the great healing potential hidden in plant preparations...
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Review ArticleThe Great Healing Potential Hidden in Plant Preparations ofAntioxidant Properties: A Return to Nature?
Małgorzata Kiełczykowska and Irena Musik
Chair and Department of Medical Chemistry, Medical University of Lublin, 4A Chodźki Street, 20-093 Lublin, Poland
Correspondence should be addressed to Małgorzata Kiełczykowska; [email protected]
Received 29 July 2020; Revised 20 August 2020; Accepted 12 September 2020; Published 10 October 2020
Academic Editor: Patricia Morales
Copyright © 2020 Małgorzata Kiełczykowska and Irena Musik. This is an open access article distributed under the CreativeCommons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided theoriginal work is properly cited.
The application of chemicals in industry and agriculture has contributed to environmental pollution and exposure of livingorganisms to harmful factors. The development of new pharmaceutical agents enabled successful therapy of various diseases, buttheir administration may be connected with side effects. Oxidative stress has been found to be involved into etiology ofnumerous diseases as well as harmful action of drugs and chemicals. For some time, plant origin substances have been studiedas potential protective agents alleviating toxicity of various substances and symptoms of diseases. The aim of the current reviewwas to present the diversity of the research performed during the last five years on animal models. The outcomes showed a hugeprotective potential inherent in plant preparations, including alleviating prooxidative processes, strengthening antioxidantdefence, ameliorating immune parameters, and reversing histopathological changes. In many cases, plant origin substances wereproved to be comparable or even better than standard drugs. Such findings let us suggest that in the future the plantpreparations could make adjuvants or a replacement for pharmaceutical agents. However, the detailed research regarding doseand way of administration as well as the per se effects needs to be performed. In many studies, the last issue was not studied,and in some cases, the deleterious effects have been observed.
1. Introduction
In the recent centuries, a great change of the conditions of thehuman life has taken place, due to the development of indus-try, agriculture, medicine, and pharmacy. The new syntheticsubstances were applied to protection of crops as well as suc-cessful therapy of various diseases. However, except for ben-eficial influence, consisting in numerous facilitations ofhuman existence and extending human life span, negativeeffects have also occurred [1, 2]. A growing pollution of nat-ural environment, resulting from the industry development,has been observed for many years [3–5]. Despite the effortsaiming at alleviating and preventing this phenomenon, it stillbelongs to the most important problems to be solved by themankind. The application of plant protection products hasmade another contribution to environmental contamination[6–9]. As it is not possible to improve the situation immedi-ately, many people, i.e., industrial workers or farmers are still
exposed to harmful substances like heavy metals [4, 10–12],organic chemicals (e.g., CCl4) [13, 14], or pesticides and plantgrowth regulators [8, 15]. Another problem results fromintroducing plenty of new pharmaceutical agents. Theyallowed to relieve suffering of many subject and successivetreatment in cases of mortal diseases. However, on the otherhand, plenty of side effects have also been observed [16, 17].Analgesic and antipyretic drugs like acetaminophen or aspi-rin can induce liver and kidney damage [18–22]. The anti-neoplastic agents can cause severe disturbances liketesticular damage [23], nephrotoxic [16, 24], cardiotoxic[25, 26], and hepatotoxic [27] effects. Antibiotics have alsoproved to show side effects including liver and kidney dam-age [28, 29]. The widespread practice of using different addi-tives to preserve and improve the taste of food makes anothersource of toxic action on human organisms [30]. The grow-ing life span is connected with an increase in incidence ofneurodegenerative disorders like Parkinson’ disease [31] or
HindawiOxidative Medicine and Cellular LongevityVolume 2020, Article ID 8163868, 55 pageshttps://doi.org/10.1155/2020/8163868
Alzheimer’s disease [32]. Furthermore, in the recent decades,obesity, hyperlipidemia, and connected disturbances havebecome a significant worldwide problem [33, 34].
All the presented facts have made the scientists searchfor any agents which could exert protective effects againsttoxic environmental pollutants and chemicals used inindustry and agriculture and replace the standard drugsor make beneficial adjuvants. The return to natural prod-ucts, sometimes used for thousands years in traditionalmedicine, has become one of the significant directions ofthis research [35–39]. It could be stated, without any exag-geration, that “a great return to nature” is recently beingobserved. Plant extracts and plant origin substances per sedo not show so many side effects as pharmacological sub-stances. On the other hand, they contain numerous com-pounds of anti-inflammatory and antioxidative propertieslike polyphenolic derivatives and flavonoids [40–42]. Thepresented facts prompted large-scale research on possibili-ties of application of plant preparations as protective agentsagainst toxicity of various substances as well as adjuvantsalleviating the symptoms of diseases, obesity, and traumata[6, 25, 38, 43–49]. A great quantity of plant species havebeen investigated, and the obtained results seem to be verypromising. Some studies have included the comparison ofthe investigated materials with standard drugs, and the out-comes suggest that in many cases the replacement would bepossible [20, 31, 35, 50–53]. However, many questionsremain to be solved as to the best way of treatment andthe most beneficial dose.
Oxidative stress—the disturbed balance between genera-tion of reactive oxygen species (ROS) and antioxidants’ levelin an organism—has been found to be involved, less or more,into the etiology of most diseases [54–56]. This processinvolves the generation of ROS, active particles capable ofinjuring all bioactive compounds—protein, lipids, andnucleic acids in an organism. Lipid peroxidation caused byROS may lead to damage of membrane lipids. Living organ-isms developed a wide range of endogenous substances, bothenzymatic and low-molecular ones, which can neutralizeROS. Negative effects resulting from stress, exposure totoxic substances, side effects of the standard drugs, or evenfood supplements have also been proved connected withprooxidative processes and deterioration of antioxidantdefence [13, 30, 40, 57, 58]. Plant origin preparations, inturn, have been found to exert a strong antioxidant actiondue to high content of components of antioxidative proper-ties. Numerous studies have revealed their direct influenceon oxidative processes by reducing lipid peroxidation orprotein carbonylation as well as increase in antioxidantenzymes’ activities and low-molecular antioxidant concen-trations [34, 43, 59, 60].
Different pathways involved in oxidative and inflamma-tory processes have been found to be affected in the courseof protective action of plant preparations.
The studies have shown the involvement of Nrf2 andKeap1 proteins. Nrf2 is regarded as a key transcription factormediating the endogenous antioxidant response, and Keap1is its negative regulator. Under oxidative stress conditions,Nrf2 is released and translocated to the nucleus where it
binds to ARE regions in DNA and stimulates antioxidantenzyme gene expression. Both Nrf2 and Keap1 as wellproteins regulated by Nrf2, responsible for defence againstantioxidant stress like HO-1 and γ-GCS, have been foundto be disturbed by harmful factors (cadmium or high-fat diet)and regulated by plant preparations [12, 61]. Plant originsubstances have been reported to cause upregulation ofNrf2, HO-1, and γ-GCS in both nonexposed and Pb-exposed rats [62].
Another pathway connected with oxidative and inflam-matory processes which have been proved involved into pro-tective properties of plant preparations is NF-κB pathway.NF-κB is a transcription factor responsible for expression ofproinflammatory cytokines [56]. Its activation can be trig-gered by TLR receptors, belonging to pattern recognitionreceptors. The inflammation and redox balance have beenfound to be strongly connected with each other [63]. Inter-leukins, γ-interferon and tumour necrosis factor, have beenfound to affect ROS production [64]. The involvement ofthe LPS-TLR4-NF-κB pathway into protective action of plantmaterials has been reported [56, 65]. Other authors havestated that a protective effect of a plant extract, resulting fromantioxidative and anti-inflammatory influence observed indiabetes animal model, could be attributed to inhibition ofNF-κB activation [66].
Mitogen-activated protein kinases (MAPK) belong toenzymes which make mediators of various processes occur-ring in cells like death, proliferation, or differentiation. TheMAPK pathway begins from a signal from an extracellularreceptor and through a cascade of subsequent protein phos-phorylation leads to activation of different proteins includingtranscription factors (e.g., p53 protein) and finally to theexpression of genes. ROS have been proven to be connectedwith particular steps of the MAPK pathway. There are threekinds of MAPK in mammals: p38 MAPK, ERK1 (extracellu-lar signal-regulated kinase 1), and JNK (c-Jun N-terminalkinase) [64, 67]. The studies on plant revealed the influenceof the studied plant materials on some elements of the MAPKpathway [42].
The next pathway connected with oxidative stress whichhas been found affected by plant preparations is the JAK/-STAT pathway. An outside signal, usually being a cytokine,binds to a membrane receptor resulting in its dimerization.The next stage is the activation of JAK which renders possiblephosphorylation of receptor, which in turn enables STATbinding and phosphorylation. Activated by phosphorylationSTAT is then translocated into the nucleus where it acts as atranscription factor [68]. The relationships between thispathway and ROS have been reported [69]. In the currentstudy, disturbances of oxidative balance as well as bone mar-row damage and reduction in pJAK2/JAK2 and pSTAT5a/S-TAT5a, caused by radiation exposure, have been found to beimproved by a plant preparation, which made the authorssuggest that the studied material can stimulate the JAK2/-STAT5a signal pathway [70].
The aim of the current review is to present the results ofthe studies performed in the last five years regarding the pro-tective and medicinal properties of plant origin preparationswith particular emphasis on their antioxidant action.
2 Oxidative Medicine and Cellular Longevity
2. The Protective Properties of PlantPreparations against Toxicity ofVarious Factors
2.1. The Protective Influence of Plant Preparations againstChemicals Applied in Agriculture. The use of different che-micals in food production has been growing dramaticallyin the recent years, causing the contamination of the natu-ral environment and increasing thread to human health.Neurotoxicity, hepatotoxicity, reproductive disturbances,and cancerogenesis belong to the negative effects exertedon organisms [6, 8, 15, 71]. Moreover, chemicals of lipo-philic character can be accumulated in membranes [9].Enhanced generation of ROS was proved involved into theirharmful influence [6, 9, 71]. Plant origin materials wererevealed to show protective properties not only by strength-ening the antioxidant barrier but also by reversing histo-pathological changes. A wide range of different materialswas studied, including simple extracts [2, 6, 7] as well ascommercial products [9, 15]. The saponins from Tribulusterrestris, which were reported to possess antiaging action,were found to exert protective effects against rotenone-induced parkinsonism [15].
The details concerning the above mentioned studies arepresented in Table 1.
2.2. The Protective Influence of Plant Preparations againstToxic Effects of Heavy Metals. Environmental pollution withheavy metals makes a great global problem. The most toxicones are lead, cadmium, and mercury. Even low concentra-tions can cause severe disturbances of organism, includingbrain, hepatic, renal, and reproductive damage [10]. As theirharmful action is connected with oxidative stress induction,plant extracts showing antioxidant properties were studiedas possible protective agents and the obtained results werefound to be promising [10, 11], although the accumulationof a toxic metal could not be prevented in every case [62].
The ability of plant origin substances proanthocyanidinsto prevent lead-induced hepatotoxicity was suggested to beconnected with the Nrf2/ARE pathway (as an increase ofmRNA expression levels of Nrf2 in the liver of mice admin-istrated with proanthocyanidins and/or lead was observed)as well as with the reduction of endoplasmatic reticulumstress via a decrease in stress-related proteins GRP78 andCHOP [62].
In the experiments concerning the toxicity of mercury,plant extracts relieved the negative effects in the case of bothan inorganic form (mercury (II) chloride) and organic one(dimethylmercury); at the same time, the beneficial influenceincluded not only oxidant and immunological parametersbut also histopathological changes [4, 72, 73].
Plant extracts were also found to exert wide protectiveeffects against the third most dangerous heavy metal cad-mium, with the results being confirmed by in vitro studieswith using murine hepatocytes [3]. Additionally, an animalstudy showed the involvement of the Nrf2/Keap1 pathwayinto the protective action of Pyrantha fortuneana extract asthe plant material, given both alone and coadministered withcadmium caused a significant increase in expression of Nrf2
and decrease in expression of Keap1 in the kidneys of ratsvs. the control and Cd-exposed group, respectively [12].
Apart from lead, mercury, and cadmium the researchconcerning metals’ toxicity included also liver injury causedby iron overload. 70% methanol extract of Droseraburmannii Vahl. showed a distinct, dose-dependent efficacyagainst iron-induced hepatoxicity. This effect, particularlyin case of the highest dose, was comparable with that exertedby a standard drug desirox—an iron chelator. Additionally,the studied extract studied in vitro showed the ability to che-late Fe2+ ions. Such findings made the authors suggest thatthe studied preparation might be used as a medicine in cureof iron overload-induced diseases [50].
The details concerning the above-mentioned studies arepresented in Table 2.
2.3. The Protective Influence of Plant Preparations againstVarious Chemicals. Plant origin substances, extracts andtheir particular fractions, essential oils, and seed powderswere found to reverse or alleviate disturbances of organismresulting from exposure to different chemicals. The resentresearch included various compounds, e.g., hepatotoxic tet-rachloromethane (CCl4) used for years as a solvent andnow regarded as an environmental pollutant [14], alumin-ium known for its neurotoxicity [74], aflatoxins producedby toxigenic fungi which made food contaminants [75],and chemicals used in industry and laboratory experimentslike thioacetamide [76] or 1-chloro-2,4-dinitrobenzene[77]. Additionally, plant origin substances were proved todecrease mouse mortality resulting from the acute CCl4 tox-icity [78] as well as from Concanavalin A exposure [79]. Fur-thermore, several studies included the influence of plantmaterials alone, and generally, no harmful effects wereobserved [14, 54, 74, 75, 78, 80, 81].
The details of the performed studies are presented inTable 3.
2.4. The Protective Influence of Plant Preparations againstCarcinogens. Plant extracts were studied using animal modelas for their possible application in tumour therapy due to thepresence of anticancer and antioxidant components. Thenecessity of searching for new agents, suitable for tumourtreatment, was challenged by the lack of effective chemother-apy and severe side effects associated with the used medi-cines. The obtained results seem to be promising as thestudied materials alleviated carcinogen-induced oxidativestress as well as disturbances of immunological parameters[47, 88, 89]. Histolopathological studies confirmed the bene-ficial effects of the investigated preparations [46, 89].
The detailed results of the performed studies are pre-sented in Table 4.
2.5. The Protective Influence of Plant Preparations againstEthanol. Alcohol excessive consumption and addiction leadsto different negative effects: liver injuries including steatosis[56, 91], brain damage [92], and reproductive system damage[93]. The disturbances of oxidative balance were suggested tobe one of the factors underlying alcohol toxicity, which wasconfirmed by intensification of lipid peroxidation as well as
3Oxidative Medicine and Cellular Longevity
Table1:The
protective
prop
erties
ofplantextractsagainsttoxicity
ofsubstances
appliedin
agricultu
re.
Reference
Plant
preparation,
dose,w
ayandtimeof
treatm
ent,
anim
als
The
toxicsubstance,do
se,w
ayand
timeof
expo
sure,and
negative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plantperse
Chaâbaneetal.
[6]
Nitrariaretusa
fruitaqueou
sextract
Pretreatm
entfor6days
andtreatm
entdu
ring
pencon
azoleexpo
sure
300mg/kg
b.w.,p.o.,d
aily
MaleWistarratsabou
t250g
Afungicidepencon
azole-indu
ced
kidn
eyinjury
67mg/kg
b.w.(1/30
LD50)i.p.,every
2days
from
7thun
til15thday
Plasm
a:GGT,A
LP↓;CR,u
rea,UA,L
DH
↑
Urine:volum
e↑,CR,u
rea,UA↓
Kidney:LD
H,M
DA,H
2O2,PC,
AOPP,N
P-SH,
GSH
,MT,C
AT,SOD,G
Px↑
Kidney:enlarged
Bow
man’sspace,
necrosisof
theepithelial
cells
liningthetubu
les,infiltrationof
leucocytes,glomeruli
fragmentation
↑
Plasm
a:ALP
(+),urea,L
DH,G
GT(++),
CR,U
A(+++)
Urea:UA(+),volume,CR,u
rea(++)
Kidney:LD
H,M
DA,H
2O2,PC,
AOPP,N
P-SH,
GSH
,CAT,SOD,G
Px(++),MT(+++)
Kidney:necrosisof
theepithelial
cells
liningthetubu
les(++),
enlarged
Bow
man’sspace,
infiltrationof
leucocytes,glomeruli
fragmentation
(+++)
Plasm
a:urea,L
DH
↑Urine:volum
e↑,CR,
urea
↓
Alzahrani
etal.
[15]
Standardized
Tribu
lusTerrestris
extracttablets
1000
mg(m
in.45%
sapo
nins)
Now
SportsCo.(U
SA)
5or
10mg/kg
daily,p
.o.,
for17
days
MaleSw
issalbino
mice,
20-28g
Apesticideroteno
ne-ind
uced
parkinsonism
,
nine
dosesof
1mg/kg
giveneach
48±2h
,s.c.
Activityindex(18thday)
↓
Substantianigra:%
ofpycnoticneuron
s↑,
%of
viableneuron
s↓
Striatum
:relativeexpression
ofiNOS,
COX-2
andMTH
1,MDA,8-O
H-dG↑,
dopamine,GSH
,SOD,C
AT↓
Activityindex(18thday)
(+5,+++10)
Substantianigra:%
ofviableneuron
s
(+50,+
++10),
%of
pycnoticneuron
s
(++5,+++10)
Striatum
:GSH
,SOD,M
DA(0
5,++10),
CAT
(05,+++10),do
pamine(+
5,++10),
relative
expression
ofCOX-2
andiNOS
(++both
doses),
8-OH-dGandrelative
expression
ofMTH
1
(++5,+++10)
Non
e
Selm
ietal.[71]
Lavand
ulastoechas
essentialo
ils50
mg/kg
b.w.,p.o.,for
30days
Malemice,
8-weekold,
25-30g
Malathion
(apesticide)
200mg/kg
b.w./d
ayfor30
days,p
.o.
Serum:T
↓
Testis:relative
weight,MDA,H
2O2↑,
-SH
grou
ps,G
Px,CAT,SODtotal,
Cu/Zn-SO
D,
Mn-SO
D↓
Epididymis:relativeweight,MDA,
H2O
2↑,-SH
grou
ps,G
Px,CAT,
Serum:T
(+++)
Testis:Mn-SO
D(0),-SH
grou
ps,
SODtotal(++),
relative
weight,MDA,H
2O2,GPx,
Cu/Zn-SO
D,C
AT(+++)
Epididymis:C
ATandH
2O2(++),
relative
weight,MDA,-SH
grou
ps,G
Px,
SODtotal,Cu/Zn-SO
D,M
n-SO
D(+++)
Testis:CAT↑
4 Oxidative Medicine and Cellular Longevity
Table1:Con
tinu
ed.
Reference
Plant
preparation,
dose,w
ayandtimeof
treatm
ent,
anim
als
The
toxicsubstance,do
se,w
ayand
timeof
expo
sure,and
negative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plantperse
SODtotal,
Cu/Zn-SO
D,M
n-SO
D↓
ElA
rem
etal.[7]
Phoenixdactylifera
L.datepalm
fruit
aqueou
sextract
4mL/kg
daily,p
.o.,
for2mon
ths
MaleWistarrats180–200g
Dichloroaceticacid
(afungicide)
0.5g/Lor
2g/Las
drinking
water,
for2mon
ths
0.5g/L:
Weight:testes,epididymis↓
Plasm
a:T,F
SH,L
H↓
Testes:CAT,SOD,L
PO
↑,GSH
↓2g/L:
Weight:testes,epididymis↓
Plasm
a:T,F
SH,L
H↓
Testes:CAT,SOD,L
PO
↑,GSH
,GPx↓
0.5g/Lof
dichloroaceticacid:
Weight:testes,epididymis(+++)
Plasm
a:T,F
SH,L
H(+++)
Testes:CAT,SOD,L
PO,G
SH(+++)
2g/Lof
dichloroaceticacid:
Weight:testes
(++),epididym
is(+++)
Plasm
a:T,F
SH,L
H(++)
Testes:CAT,SOD,G
SH,L
PO
(++),
GPx(+++)
Non
e
Mossa
etal.[9]
Vitisvinifera
grapepo
mace(ElK
room
Com
pany,A
lexand
ria,Egypt)
80%
ethano
licextract
100or
200mg/kg
b.w.,p.o.,28
consecutivedays
Weanlingfemaleratsabou
t50
g
Cypermethrin
(aninsecticide)
25mg/kg
b.w.(1/10
ofLD
50),p.o.,for
28consecutivedays
Relativeweight:liver
↓,kidn
ey↑
Serum:T
P,A
LB↓,AST
,ALT
,ALP
,GGT,
urea
nitrogen,C
R↑
Liver:Kup
ffer
cellactivation
,portal
infiltrationwithinflam
matorycells,
hyperplasiaof
biledu
ct,con
gestion
ofcentralveinandhepaticsinu
soids↑
Kidney:vacuolizationof
endo
thelial
liningglom
erular
tuft,vacuo
lization
ofepithelialliningrenaltub
ules,
necrosisof
epithelial↑
Relativeweight:liver,kidney
(+++both
doses);
Serum:A
LT,C
R(++both
doses),A
ST,
ALP
,GGT,T
P(++100,+++200),A
LB,u
rea
nitrogen
(+++both
doses)
Liver:Kup
ffer
cellactivation
(+100,++
200),
portalinfiltration
withinflam
matory
cells,
hyperplasiaof
biledu
ct,con
gestionof
centralveinandhepaticsinu
soids
(+++both
doses)
Kidney:vacuolizationof
endo
thelial
liningglom
erular
tuft(++100,+++200),
vacuolizationof
epitheliallining
renaltub
ules,
necrosisof
epithelial(+++both
doses)
Bothdo
ses:
Liver:Kup
ffer
cell
activation
↑
Mirzaeietal.[2]
Quercus
bran
tii7
0%ethano
lextractof
internal
layerof
thefruit
500mg/kg,p
.o.,for9days
MaleWistaralbino
rats,150-200
g
Carbend
azim
:methyl-2-benzim
idazolecarbam
ate
(afungicideagent),50mg/kg
p.o.,for
9days
Serum:A
LT,A
ST,A
LP,u
reanitrogen,C
R↑
Liver:MDA↑,GSH
↓Kidney:MDA↑,GSH
↓
Serum:A
LT,A
ST,A
LP,u
reanitrogen,
CR(++)
Liver:MDA(+),GSH
(++)
Kidney:MDA,G
SH(++)
Not
stud
ied
5Oxidative Medicine and Cellular Longevity
Table1:Con
tinu
ed.
Reference
Plant
preparation,
dose,w
ayandtimeof
treatm
ent,
anim
als
The
toxicsubstance,do
se,w
ayand
timeof
expo
sure,and
negative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plantperse
Khalafetal.[8]
Punica
gran
atum
L.po
megranatepeel
methano
lextract
250mg/kg
daily,i.g.,
for4weeks
MaleWistarrats,140-160
g
Gibberellicacid-3
(aplantgrow
thregulator)
20mg/kg
i.g.,daily
for4weeks
Testes:area
percentof
androgen
receptor
immun
oreaction,
SOD,C
AT↓
Testes:area
percento
fand
rogenreceptor
immun
oreaction,
SOD,C
AT(+++)
Non
e
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(+):aslight
beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no
beneficialeffect.
6 Oxidative Medicine and Cellular Longevity
Table2:The
protective
effectsof
plantorigin
substances
againsttoxicity
ofheavymetals.
Reference
Plant
preparation,
dose,w
ayand
timeof
treatm
ent,anim
als
The
toxicsubstance,do
se,w
ayandtimeof
expo
sure,
andnegative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plant
perse
Abd
elMon
eim
[10]
Indigofera
oblongifo
lialeaves
water-m
ethano
l(1:2)extract
100mg/kg
b.w.p
.o.d
aily,1
hbefore
Pbfor5days
MaleWistarrats,8-w
eek-old,
150–180g
Pblead
acetateacutetoxicity,20mg/kg
b.w.d
ailyfor5days,i.p.
Serum:A
ST,A
LT,A
LP,totalbilirub
in,T
C,
TG,L
DL-c↑,HDL-c↓
Liver:relative
weight,Pbaccumulation,
LPO,
NO
andH
2O2,↑,GSH
,SOD,C
AT,G
Px,GR↓
Liver:expression
ofmRNAof
SOD2,CAT,
GPxandBcl-2↓,Bax
andHO-1↑
Serum:A
LP,totalbilirub
in,T
G,H
DL-c(++),AST
,ALT
,TC,L
DL-c(+++)
Liver:relative
weight,Pbaccumulation,
NO,H
2O2,
SOD,C
AT,G
R(++),LP
O,G
SH,G
Px(+++)
Liver:HO-1(-),expression
ofmRNAof
SOD2,CAT,
GPx,Bax,B
cl-2
(++)
Liver:GSH
,GPx↑
Long
etal.[62]
Proanthocyanidins
extractedfrom
grapeseeds(ZelangMedical
Techn
ologyCom
pany,
Nanjin
g,China)
100mg/kg
b.w.,p.o.,sixdays
every
weekfor6weeks
MaleKun
mingmice,3-week-old
Pblead
acetate0.2%
indrinking
water
for6weeks
Blood
:Pb↑
Serum:A
LT,A
ST,A
LP↑
Liver:GSH
,GPxandSO
D↓,relative
mRNA
expression
ofNrf2,γ-GCS,HO-1
slightly↑,Pband
MDAas
wellasrelative
mRNAexpression
ofBax,
GRP78
andCHOP↑,relative
mRNA
expression
ofBcl-2
↓
Blood
:Pb(0)
Serum:A
LT,A
ST,A
LP(++)
Liver:Pb(+),GPx,SO
D,relativemRNAexpression
ofBax,B
cl-2
GRP78,C
HOP(++),MDA,G
SH(+++),
relative
mRNAexpression
ofNrf2,γ-GCS,HO-1
↑
Liver:relative
mRNA
expression
ofNrf2,γ-GCS,
HO-1
↑
El-Boshy
etal.[11]
Thymus
vulgarisleafethano
lextract
500mg/kg/day,p
.o.,for6weeks
Sprague-Daw
leymalerats,
abou
t150g
Pblead
acetate500mg/Lin
drinking
water,for
6weeks
Serum:T
NF-α,IL-1β
,IL-6↑,IN
F-γ,IL-10↓
Liver:Pb,MDA↑,GSH
,GPx,CAT↓
Kidney:Pb,MDA↑,GSH
,GPx,CAT↓
Serum:IL-1β
,IL-6(++),IN
F-γandIL-10(+++)
Liver:Pb(++),MDA,G
SH,G
Px,CAT(+++)
Kidney:Pb(++),MDA,G
SH,G
Px,CAT(+++)
Serum:IL-10
↑Liver:GSH
,GPx↑
Kidney:GSH
,GPx↑
Dua
etal.[3]
Ipom
oeaaqua
tica
andEn
hydra
fluctuan
saerialpartsaqueou
sextracts
Pretreatm
ent
100mg/kg
b.w.,p.o.,for
5days
followed
bycadm
ium
chloride
Swissmalealbino
mice,1-2
mon
ths,20-30g
Cdcadm
ium
chloride,4
mg/kg
b.w.,for6days,
once
daily,p
.o.
Blood
:RBC,H
GB↓
Serum:A
LT,A
ST,u
rea,TC,T
G↑,HDL-c↓
Liver:cadm
ium,R
OS,LP
O,N
ADH
oxidase,protein
carbon
ylation↑,totalcoenzym
esQ9andQ10,C
AT,
SOD,G
ST,G
Px,GR,G
6PD,G
SH↓
Kidney:cadm
ium,R
OS,LP
O,N
ADHoxidase,protein
carbon
ylation↑,totalcoenzym
esQ9andQ10,C
AT,
SOD,G
ST,G
Px,GR,G
6PD,G
SH↓
Heart:cadmium,R
OS,LP
O,N
ADH
oxidase,protein
carbon
ylation↑,totalcoenzym
esQ9andQ10,C
AT,
SOD,G
ST,G
Px,GR,G
6PD,G
SH↓
Brain:cadmium,R
OS,LP
O,N
ADH
oxidase,protein
carbon
ylation↑,totalcoenzym
esQ9andQ10,C
AT,
SOD,G
ST,G
Px,GR,G
6PD,G
SH↓
Testes:cadm
ium,R
OS,LP
O,N
ADH
oxidase,protein
carbon
ylation↑,totalcoenzym
esQ9andQ10,C
AT,
SOD,G
ST,G
Px,GR,G
6PD,G
SH↓
Bothextracts:
Blood
:RBC,H
GB(++)
Serum:A
LTAST
,urea,TC,T
G,H
DL-c(++)
Bothextracts:
Cadmium
burden,R
OS,G6P
D,N
ADPH
oxidase:
liver,kidney,heart,brain,
testes
(++)
LPO:liver,kidney,heart,brain,
testes
(+++);
Protein
carbon
ylation:liver,kidney,heart,testes(++),
brain(+++)
TotalcoenzymeQ9:liver,brain,h
eart,testes(++),
kidn
ey(+++)
TotalcoenzymeQ10:kidney,brain,
testes
(++),liver,
heart(+++)
CAT:liver,brain,h
eart(++),kidn
ey,testes(+++)
SOD,G
ST:liver,kidney,heart,brain,
testes
(+++)
GPx:liver,h
eart,testes(++),brain,
kidn
ey(+++)
GR:h
eart,testes,brain(++),liver,kidney(+++)
GSH
:heart,kidney,brain(++),liver,testes(+++)
Not
stud
ied
7Oxidative Medicine and Cellular Longevity
Table2:Con
tinu
ed.
Reference
Plant
preparation,
dose,w
ayand
timeof
treatm
ent,anim
als
The
toxicsubstance,do
se,w
ayandtimeof
expo
sure,
andnegative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plant
perse
Olaniyan
etal.[1]
Plukenetia
conophoraseeds
methano
lextract
100or
200mg/kg
b.w.,p.o.,for
54days
afterCdC
l 2treatm
ent
MaleWistarrats,150-190
g
Cdcadm
ium
chloride,a
singledo
se2mg/kg
b.w.,i.p.
Serum:T
,LH,F
SH↓
Epididymalsemen:cou
ntof
cells,m
otility,viability↓
Testis:MDAandNO
↑,SO
D,C
AT,G
Px,GST
,Na+/K
+ATPase,Ca2
+ATPase,Mg2
+ATPase↓
Epididymis:M
DAandNO↑,SO
D,C
AT,G
Px,GST
↓
Serum:L
H(0
100,+200),F
SH(+
both
doses),
testosterone
(++100,+++200)
Epididymalsemen:cou
ntof
cells,m
otility,
viability
(++both
doses)
Testis:Mg2
+ATPase(++both
doses),N
a+/K
+ATPase
(++100,+++200),M
DA,N
O,SOD,C
AT,G
ST(+++both
doses),C
a2+ATPase(+++100,↑200),
GPx(↑
both
doses)
Epididymis:G
Px(+
both
doses),SOD,G
ST,
Na+/K
+ATPaseandCa2
+ATPase(++both
doses),
CAT(++100,+++200),M
DA,M
g2+ATPase
(+++bo
thdo
ses),N
O(+++100,↓200)
Not
stud
ied
Mężyń
ska
etal.[5]
Aroniamelan
ocarpa
L.berries
extract(A
damed
Con
sumer
Health
care,T
uszyn,
Poland)
0.1%
aqueou
ssolution
inform
oftheon
lydrinking
fluidfor3,10,17
or24
mon
ths
FemaleWistarrats,3-4-w
eek-old
Cdcadm
ium
chloride
indiet1mg/kg
(Cd 1)or
5mg/kg
(Cd 5)for3,10,17or
24mon
ths
Liver:SO
D(Cd 1
3,10,17m)and(Cd 5
17m)↓;CAT
(Cd 5
17m)↓;
GPx(Cd 1
3,10,17,24
m),(Cd 5
3,10,17,24
m)↓;GR
(Cd 1
10,24m),(Cd 5
10,17m)↓;GST
(Cd 1
3,10,
17m),(Cd 5
3,10,17m)↓;GSH
/GSSG(Cd 1
17m),
(Cd 5
10,17m)↓;H
2O2(Cd 1
10,17,24
m),(Cd 5
10,
17,24m)↑;OSI
(Cd 1
10,17m),(Cd 5
3,10,17,24
m)
↑;MDA(Cd 1
10,17,24
m),(Cd 5
10,17,24
m)↑
Liver:SO
D:C
d 1(+
3m,0
10m,+
++17
m),
Cd 5
(+++17
m)
CAT:C
d 5(++17
m)
GPx:Cd 1
(+++3,10
m,+
+17,24m),
Cd 5
(03m,+
+10
and17
m,+
++24
m)↓
GR:C
d 1(+++10
m,↑
24m),
Cd 5
(++1m,-
17m)
GST
:Cd 1
(+++3,10,17m),Cd 5
(++3m,0
10m,+
++17
m)
GSH
/GSSG:C
d 1(+++1m),Cd 5
(+++10
m,↑
17m)
H2O
2;Cd 1
(+++10,17,24
m),Cd 5
(+++10,17,24
m)
OSI:C
d 1(+++10,17m),Cd 5
(+++3,10,17,24
m)
MDA:C
d 1(+++10,17,24
m),Cd 5
(+++10,17,24
m)
Liver:CAT10m
↓,GR3m
↓,GSH
/GSSG
24m
↑
Keetal.[12]
Pyracantha
fortun
eana
fruits60%
ethano
lextract
Pretreatm
ent,1hbeforecadm
ium,
250mg/kg,p
.o.,for5days
MaleWistarrats,7-8-w
eek-old,
150-170g
Cdcadm
ium
chloride,6.5mg/kg
daily
for5days,i.p.,
Bod
yweightgain
↓Kidneyweight↑
Plasm
a:UA,u
reaandCR↑
Kidney:Cdaccumulation,
MDA,N
O,expressionof
Keap1,B
axandTNF-αprotein↑,CAT,G
Px,GSH
,SO
D,G
R,expressionof
Bcl-2,H
O-1,γ-G
CS,NQO1
andNrf2protein↓
Bod
yweightgain
(++)
Kidneyweight:(++)
Plasm
a:urea,U
AandCR(++)
Kidney:Cdaccumulation,
MDA,N
O,C
AT,G
Px,
GSH
,SOD,G
R(++),expression
ofBcl-2,B
axand
TNF-αprotein(++),expression
ofKeap1,H
O-1,γ-
GCS,NQO1andNrf2protein↑
Kidney:
expression
ofKeap1,H
O-1,γ-
GCS,NQO1,
Nrf2↑
Kim
etal.[73]
Dendropan
axmorbifera
leaf80%
ethano
lextract
100mg/kg,p
.o.,daily
for4weeks
MaleSprague-Daw
leyrats,
7-week-old
Hgdimethylm
ercury
daily
5μg/kg,i.p.,for4weeks
Hippo
campu
s:Hgconcentration,
ROSprod
uction
,GST
,MDA↑,SO
D1,totalsulfhydrylcon
tent,
CAT,G
Px,GR↓
Hippo
campu
s:CAT,totalsulfh
ydrylcon
tent
(+),
Hgconcentration,
ROSprod
uction
,MDA,
SOD1,GST
,GPx,GR(++)
Non
e
8 Oxidative Medicine and Cellular Longevity
Table2:Con
tinu
ed.
Reference
Plant
preparation,
dose,w
ayand
timeof
treatm
ent,anim
als
The
toxicsubstance,do
se,w
ayandtimeof
expo
sure,
andnegative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plant
perse
Jahanetal.[72]
Chenopodium
albu
mLinn
.seed
ethano
lextract
200mg/kg
b.w.,p.o.,for
30days
Sprague-Daw
leymalerats,
abou
t240g
Hgmercury(II)chloride,0.15mg/kg
b.w.for
30days,i.p.
Bod
yweight↓
Plasm
a:BUN,C
R,cho
lesterol,T
G,L
DL↑,HDL,
T↓
Testiculartissue:T
P,C
AT,SOD,G
ST↓,
ROSandTBARS↑
Dailysperm
prod
uction
:↓
Bod
yweight(+++)
Plasm
a:cholesterol,TG(-),LD
L,CRand
HDL(++),BUN
andT(+++)
Testiculartissue:T
P,C
AT,SOD,G
ST,
ROSandTBARS(++)
Dailysperm
prod
uction
:(+++)
Non
e
Gao
etal.[4]
Rheum
palm
atum
L.driedroot
andRhizoma(Lixian
Pharm
aceuticalsCom
pany,
Longnan,
China)60%
ethano
lextract
1200
mg/kg,i.g.,daily
for7days
Sprague-Daw
leymalerats,
140–160g
Hgmercury(II)chloride,a
singledo
seof
2mg/kg,s.c.,on
the5thday
Bod
yweight:↓
Serum:T
P,A
LB↓BUN,C
R↑
Kidney:GSH
,GPxandCAT↓
Renaltubu
leepithelialcells:swellin
g,necrosis,
granular
degeneration
,interstitial
vascular
congestion
↑
Bod
yweight:(++)
Serum:A
LB,C
R,B
UN
(++);TP(+++)
Kidney:GPx,CAT(0),GSH
(+)
Renaltubu
leepithelialcells:swellin
g(+),
necrosisgranular
degeneration
,interstitial
vascular
congestion
(++)
Not
stud
ied
Ghateetal.[50]
Drosera
burm
anniiV
ahl.70%
methano
lextract
50,100,or200mg/kg
b.w.,p.o.,for
21days
from
thenext
dayafter
firstinjectionof
iron
dextran
MaleSw
issmice,
20g
Iron
-dextran
100mg/kg
b.w.,i.p.,
five
doses(one
dose
everytwodays)
Serum:A
LT,A
ST,A
LP,bilirubin,
ferritin
↑Liver:SO
D,C
AT,G
ST,G
SH↓,LP
O↑
Serum:bilirubin(+
50,+
+100+++200),
ALT
andAST
(++alld
oses),ALP
and
ferritin
(++50
and100,+++200)
Liver:SO
D(0
50,+
+100,+++200);C
AT,
GST
,and
LPO
(+++alld
oses);
GSH
(050,+
+100and200)
Not
stud
ied
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(+):aslight
beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no
beneficialeffect;(-):intensification
oftheharm
fuleffect.
9Oxidative Medicine and Cellular Longevity
Table3:The
protective
effectsof
plantpreparations
againsttoxicity
ofdifferentchem
icals.
Reference
Plant
preparation,
dose,w
ayandtimeof
treatm
ent,
andanim
als
The
toxicsubstance,do
se,w
ayandtime
ofexpo
sure,and
negative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plantperse
AlSaidetal.[13]
Pipercubeba
fruits
70%
ethano
lextract
Pretreatm
ent250or
500mg/kg
for7days,p
.o.
MaleWistaralbino
rats180–200g
CCl 4-ind
uced
hepatotoxicity,a
singledo
seof
0.4mL/kg,i.p.
Serum:A
LT,A
ST,G
GT,A
LP,bilirubin,
LDH
↑Liver:MDA↑,NP-SH,C
AT,T
P↓
Liver:mRNAexpression
ofTNF-α,IL-6,IL-10,HO-1,
iNOS↑
Serum:A
LT,A
ST,L
DH
(0250,++500),
GGT(+
250,++500),A
LP,bilirubin
(++both
doses)
Liver:TP(0
250,++500),M
DA,C
AT
(+250,++500),N
P-SH
(++250,+++500)
Liver:mRNAexpression
ofIL-10(↑
both
doses),
TNF-α,IL-6,HO-1,iNOS(++)
Not
stud
ied
Bellassou
edetal.[14]
Menthapiperita
L.leaf
essentialo
ilPretreatm
ent
5,15,and
40mg/kg
b.w.,daily
for7days,p
.o.
MaleWistarrats
200–220g
CCl 4:1
mL/kg
b.w.onthe7thday,i.p.
Serum:A
LT,A
ST,A
LP,L
DH,G
GT,T
C,T
G,L
DL,
urea,C
R↑,HDL↓
Liver:LP
O,infl
ammatorycells
andcellu
larnecrosis↑,
SOD,C
AT,G
Px↓
Kidney:LP
O,glomerular
andepithelialcellsof
the
proxim
altubu
lesnecrosis↑,SO
D,C
AT,G
Px↓
Serum:A
LT,A
ST,A
LP,LDH,G
GT,T
C,T
G,H
DL,
LDL,
urea,C
R(+
5,++15,40)
Liver:inflam
matorycells
andcellu
larnecrosis,LPO,
SOD,C
AT,G
Px(+
5,++15,and
40)
Kidney:LP
O,SOD,C
AT,G
Px,glom
erular
and
epithelialcellsof
theproxim
altubu
lesnecrosis(+
5,++15,and
40)
40mg/kg
b.w.only
stud
ied:
none
Simeono
vaetal.[54]
Astragalusmonspessulanu
sL.
n-bu
tano
lic
extract—
obtained
bysuccessive
extraction
of80%
methano
lextractwithCH
2Cl 2,ethylacetate,
andn-bu
tano
l
Pretreatm
ent
100mg/kg,for
7days,p
.o.
MaleWistarrats
200–220g
CCl 4-ind
uced
hepatotoxicity
asingledo
se1.25
mL/kg
of10%
CCl 4in
oliveoil
Serum:A
LT,A
ST,A
LP↑
Liver:MDA↑,GSH
,CAT,SOD,
GPx,GR,G
ST↓
Serum:A
LT,A
ST,A
LP(+++)
Liver:GR,G
SH,C
AT,G
Px,GST
(++),
MDA,SOD
(+++)
Non
e
Shah
etal.[80]
Com
melinanu
difloraL.
methano
lextract
Pretreatm
entfor12
days
and2-day-treatm
ent
150,300,450mg/kg
b.w.,p.o.
MaleSpragueDaw
leyrats,150–250
g
CCl 41.0mL/kg
b.w.,twodo
seson
13thand14
thdays
Serum:A
LT,A
ST↑
Liver:GSH
,GST
,GPx,GR,C
AT,G
6PD,Q
R↓,LP
O,
HNE-m
odified
proteinaddu
cts,8-OHdG
,TNF-α,IL-
6,PGE2↑
Serum:A
LT,A
ST(++alld
oses)
Liver:GSH
,GST
,GR,C
AT,G
6PD,
QR,L
PO,H
NE-m
odified
proteinaddu
cts,
8-OHdG
,TNF-α,IL-6,PGE2(++alld
oses),
GPx(++150,+++300,450)
450mg/kg
b.w.only
stud
ied:
none
Yoshiokaetal.[78]
Sasa
veitchiileafextract
Pretreatm
ent0.2mL(1
mLmadefrom
2.82
gof
leaves)for7days
once
perday,p.o.
Maledd
Ymice,7weeks
CCl 43g/kg
asingleinjection,
i.p.
Plasm
a:ALT
,AST
,BUN,C
R↑
Liver:MDA,C
a↑
Kidney:MDA↑
Plasm
a:ALT
,AST
,BUN
(++),
CR(+++)
Liver:MDA,C
a(++)
Kidney:MDA(+)
Non
e
10 Oxidative Medicine and Cellular Longevity
Table3:Con
tinu
ed.
Reference
Plant
preparation,
dose,w
ayandtimeof
treatm
ent,
andanim
als
The
toxicsubstance,do
se,w
ayandtime
ofexpo
sure,and
negative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plantperse
Linetal.[82]
Chenopodium
form
osan
umKoidz
(red
quinoa):
who
leseed
powder,50%
ethano
licbran
extract,
aqueou
sbran
extract
5.13
g/kg
ofredqu
inoa
who
leseed
powder
(rutin
8.46
mg/kg/day),p.o.
1.54
g/kg
ofredqu
inoa
bran
50%
ethano
lextract(rutin
16.4mg/kg/day),p.o.
1.54
g/kg
ofredqu
inoa
bran
water
extract
(rutin
3.92
mg/kg/day),p.o.
MaleBALB
/cmice
CCl 40.5mL/kg
b.w.,twotimes
weekly(Thu
rsdayand
Sund
ay)for6weeks,i.p.
Serum:A
ST,A
LT,T
P,A
LB,
globulins,bilirub
in,C
R,B
UN
↑,ALP
↓Liver:TBARS,ROS,TNF-α,T
GF-β1,
IL-6
↑,SO
D,C
AT↓
Who
leseed
powder:
Serum:A
LP(0),CR,BUN,A
LB,globu
lins(+),ALT
,TP,bilirubin(++),AST
(+++)
Liver:TBARS,ROS,TNF-α,T
GF-β1,IL-6,SOD,
CAT(+++)
Ethanol
bran
extract:
Serum:A
LP(↓),ALB
,globu
lins,BUN(+),CR,A
LT,
AST
,TP,bilirubin(++)
Liver:TGF-β1(+),ROS(++),TBARS,TNF-α,
IL-6,C
AT(+++),SO
D(↑)
Water
bran
extract:
Serum:B
UN,A
LP(0),CR,bilirubin,ALB
,globu
lins
(+),ALT
,AST
,TP(++)
Liver:CAT,T
GF-β1,ROS(+),IL-6
(++),TBARS,
TNF-α(+++),SO
D(↑)
Not
stud
ied
Parvezetal.[83]
Solanu
msurattense
leaves
70%
ethano
lextract
100and200mg/kg
b.w.,p.o.,for
3weeks
MaleWistarrats,8-9-w
eek-old,
200-220g
CCl 4in
liquidparaffin(1:1)
1.25
mL/kg
b.w.,i.p.
Serum:A
ST,A
LT,A
LP,G
GT,bilirubin,
TC,T
G,
LDL,
VLD
L↑;TPandHDL↓
Liver:MDA↑,NP-SH
↓
Serum:A
ST(0
100,+200),T
P,H
DL
(0100,++200),G
GT,L
DL,
VLD
L(+
100,++200)
ALT
,ALP
,bilirubin,
TC,
TG(++both
doses)
Liver:MDA(0
110,++200),N
P-SH
(++both
doses)
Not
stud
ied
Bahcecioglu
etal.[76]
Pistacia
terebinthu
scoffee
(coff
eebranded
“Harpu
tÇedeneCoff
ee”)
Freshlyprepared
coffee
indrinking
water
(the
contentincreasedby
25%
during
each
preparation,
reaching
upto
100%
atthe
endof
7days),for8weeks
MaleSprague-Daw
leyratsabou
t250g
Thioacetamide-indu
cedchronic
liver
injury,100
mg/kg
b.w.,i.p.,
threetimes
weeklyfor8weeks
Plasm
a:MDA↑
Liver:TNF-α,N
F-κB
,TGF-β↑
Liver:inflam
mation,
necrosis,fi
brosis↑
Plasm
a:MDA(+)
Liver:TNF-α,N
F-κB
,TGF-β(++)
Liver:inflam
mation,
necrosis,fi
brosis(++)
Liver:
TGF-β↓
Tho
maz
al.[84]
Eugeniadysentericaleafhydroalcoh
olicextract
10,100,300
mg/kg/day,p
.o.,for45
days
starting
from
the45
thdayof
AlCl 3administration
MaleSw
issmice,25-30g
AlCl 3-ind
uced
neurotoxicity
100mg/kg/day
p.o.,for
90days
Brain
cortex:M
DA↑,SO
D↓
Hippo
campu
s:MDA↑,CAT,SOD
↓Hippo
campu
sCA1area:%
ofviableneuron
s↓,%
of
necroticneuron
s↑
Brain
cortex:M
DAandSO
D(+++)alld
oses
Hippo
campu
s:CAT(0
10,+
++100and300),M
DA
andSO
D(+++alld
oses)
Hippo
campu
sCA1area:
%of
viableneuron
s(+++10,+
+100,and300),
%of
necroticneuron
s(0
10,+
+100,and300)
Not
stud
ied
Feng
etal.[74]
Defattedwalnu
tmeal(Shaanx
iSea
EcologicalA
griculture
Co.,L
td.,Shangluo
,China)
proteinhydrolysates
1g/kg
perday,for90
days,i.g.,
Malewild
-typeKun
mingmice,8weeks
Neurotoxicityindu
cedby
D-galactose200mg/kg/day,
s.c.(6
hoursafterplantmaterial),and
AlCl 3
(100
mg/kg
inthedrinking
water)for90
days
Brain:SOD,G
Px,ChA
T↓,MDA,A
chE,
TNF-α,IL-1β
↑
Brain:SOD,G
Px,ChA
T(++),
MDA,A
chE,T
NF-α,IL-1β
(+++)
Non
e
11Oxidative Medicine and Cellular Longevity
Table3:Con
tinu
ed.
Reference
Plant
preparation,
dose,w
ayandtimeof
treatm
ent,
andanim
als
The
toxicsubstance,do
se,w
ayandtime
ofexpo
sure,and
negative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plantperse
Kuk
ongviriyapan
etal.[81]
Antidesmathwaitesian
um95%
ethano
licextractof
thefruitspo
mace
100or
300mg/kg
once
daily,p
.o.
MaleSprague-Daw
leyrats,200-220
g
Nω- nitro-L-argininemethylester-ind
uced
nitricoxide
deficiency,
50mg/kg/day
indrinking
water,for
3weeks
Blood
pressure:SBP,D
BP↑
Plasm
a:MDA,P
C↑,NO3- /NO2-level↓
Carotid
artery:sup
eroxideform
ation↑
Aortictissue:eNOSproteinexpression
↓
Blood
pressure:SBP,D
BP(++both
doses)
Plasm
a:PC(0
100,+++200),M
DA,N
O3- /NO2-
level(++100,+++200)
Carotid
artery:sup
eroxideform
ation
(++100,+++200)
Aortictissue:eNOS(+
100,+++200)
Non
e
Yangetal.[77]
Rum
exjaponicusHou
tt.roots
95%
ethano
licextract
4mg/mLand8mg/mL,
topically
tothe
skin
andears,d
ailyfor3weeks
FemaleBalb/cmice,5-week-old
DNCB-(1-chloro-2,4-dinitrobenzene-)indu
ced
atop
icderm
atitis
200μLof
0.5%
DNCB(inaceton
e-oliveoilm
ixture)
tothedo
rsalskin
andear,on
days
1–3
Ear
thickn
ess↑
Lymph
nodesandspleen
weights↑
Skin:m
astcellnu
mber↑
Ear
thickn
ess:(++both
doses,abetter
effectforahigher
dose)
Weightof
lymph
nodes:(+
4,++8)
Weightof
spleen:(++both
doses)
Skin:m
astcellnu
mber(++both
doses,
abetter
effectforahigher
dose)
Not
stud
ied
Zheng
etal.[85]
Dracocephalum
heterophyllum
95%
ethano
lextract
Pretreatm
ent2hbefore
Con
canavalin
A20
mg/kg
b.w.,i.p.
FemaleBALB
/cmice,6-8-week-old
Con
canavalin
A-ind
uced
hepatitissublethald
ose
15mg/kg
b.w.,i.v.
Serum
8,16,and
24ho
ursafterCon
canavalin
A:A
LT,
AST
,IFN
-γ,T
NF-α↑
Liver:MDSC
s↓,Kup
ffer
cells
↑
Serum
8,16,and
24ho
ursafter
Con
canavalin
A:A
LT,A
ST,IFN
-γ,
TNF-α(++)
Liver:Kup
ffer
cells
(+++),MDSC
s↑
Liver:
Kup
ffer
cells
↑
BadrandNaeem
[75]
Physalisperuvian
acape
goldenberry
fruitpo
wder
20%
(w/w
)fruitpo
wderaddition
todiet,for
35days
Malealbino
rats,1
mon
th,140-150
g
AflatoxinsB1andG1
850ng/kgb.w./d
ayfor35
days
Weightgain,foodintake
↓Blood
:HGB,R
BC,P
LT↓,HCT,W
BC↑
Serum:Fe,T-A
OC,cho
lesterol↓,TG,LDL-c,HDL-c,
ALT
,AST
,ALP
,MDA↑
Liver:SO
D,C
AT↓,MDA↑
AFB
1
Weightgain
(++),food
intake
(+++)
Blood
:PLT
,HCT,W
BC,H
GB(++),RBC(+++)
Serum:M
DA(+),LD
L-c,HDL-c,Fe,cho
lesterol,T
-
AOC,T
G,A
LT,A
ST,A
LP(++)
Liver:SO
D,M
DA(++),CAT(+++)
AFG
1
Weightgain
(++),food
intake
(+++)
Blood
:PLT
,HCT,W
BC,H
GB(++),RBC(+++)
Serum:L
DL-c,HDL-c,Fe,cho
lesterol,T
G,A
LT,
AST
,ALP
,MDA(++),T-A
OC(+++)
Liver:SO
D,M
DA(++),CAT(+++)
Non
e
Xuetal.[79]
Polysaccharides
from
Morinda
officina
lisprocessed
root
(processed
root
byBeijin
gSanh
ePharm
aceuticalC
o.,L
td.)
500mg/kg
i.g.,on
ceadayfor18
days
FemaleBalb/cmice
Con
canavalin
A-ind
uced
liver
damage10
mg/kg
i.v.,
once
aweek
Weightindex:liver
andkidn
ey↑,thym
us↓
Serum:A
LTandAST
↑Liver:CAT↓,MDA↑
Weightindex:kidn
ey(0),liver
(+),
thym
us(+++)
Serum:A
LTandAST
(+++)
Liver:CAT,M
DA(+)
Not
stud
ied
12 Oxidative Medicine and Cellular Longevity
Table3:Con
tinu
ed.
Reference
Plant
preparation,
dose,w
ayandtimeof
treatm
ent,
andanim
als
The
toxicsubstance,do
se,w
ayandtime
ofexpo
sure,and
negative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plantperse
Ahm
edetal.[86]
Pulicaria
petiolarisaerialpart
methano
lextract
Pretreatm
ent50
or100mg/kg,p
.o.,
for5days
MaleSw
issalbino
mice,25-27g
LPS-indu
cedhepato-andcardiotoxicity,a
singledo
se10
mg/kg
i.p.
Serum:A
LT,A
ST,A
LP,L
DH,C
K-M
B,cTnI
↑Liver:GSH
,SOD↓,MDA,N
F-κB
,TNF-α,IL-6,
averageseverity
ofhistop
atho
logical
lesion
s↑
Heart:G
SH,SOD
↓,MDA,N
F-κB
,TNF-α,IL-6,averageseverity
ofhistop
atho
logical
lesion
s↑
Serum:A
LT,A
ST,A
LP,C
K-M
B,cTnI
(++both
doses),L
DH
(++50,+
++100)
Liver:averageseverity
ofhistop
atho
logical
lesion
s(+
50,+
+100),N
F-κB
,(++both
doses),
MDA,IL-6,TNF-α,G
SH(++50,+
++100),
SOD
(+++both
doses)
Heart:IL-6,NF-κB
,TNF-α,G
SH,SOD
(++both
doses),average
severity
ofhistop
atho
logicallesions
and
MDA(++50,+
++100)
100mg/kg
onlystud
ied:
Serum:
LDH
↓
Raish
etal.[87]
Lepidium
sativum
seed
ethano
lextract
Pretreatm
ent150and300mg/kg
p.o.,for
14days
MaleWistarrats,2-m
onth-old,180-205
g
D-G
alactosamine+LP
S-indu
cedhepatotoxicity
400mg/kg
and30
μg/kg,respectively,i.p.,on
the15
th
day
Serum:A
LT,A
LP,A
ST,bilirubin,
GGT↑
Liver:CAT,G
SH,SOD↓,MDA,M
PO,N
F-κB
9(p65)
DNAbind
ingactivity,m
RNAexpression
ofTNF-α,
IL-6,IL-10,
HO-1,iNOS↑
Serum:A
LT,A
LP,A
ST,G
GT(++both
doses),
bilirub
in(++150,+++300)
Liver:CAT(+
150,++300),G
SH,SOD,M
DA,
MPO,N
F-κB
9(p65)
DNAbind
ingactivity,m
RNA
expression
ofTNF-α,IL-6,HO-1,iNOS
(++both
doses)
Liver:expression
ofIL-10(+
150,↑300)
The
greaterthedo
sethemoredistincttheeffect
Not
stud
ied
Albrahim
and
Binobead[30]
Moringa
oleifera
leaf
water
extract
200mg/kg
b.w.,i.g.,for4weeks
Malealbino
rats,9-10weeks,110-130
g
Mon
osod
ium
glutam
ate-indu
cedhepatotoxicity,
5mg/kg
b.w.,i.g.,for4weeks
Serum:T
P,globu
lins↓,ALT
,AST
↑Liver:CAT,SOD,G
ST,G
SH↓,MDA,D
NAdamage,
expression
ofPCNAand
P53
proteins
↑
Serum:globu
lins(+),TP(++),ALT
,AST
(+++)
Liver:CAT,SOD,G
ST,G
SH,M
DA(++);DNA
damage(++),expression
ofPCNAandP53
proteins
(++)
Non
e
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(+):aslight
beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no
beneficialeffect.
13Oxidative Medicine and Cellular Longevity
Table4:The
protective
effectsof
plantpreparations
againstcarcinogens.
Reference
Plant
preparation,
dose,w
ayandtimeof
treatm
ent,
andanim
als
The
carcinogen,d
ose,way
andtimeof
expo
sure,
andnegative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plantperse
Bingületal.
[89]
Vaccinium
corymbosum
L.blueberriesho
mogenate
addedto
diet8%
(w/w
)and
givento
ratsfor16
weeks
MaleWistarrats,200-250
g
Diethylnitrosam
ine200mg/kg,i.p.,at
4th,
6thand8thweekof
theexperiment
Serum:A
LT,A
ST,L
DH
↑Liver:MDA,D
C,P
C,G
SH,G
ST↑,SO
D,
CAT,G
Px↓
Liver:relative
mRNAexpression
of
SOD,C
AT,G
Px↓,of
GST
-pi↑
Serum:A
LT(++),AST
(+++),LD
H(↓)
Liver:GPx,GSH
,GST
,SOD,C
AT(+),PC(++),
MDA(+++),DC(↓)
Liver:relative
mRNAexpression
ofSO
D,C
AT,
GPx(0),of
GST
-pi(++)
Non
e
Khanetal.
[88]
Phoenixdactylifera
L.(A
iwadates)water
extract
0.5or
1.0g/kg
b.w.,daily
for10
weeks,startingon
the
next
dayafterdiethylnitrosamine
MaleWistarrats,5-6-w
eek-old,
100-120g
Diethylnitrosam
ine-indu
cedhepatocellu
lar
carcinom
a,twodo
ses
180mg/kg
b.w.at15
days
interval,p
.o.
Serum:A
LT,A
ST,A
LP,IL-1α
,IL-1β
,GM-C
SF,
MDA↑,SO
D,G
R,G
Px,CAT,IL-2,IL-12,IL-4
↓
0.5g/kg
b.w.:
Serum:C
AT,M
DA,IL-1β
(-),IL-4
(0),IL-2
(+),
SOD,G
R,G
M-C
SF,A
LP(++),ALT
,AST
,GPx,IL-1α,IL-12
(+++)
1.0g/kg
b.w.:
Serum:IL-4,CAT(0),ALP
,MDA,
AST
,IL-1α
(↓),
SOD,G
R,IL-β,G
M-C
SF,IL-2(++),
ALT
(+++),GPx,IL-12(↑)
Not
stud
ied
Cho
ietal.
[46]
Centella
asiatica
leaf
(MartinBauer
GmbH
&Co.KG,V
estenb
ergsgreuth,
Germany)
75%
ethano
lextract
100or
200mg/kg,p
.o.,daily
for5days
followingcarcinogen
MaleSprague-Daw
leyrats,6-w
eek-old,
180-200g
Dim
ethylnitrosamine-indu
cedliver
injury
30mg/kg,i.p.
Serum:A
ST,A
LT,A
LP,totalbilirub
in,T
NF-α,IL-1β
,IL-6,
INF-γ,IL-10,IL-12,IL-2,G
M-C
SF↑
Liver:fibrosis,intralobu
lardegeneration
,focalnecrosis,
MDA↑,GPx,SO
D,C
AT↓
Serum:A
ST,INF-γ(↓
both
doses),IL-10
(++100,0200),IL-12
(++100,+200),total
bilirub
in,A
LT(+
100,++200),
ALP
(++100,+++200),
IL-12(+++100,++200),T
NF-α,IL-1β
,IL-6,
GM-C
SF(+++both
doses)
Liver:SO
D,C
ATandfibrosis(+
100,++200),
GPx(++100,+++200),intralobu
lar
degeneration
andfocaln
ecrosis(++both
doses),
MDA(+++100,↓200)
Not
stud
ied
Kiziltas
etal.
[47]
Ferulago
angulata
flow
ers80%
methano
lextract
150or
300mg/kg
b.w.,p.o.,d
aily,for
21days
MaleWistarrats,4-w
eek-old,
abou
t200g
N-N
itrosodimethylamine(dim
ethylnitrosamine)-ind
uced
oxidativestress,10mg/kg
b.w.,i.p.,forthefirst7days
Liver:SO
D,G
Px,CAT↓
Liver:SO
D(+
150,++300),
GPx,CAT(++both
doses)
Bothdo
ses:
Liver:CAT
↓
Rou
hollahi
etal.[90]
Curcumapu
rpurascens
BI.rhizom
edichloromethane
extract
250or
500mg/kg,p
.o.,on
ceadayfor
2mon
ths,afterazoxym
ethane
MaleSprague-Daw
leyrats,6
weeks,200–220
g
Azoxymethane-ind
uced
aberrant
cryptfoci
15mg/kg,s.c.,on
ceaweekfor2consecutiveweeks
Colon
:CAT,G
Px,SO
D↓,aberrant
cryptfoci
form
ationandMDA↑
Colon
:aberrantcryptfociform
ation,
MDA,C
AT(++both
doses),
GPxandSO
D(++250,+++500)
Not
stud
ied
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(+):aslight
beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no
beneficialeffect;(-):intensification
oftheharm
fuleffect.
14 Oxidative Medicine and Cellular Longevity
deterioration of antioxidant barrier, observed in animalsexposed to ethanol [44, 56, 91]. The involvement of oxidantstress into ethanol toxicity was also showed by Phunchagoet al. [92] who observed the protective influence of antioxi-dant vitamin C. The studies presented in the current reviewproved that plant materials showed a wide range of protectiveactions including ameliorating of liver markers, oxidativeparameters, and alleviation of histopathological changes[56, 91, 92]. The involvement of LPS-TRL4-NF-κB pathwaywas also been proved [56, 65].
The detailed results of the performed studies are pre-sented in Table 5.
2.6. The Protective Influence of Plant Preparations againstToxic Effects of Antipyretic and Analgesic Drugs. The applica-tion of antipyretic and analgesic drugs has been growing rap-idly in recent years. Acetaminophen, known also asparacetamol, N-acetyl-p-aminophenol or APAP, a substituteof aspirin, is one of the most often used over-the-countermedicines. However, its application can cause severe hepato-toxicity, and this fact is all the more dangerous because ofpossible overdose resulting from self-administration [18, 22,40, 95]. Another side effect, connected with paracetamolapplication, is nephrotoxicity [22, 40]. The harmful actionof acetaminophen includes oxidative stress, particularly thedepletion of GSH and protein sulfhydryl groups blocking[96]. Several studies revealed the possibility of plant extractapplication as protective adjuvants, wherein Moringaperegrine, Genista quadriflora, Teucrium polium geyrii, andCassia surattensis showed the best influence which includednot only amelioration of liver damage markers but alsoimprovement of antioxidant parameters and reduction ofthe lipid peroxidation process [19, 20, 96].
The details concerning the mentioned investigations arepresented in Table 6.
2.7. The Protective Influence of Plant Preparations againstToxic Effects of Antibiotics. Not only are antibiotics used forthe treatment of Gram-negative bacterial infection, but theyalso can cause side effects to occur [98, 99]. Gentamycinbelongs to those which are used in case of strains resistantto other antibiotics, but its application can lead to hepatoand nephrotoxicity [28]. The similar properties are shownby an antibiotic polymyxin, whose application was ceasedbecause of its nephrotoxicity, but an increased drug resis-tance of Gram-negative strains has rendered it being usedagain [99]. Oxidative stress as well as inflammation processeswas suggested to take part in the development of the men-tioned negative effects [29, 98, 99]. Materials obtained fromplants containing antioxidant components and affectingimmune functions were investigated as to their possible pro-tecting application, and the results seem to be promisingalthough they also pointed to the necessity of taking properprecautions and precise choosing the dose as in some casesthe higher dose showed a better influence [29, 98], whileother authors reported quite opposite results [28].
The details concerning the above mentioned issues arepresented in Table 7.
2.8. The Protective Influence of Plant Preparations againstToxic Effects of Anticancer Drugs. Cancer successful therapyis often a great problem because of the side effects of theapplied agents which include deterioration of reproductiveproficiency [23], nephrotoxicity [16, 100], and hepatotoxicity[37] and cardiotoxicity [26]. The results of the studies pre-sented below clearly show that the toxic action of anticancerdrugs is strongly connected with the prooxidative processes,deterioration of antioxidant barrier, and histopathologicalchanges. The extracts of different plants, used as spices anddrugs in traditional medicine for centuries, were studied fortheir protective potential [101]. Both simple extracts and par-ticular fractions [25, 26] proved their protective propertieswhich included the amelioration of the disturbed oxidantparameters. Antioxidant and antiapoptotic properties ofplant extracts were confirmed by in vitro investigationsperformed on renal tubular epithelia cells [100] and cardio-myocytes [25]. Histopathological changes were also foundto be relieved by plant materials [16, 23, 24, 26, 102].
The details concerning the above mentioned issues arepresented in Table 8.
2.9. The Protective Influence of Plant Preparations againstSide Effects of Various Drugs. Many drugs’ administration isaccompanied with numerous side effects which cause lifecomplication and may negatively influence patients’ compli-ance. These facts prompted the searching for any adjuvantsreversing or at least alleviating side effects. Recently, a grow-ing interest in plant origin substances, often those used in tra-ditional medicine, is being observed [104, 105]. The studiespresented below revealed the effectiveness of plant extractsagainst toxicity of diverse drugs: psychiatric (lithium carbon-ate), thyrostatic (Propylthiouracil), and cardiac activity stim-ulators (Isoproterenol), a contrast medium (Iodixanol), anddermatological medicine (Triamcinolone acetonide). Thenegative influence of the studied drugs often included deteri-oration of antioxidant barrier [105, 106]. The studiedpreparations showed beneficial effects, and in vitro studiesconfirmed their antioxidant potential [104, 107].
The details concerning the above mentioned issues arepresented in Table 9.
2.10. The Protective Effects of Plant Preparations Observed inAnimal Models of Different Disorders
2.10.1. The Protective Effects of Plant Preparations Observedin Arthritis. Arthritis has recently become a serious, world-wide problem as this disease is related with pain and physicaldisability, and no effective therapy except for a surgery can beapplied [49]. As the risk of it increases with age, the growingspam life contributes to the still enhancing incidence. Plantsubstances were found to prevent enhancement of the proin-flammatory cytokines like IL-1β, IL-6, and TNF-α, involvedinto osteoarthritis pathogenesis of OA. Additionally, thereduction of metalloproteinases responsible for joint damageas well as upregulation of their inhibitors—TIMPs and extra-cellular matrix components—was observed [48, 49]. Further-more, plant origin substances were reported to reverse
15Oxidative Medicine and Cellular Longevity
oxidative parameters’ disturbances, also taking part in osteo-arthritis development [55].
The detailed outcomes of the performed studies are col-lected in Table 10.
2.10.2. The Protective Effects of Plant Origin Materials inCases of Neurodegenerative Disorders. The next type of dis-orders studied with using an animal model was neurode-generative diseases. ROS have been reported to beinvolved in the development of Alzheimer’s, Huntington’s,and Parkinson’s diseases. Extracts obtained from plantsused in traditional Chinese and Ayurveda medicine, posses-sing numerous therapeutic properties and containing anti-oxidant components, were shown to exert a considerablebeneficial influence [31, 32, 39].
Traumatic brain injury, regarded as a worldwide gravechallenge being a cause of many death and disability cases,is considered to need an effective therapy. Water extractsof plant commercial products were revealed to show abeneficial influence on immunological and oxidativeparameters [38, 60].
Psychiatric disorders like anxiety or depression were alsoproved to be connected with neurodegenerative disturbancesas well as changes of immunological and oxidative parame-ters which were alleviated by plant extracts [111, 112].
The detailed outcomes of the performed studies are col-lected in Table 11.
2.10.3. The Protective Effects of Plant Origin Materials inCases of Animal Menopause Model. In menopausal women,the deficiency of sex hormones can lead to various distur-bances of organism. The research concerning hormonereplacement therapy showed that it can cause different sideeffects, so the attention was paid to nonpharmaceuticalagents, all the more because plant flavonoids were provedto possess phytoestrogen properties [114]. In the performedstudies, plant origin materials improved some elements oflipid profile and oxidative parameters deteriorated by ovari-ectomy [115]. Bone mineral density in rats was also amelio-rated, although this effect became less distinct along withlengthening of the experiment [114]. However, in some cases,the obtained results were not so distinctly beneficial [116].
The details of the performed studies are collected inTable 12.
2.10.4. The Protective Effects of Plant Origin Materials inLung Disorders. Plant origin substances were shown to pos-sess some efficacy against lung disorders, and the beneficialeffect included the improvement of oxidative and inflamma-tory parameters, morphological disturbances, and factorscontrolling extracellular matrix functions and vascularhomeostasis [117–119].
The details of the performed studies are collected inTable 13.
2.10.5. The Protective Effects of Plant Origin Materials inLipid Profile Disturbances. Lipid profile disturbance is associ-ated with severe diseases like diabetes as well as hepatic andcardiovascular disorders [120]. It is rated among the mainfactors causing disability and death [34]. Factors which were
used to induce such a condition were also found to causeintensification of prooxidative processes connected withdeterioration of antioxidant defence and DNA damage. Plantpreparations proved to display beneficial effects, althoughonly in one case per se influence was studied [120].
The detailed results of the performed studies are collectedin Table 14.
2.10.6. The Protective Effects of Plant Origin Materials inIschaemia/Reperfusion Model. Ischaemia/reperfusion dam-age is a serious problem which can occur as a consequenceof surgery, e.g., transplantation or coronary bypass, andmay lead to severe injuries, resulting among other thingsfrom increase in ROS generation. Pretreatment with plantmaterials, obtained from species used in traditional medicine,was found to be effective against prooxidative processes andhistopathological changes observed in ischaemia/reperfusionanimal model [123–126].
The detailed results of the performed studies are collectedin Table 15.
2.10.7. The Protective Effects of Plant Origin Materials inAnimal Model Diabetes. Plant origin substances wereobserved to be effective at reversing disturbances observedin the course of diabetes. A wide range of agents was studied,simple extracts, combinations of two extracts as well as an oil,banana pasta or substances separated from plant material. Agreat variety of species was investigated, including herbs,fruits, or vegetables. Many of them had been known as beinguseful in different fields of medicine, sometimes from ancienttimes [66, 127–129]. In several studies, biochemical, oxidant,and inflammatory parameters in the blood and organsincluding the lens, brain, liver, pancreas, kidney, and heartwere found considerably improved or restored by differentmaterials [42, 57, 66, 128, 129]. Histopathological investiga-tion revealed that plant preparations showed a considerableability to attenuate pancreas, kidney, and liver damageobserved in the animal model of diabetes [127, 128, 130].The beneficial influence of plant extracts on the deteriorationof sperm quality [131], diabetes-associated cataract, and ret-inopathy and an ability to suppress MAPK signal transduc-tion [42] and the amyloidogenic pathway [57] werereported. However, there are limitations of these investiga-tions as in most of them the effect of the applied plant sub-stance was not studied.
The detailed results of the performed studies are collectedin Table 16.
2.10.8. The Protective Effects of Plant Origin Materials inAnimal Model of Obesity. Plant origin preparations were alsoinvestigated as to their potential to prevent pathological pro-cesses connected with obesity. This direction seems to be ofgreat importance as obesity and related disturbances, result-ing from sedentary lifestyle as well as excessive consumption,are becoming more and more serious world problem [132,133]. Diet-induced obesity was found to be connected withdifferent disturbances of various parameters including livermarkers and lipid profile as well as inflammation, lipogene-sis, and oxidative balance. The performed research revealed
16 Oxidative Medicine and Cellular Longevity
Table5:The
protective
effectsof
plantorigin
substances
againsttoxicity
ofethano
l.
Reference
Plant
preparation,
dose,w
ayandtimeof
treatm
ent,and
anim
als
The
dose,w
ayandtimeof
expo
sure,and
negative
effects
Protectiveeffectsof
plantpreparation
Effects
ofplant
perse
Akbari
etal.[93]
Zingiberoffi
cina
leRoscoe(ginger)rhizom
ehydroalcoh
olicextract
1g/kg
ofb.w./d
,p.o.,for28
days
Sprague-Daw
leymalerats,about
220g
Ethanol4g/kg
ofb.w./d
,p.o.,for28
days
Serum:T
,SHBG,D
HEAs↓
Testes:weight,Zn,
Mg,Fe,C
u↓;SO
D,
GPx,CAT↓,MDA,tHcy
↑
Serum:T
(++),SH
BG,D
HEAs(+++)
Testes:Zn(-),Cu(+),Mg,weight,SO
D,G
Px,
CAT,M
DA,tHcy
(+++),
Fe(↑)
Serum:
T↓
Testes:
Fe↑,Zn,
Mg,Cu
↓
Phu
nchago
etal.[92]
Tiliacoratriand
raaerialpartsaqueou
sextract,
100,200or
400mg/kg
b.w.,p.o.,for
14days
after
developing
ethano
ldependenceby15-w
eek
alcoho
ltreatment
MaleWistarrats,8
weeks
Ethanol-dependencecaused
byagradual
increase
ofethano
lcon
tent
indrinking
fluidfrom
5%up
to30%,a
15-w
eek
alcoho
ltreatment
Hippo
campu
s:AChE
,MDA↑,SO
D,
CAT,G
Px↓,neuron
densityin
subregions
CA1,CA2,CA3
anddentategyrus↓
Hippo
campu
s:AChE
(+100,++200,0400),
CAT(+++100and200,++400),G
Px
(↑100and200,+++400),M
DA,SOD(++alld
oses),
neuron
densityin
subregions
CA1,CA2,
andCA3anddentategyrus
(++alld
oses)
Not
stud
ied
Liuetal.[91]
Ginseng
oligop
eptidesextractedfrom
rootsof
Pana
xginseng
C.A.M
eyer
(JilinTaigu
BiologicalE
ngineering
Co.,
Ltd.,C
hina)
Pretreatm
ent:0.0625,0.125,0.25,and0.5g/kg
b.w.,for30
days,p
.o.,
Sprague-Daw
leymalerats,180-220
g
One
dose
of50%
ethano
l7g(17.5mL)/kgb.w.,i.g.
Serum:A
LT,A
ST,T
G,A
LP,T
NF-α,IL-
6,IL-1βandLP
S↑,TC,H
DL-c,LD
L-c,
TP↓
Liver:steatosisandMDA↑,SO
D,G
SH,
GPx↓
Serum:A
LP(-lower
doses,0thehigheston
e);
LDL-c,TP(0
alld
oses),HDL-c(0
thelowestdo
se,
+otheron
es),TC(++alld
oses),TG(++lower
doses,
+++higher
ones),LP
S(+++except
for0.25
mg/kg
++),
ALT
,AST
,(+++alld
oses),TNF-α,IL-6
andIL-1β(↓
alld
oses)
Liver:steatosis(++alld
oses),GPx(+
lower
doses,+++
0.25,↑
0.5),G
SH(+
lower
doses,+++higher
ones),
MDA(+++alld
oses),SO
D(+
lower
doses,++higheston
e)
Not
stud
ied
Jung
etal.[94]
Glycyrrhiza
uralensisFisher
root
70%
ethano
lextract
100mg/kg
b.w.,p.o.,for
4weeks
MaleC57BL/6mice
Dietary
ethano
lLieber–D
eCarliliq
uiddiet—36%
ofenergy
from
ethano
l,for4weeks
Serum:T
NF-α,A
LT,A
ST↑
Liver:GSH
↓,TGandmRNAexpression
ofSrebf1,C
d36,Lp
l,Fatp4↑
Serum:T
NF-α,A
LT,A
ST(++)
Liver:TG,m
RNAexpression
ofSrebf1,C
d36
andLp
I(++),GSH
andmRNAexpression
ofFatp4(+++)
Not
stud
ied
Louetal.[65]
Lind
erae
radix(preparedslices,Z
hejiang
Tiantaishan
Wuyao
BiologicalE
ngineering
Co.,L
td.,China)extractedfrom
tubers
ofLind
eraaggregata(Sim
s)Kostern,75%
ethano
lextract
1,2or
4g/kg,i.g.,for20
days
MaleSprague-Daw
leyrats,160–180
g
50%
alcoho
l10
mL/kg
b.w.,on
ceadayfor20
days,
i.g.
Serum:A
LT,totalbilirub
in,IL-6,IL-8,
TNF-α,N
F-κB
↑Portalvein:
LPS↑
Smallintestine:expressionof
tight
junction
proteins
claudin-1and
occlud
in↓
Serum:IL-6(+
1and2,+++4),T
NF-α
(+++1,++2,04),N
F-κB
(++1,+++2,and4),
ALT
,totalbilirub
in,IL-8(+++alld
oses)
Portalvein:
LPS(+++alld
oses)
Smallintestine:expressionof
tightjunction
proteins
claudin-1(+
alld
oses)andocclud
in(+++1,++2,04)
Not
stud
ied
17Oxidative Medicine and Cellular Longevity
Table5:Con
tinu
ed.
Reference
Plant
preparation,
dose,w
ayandtimeof
treatm
ent,and
anim
als
The
dose,w
ayandtimeof
expo
sure,and
negative
effects
Protectiveeffectsof
plantpreparation
Effects
ofplant
perse
Tang
etal.[56]
Cynarascolym
usL.
(articho
ke)in
freeze-dried
powder
(HuimeiAgriculturalScience
andTechn
ology
Co.,L
td.,China)
Pretreatm
ent,1ho
urbefore
alcoho
l0.4,0.8or
1.6g/kg
b.w.,p.o.,d
ailyfor10
days
MaleInstituteof
CancerResearch,
mice,
7-week-oldabou
t25
g
Ethanol
12mL/kg
b.w.,p.o.,
daily
for10
days
Liverindex:↑
Serum:A
LT,A
ST,T
G,T
C↑
Liver:SO
D,G
SH↓,MDA↑,expression
levelofT
LR4andNF-κB
p50↑,scoreof
steatosis,inflam
mationandnecrosis↑
Liverindex:(++alld
oses)
Serum:A
LT(0
0.4,+0.8,+++1.6),TG(0
0.4,++0.8
and1.6),A
ST(+
0.4and0.8,++1.6),
TC(+
0.4,++0.8and1.6)
Liver:SO
D,G
SH(++0.4and0.8,+++1.6),M
DA(+
0.4,+++0.8,and1.6),score
ofsteatosis(+
0.4,++0.8,
and1.6),score
ofinflam
mation(+
0.4,++0.8,and1.6),
scoreof
necrosis(++alld
oses),expression
ofTLR
4(+
0.4,++0.8,+++1.6),expressionof
NF-κB
p50
(++0.4,+++0.8and1.6)
Not
stud
ied
Dogan
and
Anu
k[44]
Platan
usorientalisL.
leas
water
extract
20or
60mg/mLleafinfusion
adlibitum
,for
28days
MaleWistarrats,2
mon
thsaged,about
200g
20%ethano
lwaterad
libitum
for28
days
Serum:A
ST,A
LT,LDH,G
GT,U
A,urea
↑,cholesterol,HDL-c↓
Liver:GSH
↓,GST
,MDA↑
Erythrocytes:GST
,MDA↑
Kidney:MDA↑,SO
D,G
Px,CAT↓
Serum:G
GT(-20,++60),ALT
,urea(+
20,0
60),HDL-
c(+
both
doses),LDH(++20,+
++60),cholesterol(++
20,+
60),AST
,UA(+++both
doses)
Liver:GSH
andGST
(+both
doses),
MDA(++both
doses)
Erythrocytes:GST
(0both
doses),
MDA(++20,+
++60)
Kidney:SO
D(-20,+
60),CAT(-20,+
+60),
MDA(+++both
doses),G
Px(+++20,↑
60)
Not
stud
ied
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(+):aslight
beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no
beneficialeffect;(-):intensification
oftheharm
fuleffect.
18 Oxidative Medicine and Cellular Longevity
Table6:The
protective
effectsof
plantsubstances
againsttoxicity
ofantipyreticandanalgesicdrugs.
Reference
Plant
preparation,
dose,w
ayandtimeof
treatm
ent,andanim
als
The
nameof
drug,d
ose,way
andtimeof
expo
sure,and
negative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plant
perse
Bou
zenn
aetal.[21]
Pinu
shalepensisL.
needlesessentialo
ilPretreatm
ent,1%
(w/w
),withado
seof
1mL/kg,p
.o.,for56
days
FemaleWistarrats,150-200
g
Aspirin-ind
uced
liver
and
kidn
eydamage
600mg/kg
thrice
adayfor4days,p
.o.
Weight:body,liver,kidney↓
Serum:glucose,T
C,A
ST,A
LT,LDH,C
R,urea
↑Liver:TBARS↑,SO
D,C
AT,G
Px↓
Kidney:TBARS↑,SO
D,C
AT,G
Px↓
Weight:body,liver,kidney(+++)
Serum:glucose,T
C,A
ST,A
LT,L
DH,C
R,
urea
(+++)
Liver:TBARS,SO
D,C
AT,G
Px(+++)
Kidney:TBARS,SO
D,C
AT,G
Px(+++)
Non
e
Ahm
adand
Zeb
[18]
Trifoliu
mrepens
leaf
water
extract
11mgof
solid
weight/mL;
1,2,
or3mLof
extractperdayfor2weeks
Malealbino
miceabou
t28.6g
Acetaminop
hen-indu
cedhepatotoxicity
300mg/kg
for2weeks
Serum:T
C,T
G,L
DL-c,ALT
,AST
,ALP
,glucose↑,HDL-c↓
Blood
:RBC,H
GB,H
CT,P
LT↓,
WBC↑
Liver:TBARS↑,GSH
↓
1mL:
Serum:A
LP,glucose
(0),TC,T
G(+),HDL-c,ALT
,AST
(++),LD
L-c(+++)
Blood
:PLT
(0),HCT(+),WBC(++),RBC,H
GB(+++)
Liver:GSH
(+),TBARS(++)
2mL:
Serum:T
C(+),ALT
,AST
,ALP
,TG,H
DL-c,
glucose(++),LD
L-cholesterol(+++)
Blood
:PLT
(+),RBC,H
GB,H
CT,W
BC(+++)
Liver:GSH
,TBARS(++)
3mL:
Serum:H
DL-c(0),TC,A
ST,A
LT,A
ST(++),
glucose,LD
L-c(+++)
Blood
:PLT
,RBC,H
GB,H
CT,W
BC(+++)
Liver:TBARS,GSH
(++)
Stud
iedon
lyfor
the1mLdo
seSerum:T
C↓,
HDL-c↑
Azim
etal.[19]
Moringa
peregrinaleaves
70%
ethano
lextract
200mg/kg
b.w.p
.o.,on
eho
urpriorto
acetam
inop
hen,
for4weeks
Femalealbino
rats,about
160g
Acetaminop
hen-indu
cedhepatotoxicity
750mg/kg
b.w.,p.o.
Serum:A
LT,A
ST,A
LP,G
GT↑
Blood
:GSH
,CAT,SOD↓,MDA↑
Liver:GSH
,CAT,SOD
↓,GPx,MDA↑
Brain:G
SH,SOD↓,GPxandMDA↑
Serum:A
LT,A
LP(++),AST
,GGT(+++)
Blood
:GSH
,CAT,SOD,M
DA(+++)
Liver:GSH
,CAT,SOD,G
Px,MDA(+++)
Brain:G
Px,MDA(++),GSH
,SOD(+++)
Not
stud
ied
Mishra
etal.[97]
Pand
anus
odoratissimus
root
ethano
licextract
200or
400mg/kg
b.w.,p.o.,onceadayfor7
days
Wistarrats180-200g
Paracetam
ol-ind
uced
hepatotoxicity
2g/kg
b.w.,p.o.,onthe5thday
Serum:A
ST,A
LT,A
LP,d
irectbilirub
in,total
bilirub
in,T
G↑
Serum:A
LT,A
ST,A
LP,d
irectbilirub
in,
totalb
ilirubin,
TG(++);
The
protective
effectwas
better
for
thehigher
dose.
Not
stud
ied
Rashid
etal.[40]
FagoniaolivieriDC.aerialp
arts
95%
methano
licextract
200and400mg/kg,i.g.,for7days
MaleSprague-Daw
leyrats,
6-week-old,
180-200g
Acetaminop
hen-indu
cedtoxicity
750mg/kg
for7days,i.g.
Serum:A
ST,A
LT,A
LP,L
DH,totalbilirub
in,
cholesterol,TG,H
DL,
LDL↑
Blood
:HGB,W
BC↓,PLT
↑Liver:weight,CAT,SOD,G
Px,GR,G
SHand
TP↓,DNAfragmentation
andTBARS↑
Serum:A
ST,A
LT,L
DH,L
DL(++)both
doses,
ALP
,totalbilirub
in,T
G,H
DL(++200,+++400),
cholesterol(+++200,400↓)
Blood
:HGB(++both
doses),W
BC(+++both
doses),
PLT
(+++200,↑400)
Liver:TP(0
200,++400),
DNAfragmentation
,SOD,G
R,G
SH,T
BARS(++both
doses),w
eight,CAT,
GPx(++200,+++400)
400mg/kg
stud
iedon
lySerum:T
G,
HDL,
cholesterol↓
Blood
:WBC↑,
HGB↓
Liver:TBARS↓
19Oxidative Medicine and Cellular Longevity
Table6:Con
tinu
ed.
Reference
Plant
preparation,
dose,w
ayandtimeof
treatm
ent,andanim
als
The
nameof
drug,d
ose,way
andtimeof
expo
sure,and
negative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plant
perse
Ebada
[95]
Chamom
illarecutita
L.(chamom
ile)and
Cum
inum
cyminum
L.(green
cumin)
essentialo
ils(H
ashem
BrothersforEssentialOils
and
Aromaticprod
ucts)
Pretreatm
entp.o.,for
14days,
400mg/kg/day
(cum
in),250mg/kg/day
(chamom
ile)
MaleWistarrats,180-200
g
Acetaminop
hen-indu
cedhepatotoxicity
1g/kg
p.o.,a
singledo
seon
the14
thday
Serum:A
LTandAST
↑Liver:GSH
↓,MDAandSO
D↑
Liverhistop
atho
logy:h
epatocytenecrosis,
inflam
mation,
degeneration
,dilated
centralvein,
hemorrhage↑
Cum
inessentialo
il:Serum:A
LTandAST
(+++)
Liver:GSH
(0),MDA(-)andSO
D(0)
Liverhistop
atho
logy:hepatocytenecrosis,infl
ammation,
degeneration
,dilated
centralvein,
hemorrhage(++)
Chamom
ileessentialo
il:Serum:A
LT(++)andAST
(0)
Liver:MDA(-),GSH
,SOD(++)
Liverhistop
atho
logy:h
epatocytenecrosis,h
emorrhage
inflam
mation,
dilatedcentralvein,
degeneration
(+)
Not
stud
ied
Baalietal.[20]
Rich-po
lyph
enol
(n-butanol)fraction
sof
80%
methano
licextractof
Genista
quadriflora
Mun
byand70%
methano
licextractof
Teucrium
poliu
mgeyriiMaire
Pretreatm
ent
300mg/kg
daily,p
.o.,for10
days
MaleWistarrats,about
142g
Acetaminop
hen-indu
cedhepatotoxicity
Asingledo
seof
1g/kg,p
.o.
Plasm
a:AST
,ALT
↑Liver:SO
D,G
Px,GR,G
SH,G
ST↓,CYP2E
1,TBARSandmRNAof
TNF-αexpression
↑Livermitocho
ndria:CSandrespiratorychain
complexes
IandII↓
Genista
quadriflora
Plasm
a:AST
,ALT
(+++)
Liver:SO
D,G
Px,GSH
,GST
,TBARS,CYP2E
1and
mRNAof
TNF-αexpression
(+++),GR↑
Livermitocho
ndria:CSandrespiratory
chaincomplex
I(+++),respiratory
chaincomplex
II↑
Teucrium
poliu
mgeyrii
Plasm
a:AST
,ALT
(+++)
Liver:SO
D,G
Px,GSH
,GST
,TBARS,CYP2E
1and
mRNAof
TNF-αexpression
(+++),GR↑
Livermitocho
ndria:CS(+++),respiratory
chaincomplexes
IandII↑
Not
stud
ied
UthayaKum
aretal.[96]
Cassiasurattensisseed
methano
lextract
Pretreatm
ent250or
500mg/kg
b.w.,p.o.,
once
daily
for7days
MaleSw
issalbino
mice,6-8-week-old,
25-
30g
Paracetam
ol-ind
uced
hepatotoxicity
Asingledo
seof
1g/kg
b.w.,p.o.
Relativeliver
weight:↑
Serum:A
LT,A
ST,A
LP↑
Liver:GSH
,SOD↓,MDA↑
Relativeliver
weight:(+++both
doses)
Serum:A
LT,A
ST,A
LP(++both
doses)
Liver:MDAandGSH
(++250,+++500),
SOD(++250,↑500)
Not
stud
ied
Chinn
appan
etal.[22]
Eurycomalongifo
liaroot
water
extract
Physta®
(Biotrop
icsMalaysia)
100,200or
400mg/kg,p
.o.,1ho
urbefore
paracetamol,
for14
days
MaleWistarrats,12-week-old,
120-150g
Paracetam
ol-ind
uced
neph
rotoxicity
200mg/kg
daily
for14
days,i.p.
Serum:T
P,A
LB↓,creatinine
↑Blood
:urea↑
Creatinineclearance:↓
100mg/kg:
Serum:A
LB,creatinine(0),TP(+)
Blood
:ureaand(0)
Creatinineclearance:(0)
200and400mg/kg:
Serum:T
P,A
LB,creatinine(+++)
Blood
:urea(+++)
Creatinineclearance:(+++)
Not
stud
ied
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(+):aslight
beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no
beneficialeffect;(-):intensification
oftheharm
fuleffect.
20 Oxidative Medicine and Cellular Longevity
Table7:The
protective
prop
erties
ofplantextractsagainstside
effectsof
antibiotics.
Reference
Plant
preparation,
dose,treatment
way
andtime,andanim
als
The
nameofdrug,dose,expo
sureway
andtime,andnegative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plantperse
Valipou
retal.[98]
Ferulago
angulata
Ethanol:w
ater
(70:30,v/v)
extract
200,400,or
800mg/kg
b.w.,
p.o.,for
7days
MaleWistarrats,about
200g
Gentamicin
120mg/kg
b.w.,daily
for
7consecutivedays,i.p.
Serum:H
DL↓;TG,T
C,L
DL,
UA,
urea,C
R,P
C,T
NF-α,M
DA↑
Kidney:CAT,SODandAA↓,MDA
andrelative
expression
ofTNF-α↑
Serum:H
DL(0
200and400,+++800),C
R(+
200,++400and800),P
C(+
200,++400,+++800),
UAandurea
(++alld
oses),TC,L
DL,
TNF-αand
MDA(++200and400,+++800),T
G(++200,+++400and800)
Kidney:SO
D(0
200,++400and800),relative
expression
ofTNF-α(0
200,++400,+++800),
AA(0
200,+++400and800),C
AT(++200and
400,+++800),M
DA(++200,+++400and800)
Not
stud
ied
Borou
shaki
etal.[29]
Rheum
turkestanicum
root
70%
ethano
lextract
100or
200mg/kg,for
6days,i.p.,1
hour
before
gentam
ycin
MaleWistarrats,250-300
g
Gentamycin
80mg/kg/day,
for6days,i.p.
Serum:C
Randurea
↑Kidney:MDA↑,totalSH
content↓
Urine:p
rotein
andglucose↑
Serum:C
R,u
rea(++both
doses)
Kidney:MDA,totalSH
content(++both
doses)
Urine:p
rotein
(0100,++200),
glucose(+
100,++200)
Not
stud
ied
Apaydin
Yild
irim
etal.[28]
Helichrysum
plicatum
DC.sub
sp.
plicatum
aerialpartsethano
lextract
100or
200mg/(kg·d
)i.p.,for8days
MaleSprague-Daw
leyrats
Gentamicin
80mg/(kg·d
)i.p.,for8days
Serum:B
UN
andcreatinine
↑Liver:CATandSO
D↓;MDA,
degeneration
,necrosis,inflam
matory
cells, biliaryhyperplasia↑
Kidney:SO
D,C
AT,G
Px↓,MDA,
inflam
matorycells,d
egeneration,
necrosis↑
Serum:B
UN
andcreatinine
(++both
doses)
Liver:SO
D(++100,0200),M
DA(++100,+++200),
CAT(+++100,++200),n
ecrosis,degeneration
(++
100,+200),infl
ammatorycells
(+++100,+200),
biliary
hyperplasia(++both
doses)
Kidney:GPx(bothdo
ses),SOD(+++100,0200),
MDA,C
AT(+++100,++200)
Kidney:degeneration
andinflam
matorycells
(++100,+200),n
ecrosis(++both
doses)
Serum:B
UN
(↓100,↑200)
Liver:CAT(↓
200),infl
ammatory
cells,biliaryhyperplasiaandnecrosis
(↑200),d
egeneration
(↑both)
Kidney:CAT(↑
both
doses),
inflam
matorycells
andnecrosis
(↑200),d
egeneration
(↑both)
Zhang
etal.
[99]
Pana
xnotoginsengsapo
nins
(GuangxiWuzho
uPharm
aceutical
Co.,L
td.H
angzho
u,China)
10mg/kg,twiceadayfor
14days,i.m
.FemaleICRmice,18-20g
Polym
yxin-ind
uced
neph
rotoxicity
15mg/kg
twiceadayfor14
days,i.m
.Kidneyweight:body
weightratio:↑
Serum:B
UN,C
R↑
Kidney:SO
D↓,MDAandnu
mberof
apop
toticcells
↑
Kidneyweight:body
weightratio:(++)
Serum:B
UN,C
R(+++)
Kidney:nu
mberof
apop
toticcells
(++),
SODandMDA(+++)
Non
e
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(+):aslight
beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no
beneficialeffect;(-):intensification
oftheharm
fuleffect.
21Oxidative Medicine and Cellular Longevity
Table8:The
protective
effectsof
plantpreparations
againstside
effectsof
anticancer
agents.
Reference
Plant
preparation,
dose,treatmentway
andtime,andanim
als
The
nameof
drug,d
ose,expo
sure
way
andtime,andnegative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plantperse
Kim
etal.[100]
Dendropan
axmorbifera
The
CHCl 3fraction
of70%
methano
l
leafextract
25mg/kg
once
at24
hbefore
cisplatin
andon
ceadayfor5days
after,i.p.
SpragueDaw
leymalerats,
8weeks,about
200g
Cisplatin,a
singleadministrationof
6mg/kg,i.p.
Bod
yweight:↓
Kidney/body
weightratio:↑
Serum:B
UN,C
R↑
Kidney:SO
D↓,cleavedcaspase-3
andacutetubu
larnecrosisscore↑
Bod
yweight:(++)
Kidney/body
weightratio:(+++)
Serum:C
R(++),BUN
(+++)
Kidney:acutetubu
larnecrosisscore
(++),SO
Dandcleaved
caspase-3(+++)
Not
stud
ied
Kpemissi
etal.[102]
Com
bretum
micranthu
mleaf
ethano
l-water
(8:2)extract
200or
400mg/kg/day
p.o.,for
10days
MaleWistarrats,
6-8-week-aged,200-250
g
Cisplatin
7.5mg/kg,i.p.,
asingleinjectionon
the5thday
Bod
yweight:↓
Relativekidn
eyweight:↑
Serum:C
R,u
rea,UA,A
LT,A
ST,
GGT,A
LP↑,TP,A
LB,C
a,
Mg,P,N
O,F
RAP↓
Urine:C
R,u
rea,UA,P
↓,TP,A
LB,C
a,Mg,↑
Kidney:MDA↑,FR
AP,
NO,G
SH↓
Bod
yweight(++both
doses)
Relativekidn
eyweight:
(+++200,++400)
Serum:urea(+++200,++400),C
R,U
ATP,A
LB,
Ca,Mg,P,A
LT,A
ST,A
LP,N
O,F
RAP
(+++both
doses),G
GT(↓
both
doses)
Urine:C
R,u
rea,UATP,
(+++200,++400),A
LB,
Ca,Mg,P(+++both
doses)
Kidney:NO,G
SH(++both
doses),F
RAP
(+++200,++400),
MDA(+++both
doses)
Not
stud
ied
Hosseinian
etal.[16]
Nigellasativa
seeds70%
ethano
lextract
100or
200mg/kg,i.p.
(i)Pretreatm
ent(6
days)+salin
efor
5days
aftercisplatin
(ii)Pretreatm
ent(6
days)+extractfor
5days
aftercisplatin
MaleWistarrats,230-300
g
Cisplatin
6mg/kg
onthe6thdayof
theexperiment,i.p.
Serum:totalSH
↓,MDA↑
Kidney:totalSH
↓,MDA↑slightly
Renaltissue
damage:↑
(i)Serum:M
DA(+++both
doses),
totalSH
(+++100,↑200)
Kidney:MDA(-both
doses),
totalSH
(+++both)
Renaltissue
damage:(++both
doses)
(ii)Serum:M
DA(+++both
doses),
totalSH
(↑both)
Kidney:MDA(-100,+++200),
totalSH
(+++both)
Renaltissue
damage:(++both
doses)
Not
stud
ied
Chenetal.[25]
Totalflavon
oids
from
Clin
opodium
chinense(Benth.)
Pretreatm
ent
20,40,or
80mg/kg,i.g.,for15
days
MaleSprague-Daw
leyrats,220-250
g
Doxorub
icin-ind
uced
cardiotoxicity
3mg/kg,i.p.,everytwodays
fora
totalo
fthreeinjections
Bod
yandheartweight:↓
Serum:A
ST,L
DH,C
K↑
Heart:SOD,C
AT,G
Px↓,MDA↑
Bod
yandheartweight:
(++20,+
++40
and80)
Serum:C
K,L
DH
(++20,+
++40
and
80),AST
(+++alld
oses)
Heart:G
Px(+
20,+
+40
and80),CAT
(++alld
oses),MDA,SOD
(++20,+
++40
and80)
80mg/kg
only
stud
ied:
none
22 Oxidative Medicine and Cellular Longevity
Table8:Con
tinu
ed.
Reference
Plant
preparation,
dose,treatmentway
andtime,andanim
als
The
nameof
drug,d
ose,expo
sure
way
andtime,andnegative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plantperse
Ahm
edetal.[24]
Allium
sativum
(garlic)aqueou
sextract
1mL/100gb.w.,p.o.,d
ailyfor7days
before
and7days
aftermetho
trexate
MaleWistarrats,100–120
g
Metho
trexate-indu
ced
neph
rotoxicity
20mg/kg,a
singleinjection,
i.p.
Serum:u
rea,CR,K
,P↑,Na↓
Kidney:GSH
,CAT↓,MDA,
ADA,N
O↑
Serum:u
rea(↓),P(+),
CR,K
,Na(+++)
Kidney:MDA,N
O(++),GSH
,CAT,A
DA(+++)
Non
e
Tag
etal.[37]
Morus
nigra(m
ulberry)
leaves
50%
ethano
lextract
500mg/kg,i.g.,daily
for14
days
Malealbino
rats,180–200
g
Metho
trexate-indu
ced
hepatotoxicity,a
singledo
se,
20mg/kg,on4thday,i.p.
Liverweight/body
weight:↑
Serum:A
ST,A
LT,A
LP,L
DH
↑Liver:totalp
atho
logicalscore
↑,meanscoreof
hepatocyte
degeneration
,con
gestion,
cellu
lar
infiltration,
fibrosis↑
Liverweight/body
weight:(++)
Serum:A
LP(++),AST
,ALT
,LDH
↓Liver:totalp
atho
logicalscore
(++),
meanscoreof
hepatocytedegeneration
,congestion
,cellularinfiltration
and
fibrosis(++)
Serum:A
ST,A
LT,
ALP
,LDH
↓
Moghadam
etal.[103]
CurcumalongaL.,ethanol
extract
100or
200mg/kg,p
.o.,for30
days
MaleWistarrats,220–280
g
Metho
trexate-indu
ced
hepatotoxicity,a
singledo
se
20mg/kg
i.p.,on
day30
th
Bod
yweight:
Liverweight:↑
Serum:A
LB,T
P↓,ALT
,AST
,ALP
,
bilirub
in↑
Plasm
a:TAS↓
Liver:SO
D,G
Px,CAT↓,MDA,
numberof
neutroph
ils,d
egree
ofinjury
↑
Bod
yweight:
Liverweightratio:(++both
doses)
Serum:A
ST,A
LP(++both
doses),
ALB
,ALT
,bilirubin,
TP
(++100,+++200)
Plasm
a:TAS(++100,+++200)
Liver:MDA,n
umberof
neutroph
ils(+
100,++200),d
egreeof
injury
(++both
doses),
SOD,C
AT,G
Px(++100,+++200)
The
higher
dose:
Liver:CAT↑
Plasm
a:TAS↑
Omole
etal.[26]
Kolaviron
—amixture
offlavon
oids
obtained
from
Garciniakolaseeds
Pretreatm
ent
200or
400mg/kg/d,p
.o.,for14
days
MaleWistarrats,120-150
g
Cycloph
osph
amide50
mg/kg/d,
i.p.,24
hoursafterthelastdo
seof
kolaviron,
for3days
Relativeheartweight:↑
Heart:SOD,C
AT,G
Px,GSH
↓,LD
H,C
K,M
DA,H
2O2,
MPO
andcT
nI↑
Relativeheartweight:
(+++200,++400)
Heart:LDH,C
K,cTnI,MPO,and
GSH
(++both
doses),G
Px,CAT,M
DA,
H2O
2(+++200,++400),
SOD
(+++)both
doses
Non
e
23Oxidative Medicine and Cellular Longevity
Table8:Con
tinu
ed.
Reference
Plant
preparation,
dose,treatmentway
andtime,andanim
als
The
nameof
drug,d
ose,expo
sure
way
andtime,andnegative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plantperse
Shew
eita
etal.[101]
Essentialoilsof
Foeniculum
vulgareMiller
(fennel)seeds,
Cum
inum
cyminum
L.(cum
in)seeds,andSyzygium
arom
aticum
L.(clove)flow
erbu
ds(0.12mL/kg
b.w.,
0.10
mL/kg
b.w.,and0.106mL/kg
b.w.,(1/50LD
50do
ses),
respectively),p.o.for28
days
MaleSw
issalbino
mice,abou
t25
g
Cycloph
osph
amide
2.5mg/kg
b.w.for
28days,p
.o.
Serum:A
LT,A
ST,A
LP↑
Liver(S9fraction
):TBARS↑;GSH
,GPx,GR,G
ST,SOD,C
AT↓
Hepaticmicrosomalfraction
:NADPH-cytochrom
ec
redu
ctase↑
Serum:A
LT,A
ST,A
LP(++allo
ils)
Liver(S9fraction
):TBARS(++clove
oil,+++fenn
elandcumin
oils);GPx,
GSH
,GR,SOD,C
AT(+++allo
ils);
GST
↑allo
ilsHepaticmicrosomalfraction
:NADPH-
cytochromecredu
ctase
(0allo
ils)
Liver:TBARS↓,
GPx,CAT,G
ST↑(alloils),GR↑
(cum
inandclove),G
SH,SOD
↑(cum
in),NADPH-cytochrom
ec
redu
ctase↑(all)
Rahateand
Rajasekaran
[27]
Desmostachya
bipinn
ataStapf(L.)
roots—
thepo
lyph
enolicfraction
of70%
methano
lextract
100or
200mg/kg
b.w.,p.o.,21days
Sprague-Daw
leyfemalerats,150–200
g
Tam
oxifencitrate
45mg/kg
b.w.,p.o.,10th–21s
tdays
Serum:p
rotein
↓,AST
,ALT
,ALP
,
cholesterol,TG,u
rea,CR,
UA,bilirubin↑
Liver:LP
O↑,GSH
,GPx,
SOD,C
AT↓
Serum:p
rotein,A
ST,A
LT,cho
lesterol,
TG,u
rea,UA(++both
doses),C
R,
bilirub
in(++100,+++200),
ALP
(++100,↓200)
Liver:CAT(+
100,++200),LPO,G
SH,
GPx,SO
D,(++both
doses)
Not
stud
ied
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(+):aslight
beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no
beneficialeffect;(-):intensification
oftheharm
fuleffect.
24 Oxidative Medicine and Cellular Longevity
Table9:The
protective
effectsof
plantpreparations
againstside
effectsof
variou
sdrugs.
Reference
Plant
preparation,do
se,treatmentw
ayandtime,
anim
als
The
nameof
drug,d
ose,expo
sure
way
andtime,
negative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plant
perse
Ben
Saad
etal.[104]
Opu
ntiaficus-indica
cladod
eextracto
btainedby
homogenizationwith10
mM
TrisHCl,pH
7.4,
andsubsequent
centrifugation
Pretreatm
ent,100mg/kg
b.w.
30-day
pretreatmentandthen
for30
days
together
withlithium
MaleWistarrats,2
mon
ths
Li(lithium
carbon
ate),25mg/kg
b.w.,i.p.,
twicedaily
for30
days
Serum:glucose,T
C,T
G,A
LT,A
ST,
LDH,A
LP↑
Blood
:RBC,H
GB,H
CT↓,WBC↑
Liver:SO
D,C
AT,G
Px↓,MDA↑
Serum:A
LT,A
ST(++),glucose,TC,T
G,
ALP
,LDH
(+++)
Blood
:RBC,H
GB,H
CT,W
BC(++)
Liver:CAT(++),SO
D,G
Px,MDA(+++)
Non
e
Khalil
etal.[105]
Withaniasomnifera
leaf
70%
ethano
lextract
Pretreatm
ent,100mg/kg
b.w.,
for4weeks
MaleWistarrats,140–160
g
Isop
rotereno
l85mg/kg
b.w.,s.c.on
29thand30
th
days
Serum:T
C,T
G,V
LDL-c,cT
nI,C
K-M
B,
LDH,A
ST,A
LT↑,HDL-c↓
Heart:SOD,G
R,G
Px,GST
↓,MDA,w
eight↑
Serum:C
K-M
B(0),TC,T
G,V
LDL-c,
cTnI,L
DH
(++),HDL-c,AST
,ALT
(+++)
Heart:SOD,w
eight(++),GR,G
Px,
GST
,MDA(+++)
Serum:
HDL-c↑
Heart:G
Px,
GST
↑
Dianita
etal.[106]
Labisiapu
mila
var.alatawater
and80%
ethano
licextracts
100,200,or
400mg/kg,p
.o.,for28
days
MaleWistarrats,150-200
g
Isop
rotereno
l,85
mg/kg
ofs.c.,on29
thand30
th
dayof
theexperiment
Serum:cTnI,C
K-M
B,L
DH,A
ST,A
LT↑,
SOD,C
AT,G
Px↓
Heart:SOD,C
AT,G
Px↓
Serum:cTnI
(water
extract++alld
oses,
ethano
lextract++100and200,+++400),
CK-M
B,L
DH,A
ST,A
LT,SOD,C
AT,
GPx(++both
extractsalld
oses)
Heart:SOD,G
Px(w
ater
extract+100,++200
and400,ethano
lextract++alld
oses),
CAT(++both
extracts,alldo
ses)
Not
stud
ied
Shahat
etal.[107]
Rhu
stripartita80%methano
lextractof
thestem
partof
malegeno
type
250or
500mg/kg/day
p.o.,for
21days
(19-day-pretreatment)
MaleWistarrats,about
180g
Isop
rotereno
l85mg/kg,s.c.on20
thand21
stdays
Serum:A
ST,A
LT,G
GT,A
LP,L
DH,C
K,T
C,
TG,L
DL-c,VLD
L-c↑,H
DL-c↓
Heart:M
DA↑,NP-SH
andTP↓
Serum:L
DH,H
DL-c(+
250,++500),A
ST,
ALT
,GGT,A
LP,C
K,T
C,T
G,L
DL-c
andVLD
L-c(++both
doses)
Heart:M
DA,N
P-SH
andTP
(++both
doses)
Not
stud
ied
Kem
kaNguim
atio
etal.[108]
Afram
omum
melegueta
seed
water
and
methano
lextracts
20or
100mg/kg
for28
days
MaleWistarrats,sexually
experienced,
3-mon
th-old,200-250
g
Propylth
iouracil-indu
cedhypo
thyroidism
causingejaculatorycomplications
10mg/[kg·d
ay]for28
days
Plasm
a:T↓,TSH
andprolactin↑
Proejaculatoryactivity
(con
tractileactivity
ofthestriated
bulbospo
ngiosusmuscles):nu
mber
ofcontractions
aftertactile
stim
ulationand
pharmacologicalactivation
(dop
amine)
↓,intrasem
inalpressure
aftertactile
stim
ulationand
pharmacologicalactivation
(dop
amine)
↓
Water
extract:
Plasm
a:TSH
(0both
doses),T
(+20,+
++100),
prolactin(+
20,+
+100)
Proejaculatoryactivity:con
traction
snu
mber
afterboth
stim
uli(+++20,↑
100),intraseminal
pressure:tactilestim
ulation(↑
both
doses),
pharmacologicalactivation
(+++both
doses)
Methano
lextract:
Plasm
a:TSH
(020,+
100),T
(+20,+
+100),
prolactin(++20,+
100)
Proejaculatoryactivity:con
traction
snu
mber
afterboth
stim
uli(↑both
doses),intraseminal
pressure:tactilestim
ulation(↑
both
doses),
pharmacologicalactivation
(+++20,↑100)
Not
stud
ied
25Oxidative Medicine and Cellular Longevity
Table9:Con
tinu
ed.
Reference
Plant
preparation,do
se,treatmentw
ayandtime,
anim
als
The
nameof
drug,d
ose,expo
sure
way
andtime,
negative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plant
perse
Nasrietal.
[109]
Green
tea70%
ethano
lextract
Posttreatment:afteriodixano
l,10
mg/kg/d,i.p.,for3days
Pretreatm
ent10
mg/kg/d,i.p.,for3
days
andiodixano
lonthe3r
dday
MaleWistarrats,6-w
eek-aged,200-250
g
Iodixano
l,acontrastmedium
10mL/kg,i.v.,asingledo
seRenaltubu
larcells:d
ilatation
,degeneration
,vacuo
lization,
debris↑
Posttreatment:
Renaltubu
larcells:d
ilatation
,degeneration
,vacuo
lization,
debris(++)
Pretreatm
ent:
Renaltubu
larcells:d
ilatation
,degeneration
,vacuo
lization,
debris(++)
Pretreatm
entshow
edaslightlybetter
effect
Not
stud
ied
El-Rahman
etal.[110]
Saussurealapparoots
70%
ethano
lextract
600mg/kg,p
.o.,daily
Cotreatmentfor2weeks
concurrently
withthedrug
Pretreatm
entfor1weekandthen
for2weeks
concurrentlywiththedrug
Malealbino
rats,150–160
g
Triam
cino
lone
aceton
ide
40mg/kg,i.p.,twiceaweekfor2weeks
Serum:T
NF-α,C
RP,IL-12,IgG
,IgM
↓Lu
ng:G
Px,SO
D↓,MDA↑
Spleen:G
Px,SO
D↓,MDA↑
Histopathologicallesion
score:spleen
andlung
↑
Cotreatment:
Serum:T
NF-αandCRP(0),IL-12and
IgG(+),IgM
(++)
Lung:G
Px(+),SO
D,M
DA(++)
Spleen:G
Px,SO
D,M
DA(++)
Histopathologicallesion
:spleen
andlung
(++)
Pretreatm
ent:
Serum:T
NF-α,IL-12,C
RP(0),IgG,IgM
(++)
Lung:G
Px,SO
D,M
DA(++)
Spleen:G
Px,SO
D(++),MDA(+++)
Histopathologicallesion
:spleenandlung
(++)
Serum:T
NF-α,
CRP,IL-12,↓,
IgG,IgM
↑Lu
ng:G
Px,
SOD↑,MDA↓
Spleen:G
Px,
SOD↑,MDA↓
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(+):aslight
beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no
beneficialeffect.
26 Oxidative Medicine and Cellular Longevity
Table10:T
heprotective
effectsof
plantorigin
materialsin
theanim
almod
elof
arthritis.
Reference
Plant
extract,do
se,w
ayandtimeof
treatm
ent,
andanim
als
Indu
cing
factor
andnegative
effects
Protectiveeffectsof
plantmaterial
Effectsof
plant
perse
Cho
udhary
etal.[49]
Spinacia
oleracea
leaf
ethano
lextract
250or
500mg/kg/day,for
28days,p
.o.
Health
yandpathogen-freefemaleSprague-
Daw
leyrats,4–16weeks,180-200
g
Osteoarthritis,indu
cedby
mon
osod
ium
iodo
acetate,asingleinjectionof
3mgthroughthe
intra-articularjointof
theleftkn
eeSerum:G
ST,C
OMP↑
Urine:C
TX-II↑
Isolated
bone
region
containing
cartilage
andsub-
chon
dralbone:relativemRNAexpression
ofIL-1β,
TNF-α,C
OL1
0,MMP-1,M
MP-3,M
MP-13↑,
relative
mRNAexpression
ofBMP2,COL2
,AGGRECAN,T
IMP1,TIM
P2↓
Serum:C
OMP(+
250,++500),G
ST(++both
doses)
Urine:C
TX-II(+
250,++500)
Isolated
bone
region
containing
cartilage
andsub-chon
dralbone:relativemRNA
expression
ofTNF-αandMMP-13
(+250,++500);relativemRNAexpression
ofIL-
1β,C
OL1
0,MMP-1,M
MP-3
(++both
doses);
relative
mRNAexpression
ofBMP2,COL2
and
TIM
P1(0
250,++500),relativemRNAexpression
ofTIM
P2andAGGRECAN
(++both
doses)
Not
stud
ied
Jeon
getal.
[48]
Morus
alba
L.leafwater
extract
100mg/kg,p
.o.,on
ceperdayfor3weeks
MaleSpragueDaw
leyrats,180-240
g,5-week-old
Osteoarthritis,indu
cedby
mon
osod
ium
iodo
acetate,asingleinjection3mg/kg
into
therightkn
eejoint
Serum:IL-1β
,IL-6,TNF-α,INF-γ,
NO,P
GE2,COMP,C
TX-II↑
Articular
cartilage:expressionof
MMP-13↑
Serum:INF-γ(0),IL-1β,IL-6,TNF-α,
NO,P
GE2,
CTX-II,COMP(++)
Articular
cartilage:expressionof
MMP-13(++)
Articular
cartilage:a
slight
increase
inMMP-13
expression
Sund
aram
etal.[55]
Guggulip
id,anethylacetateextractrich
inlip
idsfrom
Com
miphora
whighitiigum
resin,
obtained
byextraction
ofgugguluoleoresin
(NKCAph
armacy,Musurum
India)
50or
100mg/kg/day,for
15days,p
.o.
Adu
ltWistarrats,10-week-old
Experim
entalarthritisindu
cedby
100μLof
FCA
(Freun
d’scompleteadjuvant
containing
10mg/mL
heat-killed
Mycobacterium
tuberculosis)injected
attheback
surfaceof
righthind
paw,s.c.
Blood
:WBC↑,RBC,H
GB,P
LT↓
Serum:expressionof
MMP-1,M
MP-3,
MMP-9,M
MP-13↑
Serum:A
LTAST
,SOD,C
ATandGST
↑Liverandspleen:R
OS,hydrop
eroxides,L
PO,P
C,
NO2- ,
GSSG,SOD,C
AT,G
ST↑,GSH
,GPx,GR↓
Ank
lejointho
mogenate:ACP,A
LP↑
Blood
:HGB(0
50,+
+100),W
BC,R
BC
(++bo
thdo
ses),P
LT(++50,+
++100)
Serum:M
MP-1
(+50,+
++100),M
MP-3
(+50,+
+100),M
MP-9
(++50,+
++100),
MMP-13(+++both
doses)
Serum:A
LT,A
ST,C
AT(++50,+
++100),
SOD
andGST
(+++both
doses)
Liver:ROS,hydrop
eroxides,G
Px,CAT(++both
doses),L
PO,P
C,N
O2- ,
SOD,G
SH,
GSSGandGR(++50,+
++100)
Spleen:R
OS,hydrop
eroxides
(++both
doses),
LPO,P
C,N
O2- ,
GR,G
SH,G
SSG(++50,+
++100),
SOD,C
AT,G
ST(+++both
doses)
Ank
lejointho
mogenate:ACP(+
50,+
+100),
ALP
(++both
doses)
Not
stud
ied
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(+):aslight
beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no
beneficialeffect.
27Oxidative Medicine and Cellular Longevity
Table11:T
heprotective
effectsof
plantorigin
materialsin
theanim
almod
elof
neurod
egenerativedisorders.
Reference
Plant
extract,do
se,w
ayandtimeof
treatm
ent,
andanim
als
Disorder,indu
cing
factor,and
negative
effects
Protectiveeffectsof
plantmaterial
Effects
ofplant
perse
Hritcuetal.[32]
Pipernigrum
fruitsmethano
licextract50
or100mg/kg,p
.o.,daily,for
21days
MaleWistarrats,3
mon
th-old,about
250g
Animalmod
elof
Alzheim
er’sdisease
400pm
olAβ(1–42),i.c.v.,20
days
prior
tomethano
licextract
Amygdala:G
Px,GSH
↓,CAT,P
C,M
DA↑
The
lower
dose:
Bilateralamygdala:G
Px↑,GSH
(0),
PCandCAT↓,MDA(+++)
The
higher
dose:M
DA,P
C,C
AT↓,
GSH
(++),GPx(+++)
Not
stud
ied
Malik
etal.[39]
Celastrus
paniculatusseed
ethano
lextract
Pretreatm
entfor6days
100or
200mg/kg,
p.o.,and
then
treatm
entconcom
itantly
with3-nitrop
ropion
icacid
MaleWistarrats,220–250
g
3-Nitroprop
ionicacid-ind
uced
Hun
tington’sdiseasesymptom
s,10
mg/kg,i.p.,for14
days
Bod
yweight↓
Striatum
:MDA,N
O2-↑,CAT,SOD,G
SH↓
Cortex:MDA,N
O2-↑,CAT,SOD,G
SH↓
Bod
yweight:(++both
doses)
Striatum
:MDA,N
O2- ,
CAT,SOD,
GSH
(++both
doses)
Cortex:MDA,N
O2- ,
CAT,SOD,
GSH
(++both
doses)
Not
stud
ied
Cho
npatho
mpiku
nlert
etal.[31]
Apium
graveolens
L.,70%
methano
licextract
125,250,and375mg/kg
b.w.,p.o.,for
21days
MaleC57BL/6mice,2mon
ths,25–30g
Parkinson
’sdiseaseindu
cedby
1-methyl-4-
phenyl-1,2,3,6-tetrahydrop
yridine,15
mg/kg
perday,i.p.,dividedinto
4injections
at2h
intervalson
asingleday
Cortex:MDA,M
AO-A
,MAO-B
↑,GPx↓
Striatum
:MDA,M
AO-A
,MAO-B
↑,GPx↓
The
lowestdo
se:
Cortexandstriatum
:MAO-A
,GPx(0),MDA,
MAO-B
(++)
The
middledo
se:
Cortex:MAO-B
MAO-A
,GPx(++),
MDA(+++)
Striatum
:MAO-B
MAO-A
,GPx
andMDA(++)
The
highestdo
se:
Cortex:MDA,M
AO-B,M
AO-A
andGPx(+++)
Striatum
:MDA↓,MAO-B,M
AO-A
,GPx(+++)
Not
stud
ied
Wangetal.[38]
Rhizomadrynariae(a
commercialprod
uct)
madefrom
driedrootsof
Dryna
riafortun
eiwater
extract
20mg/kg
p.o.,d
aily,for
14or
28days
MaleSprague-Daw
leyrats,about
250g
Con
trolledcorticalim
pact(CCI)mod
elof
traumaticbraininjury
Plasm
a:IL-6
after1,3,7,14,21,and28
days
↑Brain:m
icroglialactivationafter1,3,7,
and14
days
↑
Plasm
a:IL-6
(0after3and7days,++after1day,
+++after14,21,and28
days)
Brain:m
icroglialactivation(0
after1day,
++after3,7,and14
days)
Not
stud
ied
Xuetal.[60]
Rhu
barb
(three
speciesareassigned
asoffi
cial
Rhu
barb,i.e.,Rheum
palm
atum
L.,R
heum
tanguticum
Maxim
.exBalf.,
andRheum
officina
leBaill),a
commercialprod
uct,water
extract
3,6,12
g/kg
ofRhu
barb
p.o.,after
trauma
MaleSprague-Daw
leyrats,200-300
gsacrificed
8,16,or24
hoursafterRhu
barb
Con
trolledcorticalim
pact(CCI)mod
elof
traumaticbraininjury
Brain
8hafterRhu
barb:M
DA↑,SO
D,
CAT,G
SH/G
SSG↓
Brain
16hafterRhu
barb:M
DA↑,SO
D,
CAT,G
SH/G
SSG↓
Brain
24hafterRhu
barb:M
DA↑,SO
D,
CAT,G
SH/G
SSG↓
Brain
8hafterRhu
barb:M
DAand
CAT(0
3and6,++12),SO
D(0
3,+6,++12),GSH
/GSSG
(+3,++6,+++12)
Brain
16hafterRhu
barb:M
DA
(03,++6and12),SO
D(++3and6,+++12),CAT
(03,++6and12),GSH
/GSSG(0
3,+6,++12)
Brain
24hafterRhu
barb:M
DA(++3and6,++
+12),SO
D(+
3,++6,+++12),CAT(0
3,++6
and12),GSH
/GSSG(+
3,++6,+++12)
Not
stud
ied
28 Oxidative Medicine and Cellular Longevity
Table11:C
ontinu
ed.
Reference
Plant
extract,do
se,w
ayandtimeof
treatm
ent,
andanim
als
Disorder,indu
cing
factor,and
negative
effects
Protectiveeffectsof
plantmaterial
Effects
ofplant
perse
Linetal.[113]
Uncaria
hirsuta95%
ethano
land
water
extractsof
stem
swithho
oks
80mg/kg/day
p.o.for4or
8weeks
MaleBALB
/cmice,8week-old
D-G
alactose-ind
uced
neurotoxicity
(12gin
100mLof
norm
alsalin
e)0.1mLper10
gof
weight,s.c.on
ceaday,
for4or
8weeks
Plasm
a4weeks:M
DA↑
Plasm
a8weeks:M
DA↑
Brain
8weeks:M
DA↑
Ethanol
extract:
Plasm
aMDA:4
weeks
(++),
8weeks
(+++)
Brain
MDA:8
weeks:(++)
Water
extract:
Plasm
aMDA:4
weeks
(++);
8weeks
(+++)
Brain
MDA:8
weeks
(++)
Not
stud
ied
Moh
aleetal.[111]
Nerium
indicum
flow
ersethylacetateextract
200and400mg/kg,oncedaily
p.o.
MaleSprague-Daw
leyrats,200–250
g
Anx
iety
indu
cedby
21-day
isolation
indark
room
Blood
:LPO
↑,SO
D,C
AT,G
SH↓
Brain:L
PO
↑,SO
D,C
AT,G
SH↓
Blood
:GSH
(+both
doses),
SOD(++both
doses),C
AT
(++200,+++400),L
PO
(+++both
doses);
Brain:C
AT(++)both
doses,SO
DandGSH
(++200,+++400),L
PO
(+++both
doses)
Not
stud
ied
Wuetal.[112]
Malva
sylvestrisL.
leafandflow
er95%
methano
lextract
250mg/kg
perday,i.g.,for7days
Adu
ltSP
F-grademice
Lipo
polysaccharide-ind
uced
depression
250μg/kg
i.p.,adaybefore
treatm
ent(priorto
injectionsulin
dacsulfide
3.75
or7.5mg/kg
for>3
weeks)
Cortex:astroglio
sis,IL-1,IL-6,TNF-α↑,
numberof
survivalneuron
s↓
Hippo
campu
s:astroglio
sis,IL-1,IL-6,
TNF-α↑,nu
mberof
survivalneuron
s↓
Cortex:nu
mberof
survivalneuron
s,astroglio
sis,IL-1,IL-6,TNF-α(++)
Hippo
campu
s:nu
mberof
survivalneuron
s,astroglio
sis,IL-1,IL-6,TNF-α(++)
Not
stud
ied
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(+):aslight
beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no
beneficialeffect.
29Oxidative Medicine and Cellular Longevity
Table12:T
heprotective
effectsof
plantorigin
materialsin
theanim
almod
elof
menop
ause.
Reference
Plant
extract,do
se,w
ayandtimeof
treatm
ent,
andanim
als
Indu
cing
factor
andnegative
effects
Protectiveeffectsof
plantmaterial
Effectsof
plantperse
Leun
getal.[115]
Cam
ellia
sinensisO.K
tze(black
tea)
extract(Q
P-lackteaextract,
QualityPhytochem
icalsLL
C)
15mg/kg/day,i.g.,for4weeks,3
mon
ths
afterovariectom
yFemaleSprague-Daw
leyrats,
3mon
ths,200–230g
Ovariectomy
Bod
yweight:↑
Serum:17β
-estradiol,cGMP↓,no
n-HDL-c,HDL-c,TC,T
G↑
Aorta:p
eNOS↓,NOX2,NOX4↑
End
otheliu
mof
aorta:ROS↑
Bod
yweight:(0)
Serum:T
G↓,17β-estradiol,
non-HDL-c(0),HDL-c,TC
(++),cG
MP(+++)
Aorta:p
eNOS,NOX2,NOX4(+++)
End
otheliu
mof
aorta:ROS(+++)
Not
stud
ied
Galanisetal.[114]
Glycyrrhiza
glabra
root
methano
lextract,in
theform
ofdrinking
water
atsuch
avolume
soas
toobtain
theup
perthresholdof
glycyrrhizin
(the
mainactive
compo
nent)
of12.4mg/kg/rat
perday,adayaftersurgery,
for3or
6mon
ths
FemaleintactmatureWistar
rats,10mon
ths
Ovariectomy
Totaltibiabone
mineraldensity:after3
and6mon
ths↓
Proximaltibiabone
mineraldensity:
afterboth
3and6mon
ths↓
Uterine
weight:after6mon
ths↓
Totaltibiabone
mineraldensity:(+++after3
mon
ths,++after6mon
ths)
Proximaltibiabone
mineraldensity:
after3mon
ths(+++),after6mon
ths(++)
Uterine
weight:(++)
Not
stud
ied
Ham
metal.[116]
Hum
ulus
lupu
lusL.,h
opsflavon
oid-rich
extract
(MetaG
enics,AlisoViejo,C
A,U
SA)
400mg/kg
infood
,daily,for
11weeks
FemaleC57BL/6mice,7mon
ths
Ovariectomy
Uterusweight↓
Visceraladipo
setissue
weight↑
Liver:TG↑
Ileum:A
LP↑
Uterusweight(0)
Visceraladipo
setissue
weight(+)
Livertriglycerides(+++)
Ileum: A
LP(0)
Uterusweight
↓Ileum:A
LP↑
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(+):aslight
beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no
beneficialeffect.
30 Oxidative Medicine and Cellular Longevity
Table13:T
heprotective
effectsof
plantorigin
materialsin
lung
disorders.
Reference
Plant
extract,do
se,w
ayandtimeof
treatm
ent,and
anim
als
Indu
cing
factor
andnegative
effects
Protectiveeffectsof
plantmaterial
Effectsof
plantperse
Taguchi
etal.[118]
Saku
ranetin,
aflavon
oidobtained
from
methano
lextractof
aerialpo
rtions
ofBaccharisretusa
bysuccessive
extraction
andseparation
from
CH
2Cl 2
phase
Posttreatment-20mg/kg
viaintranasalinstillationon
days
0,7,14,and
28(the
endof
theexperiment)
C57BL6
malemice,7-9-week-old,
25g
Emph
ysem
aindu
cedby
elastase,50μL
(6.6un
its/mg),anintranasaldrop
(0.667
IU)
BALF
:macroph
ages,lym
phocytes,
neutroph
ils,eosinop
hils,totalcells
↑Lu
ng:N
F-κB
,M-C
SF,IL-1β
,MCP-1,T
NF-α
↑,expression
ofTIM
P-1,M
MP-9,M
MP-12↑
Lung:collagenandelasticfiberdepo
sition
↑
BALF
:eosinop
hils(-),macroph
ages,
lymph
ocytes,n
eutrop
hils,totalcells
(++)
Lung:M
CP-1
(+),M-C
SF,IL-1β
,TNF-α,N
F-κB
(+++),expression
ofTIM
P-1
↑,expression
ofMMP-9,M
MP-12(++)
Lung:collagenandelasticfiberdepo
sition
(++)
BALF
:eosino
phils
↑
Kaveh
etal.[117]
Portulacaoleracea
leaves,70%
ethano
lextract
1,2and4mg/mLin
drinking
water
for21
days
MaleWistarrats,about
220g
Asthm
aratssensitized
ondays
1,2,and3
by1mg/kg
ofovalbu
min
(OVA)+100mg
Al(OH) 3,i.p.,andexpo
sedto
1%OVAaerosol
for20
min
ondays
6,9,12,15,18,and
21Serum:thiol,SOD,C
AT↓,NO2- ,
NO3- ,
MDA↑
Blood
:lym
phocytes↓,totalW
BC,eosinop
hils,
neutroph
ils↑
Serum:thiolandMDA(0
1,+2,++4),SOD(0
1,+2,+++4),C
AT(0
1,++2and4),N
O2-(++
1,+++2and4),N
O3-(++alld
oses)
Blood
:neutrop
hilsandlymph
ocytes
(01,++2,
+++4),eosinop
hils(0
1,+++2and4),total
WBC(+++alld
oses)
Not
stud
ied
Wangetal.[119]
Salviamiltiorrhiza
Bge.f.albaroot
aqueou
sextract
4.6or
14g/kg
b.w.d
ailyin
thedrinking
water,21days
afterMCT
MaleSprague-Daw
leyrats,200-220
g
Pulmon
aryhypertension
anim
almod
elcaused
bymon
ocrotalin
e(M
CT)—
asingle
dose
of60
mg/kg
b.w.,s.c.
Meanpu
lmon
aryartery
pressure,right
ventricularsystolicpressure
↑Plasm
a:NO,6-K
eto-PGF1
α↓,
ET-1
andTXB2↑
Lung:T
GF-β1↑
Meanpu
lmon
aryartery
pressure
andright
ventricularsystolicpressure
(++both
doses)
Plasm
a:6-Keto-PGF1
αandTXB2(++both
doses),N
O,E
T-1
(++4.6,+++14)
Lung:T
GF-β1(++both
doses)
Not
stud
ied
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(+):aslight
beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no
beneficialeffect;(-):intensification
oftheharm
fuleffect.
31Oxidative Medicine and Cellular Longevity
Table14:T
heprotective
effectsof
plantorigin
materialsin
lipid
profi
ledisturbances.
Reference
Plant
extract,do
se,w
ayandtimeof
treatm
ent,andanim
als
Indu
cing
factor
andnegative
effects
Protectiveeffectsof
plantmaterial
Effectsof
plant
perse
deToledoEspindo
laetal.[121]
Cam
poman
esia
adam
antium
root
aqueou
sextract
200mg/kg
b.w.,p.o.,8
weeks
after
hyperlipidem
iaWistarrats,60days,140-150
g
Hyperlip
idem
iaindu
cedby
high
fructose
dietfor16
weeks
Bod
yweightgain:↑
Serum:T
C,T
G↑
Bod
yweightgain:(++du
ring
theexperiment,
+in
theend)
Serum:T
C,T
G(+++)
Not
stud
ied
Veber
etal.[34]
Brassicaoleracea
L.redcabbage
aqueou
sextract
125or
250mg/kg,p
.o.,twiceaday,
for3days
MaleWistarrats,200-300
g
Hyperlip
idem
iaindu
cedby
asingleadministrationof
TritonWR-1339
400mg/kg,i.p.
Serum:M
DA,P
C↑
RBC:SOD↑,CAT↓
Liver:MDA,P
C,SOD,G
Px↑,CAT↓
Kidney:MDA,P
C,G
Px↑,SO
D,C
AT↓
Cerebralcortex:SO
D↓,MDA,P
C↑
Hippo
campu
s:SO
D,C
AT↓,GPx,MDA↑
Serum:M
DA(0
both
doses),P
C(0
125,+++250)
RBC:C
AT(0
125,+++250),SOD
(+++both
doses)
Liver:CAT(0
125,+++250),P
C(+++125,++250),
MDA,SOD,G
Px(+++both
doses)
Kidney:MDA(0
both
doses),G
Px
(0125,+++250),
PC,SOD,C
AT(+++both
doses)
Cerebralcortex:SO
D(0
125,+++250),P
C(++125,+++250),M
DA(+++both
doses)
Hippo
campu
s:SO
D(0
125,+++250),M
DA
(++125,+++250),C
ATandGPx
(+++both
doses)
Not
stud
ied
Khlifi
etal.[120]
EricamultifloraL.
leafmethano
licextract
Pretreatm
ent150or
250mg/kg,i.g.,
1ho
urbefore
TritonWR-1339
MaleWistarrats,150-200
g
TritonWR-1339-indu
cedhyperlipidem
ia,a
single
dose
300mg/kg,i.p.
Serum:H
DL-c↓,TC,T
G,V
LDL-c,LD
L-c↑
Plasm
a:ALT
,AST
↑Liver:SO
D,G
Px,CAT↓,MDA↑
Liver:totalD
NAdamage↑
Serum:H
DL-c(0
150,++250),T
G,
VLD
L-c,LD
L-c
(++both
doses),T
C(++150,+++250)
Plasm
a:ALT
(++150,+++250),A
ST(+++both
doses)
Liver:SO
D(+
150,++250),M
DA
(++both
doses),
GPx(+
150,+++250),C
AT(++150,++250)
Liver:totalD
NAdamage(++both
doses)
250mg/kg
only
stud
ied:
Serum:V
LDL-c,
TG↑
Liver:SO
D↑
Onyenibeetal.[122]
Monodoramyristica
fruitaqueou
sextract
100or
200mg/kg
b.w.,p.o.,fi
vetimes
aweekfor8weeks
MaleWistaralbino
rats,120-140
g
Hypercholesterolemiaindu
cedby
cholesterol,p.o.
40mg/kg/0.3mL,
five
times
aweekfor8weeks
Serum:H
DL-c↓,LD
L-c,TC,T
G,A
ST,A
LT↑
Liver:SO
D,C
AT,G
SH↓,MDA↑
Heart:SOD,C
AT↓,MDA↑
Serum:L
DL-c(0
100,+200),A
ST,T
C(++both
doses),T
G,A
LT(+++both
doses),
HDL-c(↑
both
doses)
Liver:MDA(++both
doses),SOD,C
AT,
GSH
(+++)both
doses
Heart:M
DA(++100,+++200),SOD
(+++)both
doses,CAT(↑
both
doses)
Not
stud
ied
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(+):aslight
beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no
beneficialeffect.
32 Oxidative Medicine and Cellular Longevity
Table15:T
heprotective
effectsof
plantorigin
materialsin
anischaemia/reperfusion
mod
el.
Reference
Plant
extract,do
se,w
ayandtimeof
treatm
ent,andanim
als
Indu
cing
factor
andnegative
effects
Protectiveeffectsof
plantmaterial
Effectsof
plantperse
Casku
rlu
etal.[124]
Nigella
Sativa
seedsoil
Pretreatm
ent,asingledo
seof
400mg/kg
p.o.,3
days
before
reperfusion
MaleSprague-Daw
leyrats,250-300
g,10-12weeks
Renalreperfusioninjury
45min
occlusionof
thebilateralrenalpedicles
+reperfusion(24h)
Kidney:tubu
lointerstitialdamage↑,glom
erular
injury
score↑,GPx,CAT↓,MDA↑
Kidney:tubu
lointerstitialdamage(++),
glom
erular
injury
score(++),GPx,CAT,
MDA(++)
Not
stud
ied
Sravanthiand
Rao
[126]
Pentapetes
phoeniceamethano
licextract
Pretreatm
ent,for10
days
100,200or
400mg/kg/day
MaleWistarrats,300–350
g
Globalcerebralischemiaindu
cedby
tempo
rary
bilateralcarotid
artery
occlusion(30min)
andsubsequent
4hreperfusion
Brain:w
eight,water
andproteincontent,infarct
volumeandLP
O↑,SO
D,C
AT,G
SH,G
Px,GR,G
ST↓
Brain:w
eight,water
andproteincontent,
infarctvolume,MDA,SOD,C
AT,G
SH,
GPx,GR,G
ST(++alld
oses)
The
greaterthedo
sethebetter
theeffect
Not
stud
ied
Cakir
etal.[123]
Hypericum
perforatum
80%
ethano
lextract
50mg/kg,i.p.,at
thebeginn
ingof
ischem
iaMaleSprague-Daw
leyrats,300–350
g
Right
neph
rectom
yandsubsequent
ischaemia
(45min)/reperfusion(3h)
oftheleftkidn
eySerum:B
UN
andcreatinine
↑Kidney:CAT,SOD,G
Px↓,MDA↑
Kidney:hydrop
icchanges,tubu
lardilation
,tubu
lardesquamationcongestion
↑
Serum:B
UN
andcreatinine
(-)
Kidney:CAT,SOD,G
PxandMDA(+++)
Kidney:tubu
lardesquamationcongestion
,hydrop
icchanges,tubu
lardilation
(++)
Not
stud
ied
God
inho
etal.[125]
Trichiliacatiguaethyl-acetatefraction
ofaceton
e-water
(7:3)extract
200mg/kg,0.5hbefore
and1haftersurgery
(totaldo
se400mg/kg),p.o.
MaleWistarrats,3-m
onth-old
Cerebralischaem
ia-reperfusion
4-VO
mod
elof
transientglobalcerebralischaemia,15min
ischaemia
Brain:G
SH,G
SH/G
SSG,C
AT,SOD
↓,GSSG, P
CG,M
DA↑
Brain:C
AT(0),GSH
,GSSG,G
SH/G
SSG,
SOD,P
CG,M
DA(+++)
Not
stud
ied
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no
beneficialeffect;(-):intensification
oftheharm
fuleffect.
33Oxidative Medicine and Cellular Longevity
Table16:T
heprotective
effectsof
plantorigin
materialsin
anim
almod
elsof
diabetes.
Reference
Plant
extract,do
se,w
ayandtimeof
treatm
ent,andanim
als
Indu
cing
factor
andnegative
effects
Protectiveeffectsof
plantmaterial
Effectsof
plantper
se
Ben
Salem
etal.[128]
Cynarascolym
usleaves
75%
ethano
lextract
200or
400mg/kg
b.w.d
aily,p
.o.,
for28
days
MaleWistarrats,10-12-w
eek-old,
160–200g
Alloxanmon
ohydrate-ind
uced
diabetes,a
singledo
se150mg/kg
b.w.,i.p.
Bod
yweightgain:↓
Blood
glucose:↑
Serum:α
-amylase,pancreaticlip
ase,ALT
,AST
,ALP
,urea,CR↑
Plasm
a:TG,T
C,L
DL-c↑,HDL-c↓
Blood
:RBC,W
BC,H
GB,P
LT↓
Liver:SO
D,C
AT,G
SH↓,MDA,A
OPP↑
Pancreas:SO
D,C
AT,G
SH↓,MDA,A
OPP↑
Kidney:SO
D,C
AT,G
SH↓,MDA,A
OPP↑
Bod
yweightgain:(+++both
doses)
Blood
glucose:(+++200,++400)
Serum:A
LP(++both
doses),u
rea(++200,+++400),
CR(+++200,++400),A
LT,A
ST,α
-amylase,
pancreaticlip
ase(+++both
doses)
Plasm
a:TG,T
C,L
DL-c,HDL-c(+++both
doses)
Blood
:WBC(0
200,++400),P
LT(++both
doses),
RBCandHGB(+++both
doses)
Liver:MDA,SOD,C
AT,A
OPP(+++both
doses),
GSH
(+++200,↑400)
Pancreas:SO
D(++both
doses),M
DA,C
AT
(+++200,++400),G
SH,A
OPP(+++both
doses)
Kidney:SO
D(+
200,++400),C
AT(+++200,++400),
GSH
,MDA,A
OPP(+++both
doses)
Not
stud
ied
Dra
etal.[127]
Carallumaeuropaea
aerialpartextract
obtained
bysuccessive
extraction
with
dichloromethane
andmethano
l250or
500mg/kg
b.w.,p.o.,a
singledo
se,
followed
for10
hSw
issalbino
mice,8weeks
Alloxanmon
ohydrate-ind
uced
diabetes
type
1,asingledo
seof
200mg/kg
b.w.,i.p.
Blood
:glucose
↑Isletsdiam
eter:↓
The
lower
dose:
Blood
glucose:after2,4,and6h(++),after8
h(+++)
andafter10
h(↓);isletdiam
eter
(++)
The
higher
dose:
Blood
glucose:after2(++),after4and6h
(+++),after8and10
h(↓)
Not
stud
ied
Silvaetal.[59]
Musa×paradisiacaL.greenbanana
pasta
Com
mercialfeed
containing
25,50,or
75%
ofgreenbanana
pasta,for12
weeks
MaleWistarrats,6-8
weeks
old,180-300g
Alloxan-indu
ceddiabetes,type1,i.p.,asingle
dose
of150mg/kg
Serum:glucose,A
LT,A
ST,T
C,T
G,
fructosamine↑
Liver:totallipids,LP
OandPC↑
Kidney:PC↑
Serum:A
ST(0
alld
oses),glucose,fructosamine(+
25and50,+
++75),TC(0
25,+
++50,0
75),ALT
(025,+
++50
and75),TG(+++alld
oses)
Liver:totallipids(+
25and50,+
++75),LP
O(0
25,+
++50,↓
75),PC(0
25,+
+50,+
++75)
Kidney:PC(0
25,+
++50,↓
75)
Not
stud
ied
Duetal.[66]
Polysaccharideseparatedfrom
Lycium
barbarum
100,250,or
500mg/kg,p
.o.,for4weeks
MaleSpragueDaw
leyrats
8weeks
old,
180–220g
High-fatdietfor8weeks
andthen
diabetes
indu
cedby
streptozotocin
injection,
30mg/kg
foraweek
Fastingbloodglucose:↑
Serum:insulin,SOD,G
Px↓,BUN,IL-2,IL-6,
TNF-α,INF-α,M
CP-1,ICAM-1
↑Urine:A
LB↑
Fastingbloodglucose:(+
100,++250,and500)
Serum:INF-α(0
100and250,++500),insulin,IL-2,
ICAM-1
(0100,+250,++500),SOD,T
NF-α,B
UN
(0100,+250,+++500),G
Px,IL-6
(0100,+++250and
500),M
CP-1
(+250,+++250and500)
Urine:A
LB(+
250,++250and500)
Not
stud
ied
Wattanathorn
etal.[42]
The
combination
of50%
hydroalcoh
olic
extractsof
Man
gifera
indica
L.seedsand
Polygonu
modoratum
L.aerialparts
prepared
ataratio1:5
2,10,or50
mg/kg
b.w.,daily,for
10weeks
MaleWistarrats,180–220
g
Diabetescataractandretino
pathyindu
cedby
asingleinjectionof
streptozotocin
55mg/kg
b.w.
Blood
glucoseafter5and10
weeks
↑Grade
ofcataractseverity
↑Totalretinalthickness
↓Lens:SOD,C
AT,G
Px↓,MDA,V
EGF,ERK1/2,
p38M
APK,A
R↑
Lens:opacity
index↑
Blood
glucoseafter5weeks:(+2and50,+
+10)
Blood
glucoseafter10
weeks:(+2,010,-
50)
Totalretinalthickness:(++2and10,0
50)
Grade
ofcataractseverity:(++alld
oses)
Lens:SOD(++2,+10,-
50),MDA(++2and10,0
50),
GPx(+
2and50,++10),CAT,A
R,ERK1/2,p38M
APK
(++alld
oses),VEGF(+
2,++10,+
++50)
Lens:opacity
index(++alld
oses)
Not
stud
ied
34 Oxidative Medicine and Cellular Longevity
Table16:C
ontinu
ed.
Reference
Plant
extract,do
se,w
ayandtimeof
treatm
ent,andanim
als
Indu
cing
factor
andnegative
effects
Protectiveeffectsof
plantmaterial
Effectsof
plantper
se
Balbaa
etal.[57]
Nigella
sativa
seed
oil
2.0mL/kg
b.w.,i.g.,for21
days
after
diabetes
developm
ent
MaleWistarrats,about
125g
Type2diabetes
indu
cedby
ahigh-fat
dietfor2
weeks,followed
byasingleinjectionof
streptozotocin
35mg/kg,i.p.
Serum:T
NF-α,IL-6,AGE↑
Brain:T
BARS,XO,N
O,T
NF-α,IL-6,IL-1β,
iNOS,AGE,A
ChE
,Aβ-42,ID
E↑,GSH
,GPx,
GST
,SOD,glucose
↓
Serum:T
NF-α,IL-6(+++),AGE↓
Brain:A
ChE
(↓),TBARS,XO,IL-6,IL-1β(++),NO,
TNF-α,iNOS,GSH
,GST
,SOD,A
GE,A
β-42,ID
E,
glucose(+++),GPx(↑)
Serum:IL-6
andAGE↓
Brain:A
ChE
and
Aβ-42↓,TBARS,
NO,IDE,G
Px,
GST
,SOD↑
Fajri
etal.[131]
Equisetumarvenseaerialparts,methano
licextract
250or
500mg/kg
b.w.,daily
p.o.,for
45days
afterdiabetes
indu
cing
Malemice,6-8weeks
Streptozotocin-ind
uced
diabetes,
50mg/kg
b.w.i.p.,for5days
Sperm:viability,motility
↓,percentage
ofmorph
ologicalabno
rmalities,DNAdamage
andnu
clearim
maturity↑
The
lower
dose:viability,percentage
ofmorph
ological
abno
rmalitiesandDNAdamage(++),motility
and
percentage
ofnu
clearim
maturity(+++)
The
higher
dose:viability,motility
(++),percentage
ofmorph
ologicalabno
rmalities,DNAdamageand
nuclearim
maturity(+++)
Not
stud
ied
Khanra
etal.[129]
Abrom
aau
gustaL.
leaf
methano
lextract
100or
200mg/kg,p
.o.,daily
for4weeks
MaleWistarrats,2–3-m
onth-old,
abou
t180g
Type2diabetes
indu
cedby
asingleinjectionof
streptozotocin
65mg/kg
i.p.,15
min
later
nicotinamide110mg/kg,i.p
.Fastingbloodglucose:↑
Serum:H
DL-c,insulin
↓,TC,T
G,H
bA1c,
ALT
,AST
,urea,LD
H,C
K,C
RP↑
Kidney:DNAfragmentation
,ROS,TBARS,PC,
IL-1β,IL-6,TNF-α,↑,totalcoenzymes
Q9and
Q10,G
SH,C
AT,SOD,G
ST,G
Px,GR,G
6PD,
ATP,B
cl-2/Bax
↓Kidney:expression
ofNF-κB
,PKC(α,β
,δ,ε),caspase3,caspase9↑
Heart:R
OS,TBARS,PC,IL-1β
,IL-6,TNF-α,
GPx,GR,D
NAfragmentation
↑,total
coenzymesQ9andQ10,G
SH,C
AT,SOD,G
ST,
G6P
D,A
TP,B
cl-2/Bax
↓Heart:expressionof
NF-κB
,caspase
3,caspase9,PKC(α,β
,δ,ε)↑
Fastingbloodglucose:(++both
doses
Serum:T
C,T
G,H
bA1c,A
LT,A
ST,u
rea,LD
H,
CK,C
RP,insulin
(++both
doses),
HDL-c(++100,+++200)
Kidney:ROS,TBARS,PC,totalcoenzymeQ9,SO
D,IL-
1β,IL-6,TNF-α,D
NAfragmentation
,ATPandBcl-
2/Bax
(++both
doses),totalcoenzymeQ10,G
SH,
GST
,GPx,GR,G
6PD(++100,+++200),C
AT
(+++both
doses)
Kidney:expression
ofNF-κB
,PKC(α,β
,δ,ε),
caspase3,caspase9(++both
doses)
Heart:R
OS,TBARS,PC,G
SH,C
AT,SOD,IL-1β
,IL-6,
TNF-α,A
TP,B
cl-2/Bax,D
NAfragmentation
(++both
doses),G
ST,G
6PD(++100,+++200),totalcoenzymes
Q9andQ10
(+++both
doses),G
Px,GR(↑
both
doses)
Heart:expressionof
PKC(α,β
,δ,ε),caspase3,caspase
9(++both
doses),N
F-κB
(+++both
doses)
Not
stud
ied
Omod
anisi
etal.[130]
Moringa
oleifera
leafextractobtained
bysuccessive
extraction
withn-hexane
and
80%
methano
l,250mg/kg
b.w.,p.o.,
for6weeks
MaleWistarrats,10weeks
Streptozotocin-ind
uced
diabetes,a
singledo
seof
55mg/kg,i.p.
Plasm
a:glucose↑
Serum:T
P,A
LB↓
Kidney:weightandrelative
weight↑
Kidney:GPx,SO
Dslightly↓,CAT↓,
TNF-αslightly↑,
MDA,IL-6↑
Plasm
a:glucose(++)
Serum:A
LB(+),TP(+++)
Kidney:weightandrelative
weight(++)
Kidney:GPx(-),CAT(0),TNF-α,IL-6(+),
SOD(++),MDA(+++)
Plasm
a:glucose↓
Serum:T
P,A
LB↑
Kidney:SO
D↑,
GPx,IL-6,
TNF-α↓
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(+):aslight
beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no
beneficialeffect;(-):intensification
oftheharm
fuleffect.
35Oxidative Medicine and Cellular Longevity
the protective effect of plant preparations which involvedimprovement of oxidative balance by activation of theNrf2/HO-1 antioxidant pathway [61] and the amelioratingeffect on lipid status [132, 133]. The latter was also confirmedin vitro as the lipolysis-promoting influence in 3T3-L1 cellswas observed [61]. In mice fed a high-fat diet, coadministra-tion of Euterpe oleracea extract reversed the changes of lipo-genic proteins expression in the liver. Additionally, theinvestigated preparation increased hepatic expression ofABCG5 and ABCG8 transporters responsible for removingexcess of cholesterol by secretion into bile [43].
The detailed results of the performed studies are collectedin Table 17.
2.10.9. The Protective Influence of Plant Preparations againstGastric Ulcer-Inducing Factors. The gastric ulcers areregarded as the most common disease of gastrointestinaltract, but they can be caused by many various factors. Ther-apy of different disorders with using nonsteroidal anti-inflammatory drugs like indomethacin and excessiveconsumption of alcohol belong to important ones [45, 134].As pharmaceutical agents are not fully effective and theirapplication may also be connected with development of sideeffects, an alternative ways of treatment became the subjectof research. Plant origin substances showed a wide rangeof beneficial effects, including alleviated or reversed oxida-tive stress which was found to be involved into gastriculcer etiology as well as mechanism of indomethacintoxicity [135–137].
The detailed results of the performed studies are pre-sented in Table 18.
2.10.10. The Protective Effects of Plant Origin Materials inAnimal Model of Different Disorders. The symptoms of manyother various disturbances were affected in a positive way byusing plant materials of experimentally confirmed antioxi-dant properties and containing acknowledged antioxidantslike phenolic acids and flavonoids [36, 41, 138]. A wide rangeof diseases: lithiasis, thyroid disorders, retinal degeneration,irritable bowel syndrome, hyperthyroidism, periodontitis,and mammary gland hyperplasia, were studied, pointing togreat possibilities “hidden” in plant origin agents.
The details of the performed studies are presented inTable 19.
2.11. The Protective Effects of Plant Origin Materials againstRadiation. Plant extracts also showed some efficacy againstradiation-induced damage. The research revealed theinvolvement of JAK-STAT pathway into the mechanism ofthe protective influence on the hematopoietic system [70].Animal studies also showed the reversing effect of plantmaterial on the disturbances of antioxidant defence causedby γ-radiation in blood and organs [145, 146]. One of therecent in vitro investigations, performed on keratinocytecells, confirmed the antioxidant action of a plant preparationagainst UVB radiation, which could contribute to develop-ment of new skin protective strategies [147].
The details of the performed studies are presented inTable 20.
3. The Comparison of Plant Preparations withStandard Drugs and Supplements: TheDependence of Effects on Treatment Wayand Doses
The effects of plant origin materials were often investigatedin comparison with those shown by standard drugs. Theresults clearly show that there may be a possibility to replacedifferent medicines with plant preparations which do notcause so many severe side effects, but the detailed researchmust be performed before the final conclusions can be made.
The question of advantage of plant origin extracts overany standard drug is complicated, and a univocal answer isvery difficult as in some cases the differences in the influenceof the compared agents were strongly dependent on theapplied dose [45, 135] and studied parameters [115, 129].
Hamm et al. [116] found that hops (Humulus lupus L.)flavonoid-rich extract protected against ovariectomy-induced visceral adiposity and increase in liver triglyceridesobserved in 7-month-old retired breeder C57BL/6 mice.However, particularly in case of the former parameter, theobserved effect was not so distinct as that noted in animalsreceiving 17-β-estradiol. Additionally, hops extract couldnot prevent the loss of uterus weight caused by the surgerywhile estrogen showed quite a considerable reversing effect.
Leung et al. compared the effect of black tea extract withthat exerted by estrogen in ovariectomized rats. The resultswere characterized by a considerable diversity. In case ofbody weight reduction, estradiol’s benefit influence wasmuch better. In contrast, aortic cGMP and serum TC andpeNOS, NOX2, NOX4, and ROS generation in the aorta wereaffected in similar or even entirely the same way by bothagents. Additionally, in case of serum TG the plant materialsproved to possess much better ability to restore the valuesobserved in sham-operated control animals [115].
3.1. The Comparison of Crude Extracts and the ParticularSubstances Separated from Plant Materials. The plant extractcan show better properties than particular compoundsadministered alone as there may occur some synergisticeffects among its components. Such an assumption couldbe supported by the results reported by He et al. [148] whocompared the influence of Paeonia suffruticosa seed extractand 10 compounds (oligostilbenes) isolated from it withusing an in vitro IL-1β-induced osteoarthritis model. In thestudy performed on rabbit chondrocytes, IL-1β caused a sig-nificant decrease in viability and 10 studied components usedalone showed an improving effect, but the intensity of thiseffect was markedly different, depending on the structure.However, the application of the extract containing all the oli-gostilbenes showed the best effect, comparable with thatobserved for diacerein—a drug of IL-1β-inhibition action,used in osteoarthritis therapy. Such results made the authorssuggest the possibility of synergism among the particularoligostilbenes.
3.2. Plant Preparations as Lipid Profile Regulating Agents –The Comparison with Standard Drugs. Plan preparationswere studied in regard to the possibility of their application
36 Oxidative Medicine and Cellular Longevity
Table17:T
heprotective
effectsof
plantorigin
materialsin
anim
almod
elsof
obesity.
Reference
Plant
extract,do
se,w
ayandtimeof
treatm
ent,andanim
als
Indu
cing
factor
andnegative
effects
Protectiveeffectsof
plantmaterial
Effectsof
plant
perse
deOliveira
etal.[43]
Euterpeoleracea
Mart.(açaí)seed
hydroalcoh
olicextract
300mg/kg/d,i.g.,for12
weeks
MalemiceC57BL/6,4weeks
Diet-indu
cedobesity
60%
fatdietfor12
weeks
Epididymalandretrop
eriton
ealfat
mass↑
Bod
yweightgain↑
Liver/body
weight:↑
Glikaemia:↑
Plasm
a:adipon
ectin↓,leptin
↑Serum:T
C,T
G,L
DL,
VLD
L↑
Liver:SO
D,C
AT,G
Px↓,cholesterol,
TG,M
DA,P
C↑
Liverexpression
oflip
ogenicproteins:
pAMPK,p
ACC/A
CC↓,
SREBP-1c,HMG-C
oA-R
↑
Epididymalandretrop
eriton
ealfat
mass(++)
Bod
yweightgain
(++)
Liver/body
weight:(+++)
Glikaemia:(++)
Plasm
a:leptin,adipo
nectin
(+++)
Serum:T
C,T
G,L
DL,
VLD
L(++)
Liver:cholesterol,TG(++),SO
D,C
AT,G
Px,PC(+++),
MDA(↓),CAT(↑)
Liverexpression
oflip
ogenicproteins:p
AMPK,
SREBP-1c,HMG-C
oA-R,p
ACC/A
CC(+++)
Liver:TG↓,
SOD↑
Bud
riesietal.[133]
Castaneasativa
Mill
bark
extract
(ENC®,
SilvaT
eam
S.p.a.,San
Michele
Mon
dovì,Italy)
20mg/kg,p
.o.,for21
days
MaleSprague-Daw
leyrats,9-w
eek-
old,
270-300g
High-fatdietfor10
weeks
andthen
during
extractadministration
Bod
yweightgain:↑
Serum:T
C,L
DL-c,TG↑,HDL-c↓
Plasm
a:IL-1α,IL-1β
,IL-2,IL-5,IL-6,IL-7,
IL-12p70,IL-17A,IL-18,T
NF-α↑,
IL-4,IL-10,IL-13
↓Liver:SO
D,G
SSG-red,U
DPGT↓
Ileum:M
DA↑
Colon
:MDA↑
Bod
yweightgain:(++)
Serum:T
G(++),TC,L
DL-c,HDL-c(+++)
Plasm
a:IL-1β(-),IL-5,IL-18
(0),IL-7,T
NF-α(+),
IL-1α,IL-2,IL-6,IL-12pro70,IL-4,IL-10
(++),
IL-17A
,IL-13
(+++)
Liver:UDPGT(++),SO
D,G
SSG-red
(↑)
Ileum:M
DA(+++)
Colon
:MDA(++)
Liver:SO
D↑
Ileum:M
DA↑
ElA
yedetal.[132]
10%
ethano
lextractof
Vitisvinifera
grapeseed
(50%
)andskin
(50%
)500mg/kg
b.w.,i.p.,daily
for6weeks
MaleWistarrats,210–230
g
High-fatdiet(40%
fat,45%
carboh
ydrate,
15%
protein)
for6weeks
Bod
yandlung
weight:↑
Lung
lipid
content:↑
Plasm
a:adipon
ectin,
HDL-c↓,CRP,T
G,
TC,V
LDL-c,LD
L-c/HDL-c,LD
L-c↑
Lung:C
AT,SOD,Z
n,Mg↓,MDA,lipase,
Ca,Fe
↑
Bod
yandlung
weight:(+++)
Lung
lipid
content:(+++)
Plasm
a:CRPandadipon
ectin(++),TG,T
C,
VLD
L-c,LD
L-c,LD
L-c/HDL-c,HDL-c(+++)
Lung:M
DA(++),CAT,SOD,lipase,Mg,Zn,
Ca,Fe
(+++)
Plasm
a:TG,
TC,V
LDL-c,
LDL-c,HDL-c,
LDL-c/HDL-c
↓Lu
ng:Z
n↑,
MDA,M
g↓
Qiu
etal.[61]
Hedansanq
iTiaozhi
Tang(a
Chinese
herbalprescription
)contains
four
traditionalC
hinese
herbalmedicines:
Pana
xnotoginsengdryroot,Salvia
miltiorrhiza
Bun
gedryroot,C
rataegus
pinn
atifida
Bge.fruit,
Nelum
bonu
cifera
Gaertnleaf
350,700,1400
mg/kg/day,i.g.,
once
aday,for4weeks
MaleSprague-Daw
leyrats,180–190
g
Hyperlip
idaemiaindu
cedby
high-fat
diet
(2%
cholesterol,10%
lard,10%
eggyolk,0.5%
bilesodium
,77.5%
standard
diet(w
/w),for4weeks
Bod
yweight↑
Serum:T
C,T
G,L
DL-c,AST
,ALT
,MDA↑,
HDL-c,SO
D,C
AT,
GPx,T-A
OC↓
Liver:T-A
OC,SOD,C
ATandGPx↓,
TC,T
G,M
DA↑
Liver:steatosis,lobu
larinflam
mation,
hepatocellu
larballoon
ing↑
Bod
yweight:(+
350,++700and1400)
Serum:L
DL-c,TC,(+350,++700and1400),CAT(+
350,
+++700and1400),TG,G
Px(++350and700,+++1400),
T-A
OC,M
DA,SOD(++350,+++700and1400),
HDL-c,ALT
,AST
,(+++alld
oses)
Liver:MDA(+
350,+++700and1400),TC,T
G,
GPx(++350and700,+++1400),T-A
OC,C
AT
(++350,+++700and1400),SO
D(+++alld
oses)
Liver:steatosis(+
alld
oses),lobu
larinflam
mation
(++alld
oses),hepatocellu
larballoon
ing
(++350and700,+++1400)
4200
mg/kg
stud
ied:
none
37Oxidative Medicine and Cellular Longevity
Table17:C
ontinu
ed.
Reference
Plant
extract,do
se,w
ayandtimeof
treatm
ent,andanim
als
Indu
cing
factor
andnegative
effects
Protectiveeffectsof
plantmaterial
Effectsof
plant
perse
Shengetal.[33]
Morus
alba
var.multicaulis(Perrott.)
Loud
.(mulberry)
leaves
20%
mulberryleafpo
wderaddition
tohigh
fatdiet,13weeks
MaleC57BL/6J
mice,
4-week-old,
15-20g
Obesitycaused
byhigh
fatd
iet(60%calories
from
fat),providedbefore
(aroun
d8weeks)
anddu
ring
mulberryadministration
Bod
yweight,fatmass↑
BAT:bod
yweightratio↓
Fastingbloodglucoseandplasmainsulin
↑HOMA-IR↑
Serum:A
ST,C
R↑
Bod
yweight:(++beginn
ingfrom
6thweek
oftreatm
ent)
FatmassandBAT:bod
yweightratio(++),
fastingbloodglucoseandplasmainsulin
(++),HOMA-IR(+++)
Serum:A
ST,C
R(+++)
Not
stud
ied
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(+):aslight
beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no
beneficialeffect;(-):intensification
oftheharm
fuleffect.
38 Oxidative Medicine and Cellular Longevity
Table18:T
heprotective
effectsof
plantorigin
materialsin
anim
almod
elsof
gastriculcers.
Reference
Plant
preparation,
dose,w
ay,tim
eof
treatm
ent,andanim
als
Indu
cing
factor
andnegative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plantperse
Rtibi
etal.[135]
Ceratonia
siliqua
L.po
daqueou
sextract
Pretreatm
ent,500,1000,and
2000
mg/kg,b.w.,p.o.,
during
15days
MaleWistarrats,220–250
g
Ethanol
4g/kg,b.w.,p.o.,one
dose
Ulcer
index↑
Ulcer
mucus
volume↓
Stom
achmucosa:MDA,H
2O2↑,-SH
grou
ps,SOD,C
AT,G
Px↓
Ulcerindex:(++alldoses,a
decreasealon
gwithan
increaseddo
se)
Ulcer
mucus
volume:(++500and1000,+
++2000)
Stom
achmucosa:SO
D,C
AT(++500and1000,+
++2000);MDA
(++500and1000,+
++2000);H
2O2,-SH
grou
ps,G
Px
(0500,++1000,+
++2000)
Not
stud
ied
Chand
aetal.[45]
Paederia
foetidaL.
leafmethano
lextract
100,200mg/kg
b.w./d
ay,
for4days
Wistarrats,150-180
g
Indo
methacin-pylorusligation
indu
cedulcer
Indo
methacin25
mg/kg,s.c.,on
cedaily
for4days
+surgicalprocedure
onthe4thday
Gastricsecretion:
volume,acid
output
↑,pH
↓Ulcer
index:↑
Gastricsecretion:
volumeandacid
output
(++bo
thdo
ses),
pH(++100,+++200)
Ulcer
index:(++both
doses)
Not
stud
ied
Sabiuetal.[136]
Spondias
mom
binandFicus
exasperata
leafaqueou
sextracts
Pretreatm
ent
100or
200mg/kg
b.w.,
p.o.,for
21days
Wistarrats,about
180g
Indo
methacin-indu
cedgastric
ulceration
,asingledo
seof
30mg/kg
b.w.,p.o.
Ulcer
index:↑
Gastricsecretion:
acid
output
↑,pH
↓Stom
ach:
MDA↑,SO
D↓
Gastricjuice:pepsin
activity
↑,mucin
content↓
Ulcer
index:(++both
dosesof
both
extracts)
%ulcerinhibition
:(++both
dosesof
both
extracts)
Gastricsecretion:
acid
output
andpH
(++both
dosesof
both
extracts)
Ficusexasperata
Stom
ach:
MDA,SOD(++both
doses)
Gastricjuice:pepsin,m
ucin
(++both
doses)
Spondias
mom
bin
Stom
ach:
MDA,SOD(++both
doses)
Gastricjuice:pepsin,m
ucin
(++both
doses)
The
higher
dosesshow
edbetter
beneficialeffects
200mg/kg
b.w.only
stud
ied,
slight
effects
Gastricsecretion:
acid
output
↑,pH
↓Gastricjuice:mucin
content↓
Sattar
etal.[137]
Myristica
fragrans
seeds
70%
ethano
lextract
200mg/kg,anho
urbefore
ethano
l,on
ceadayfor15
days
Wistarrats,150-300
g
90%
ethano
l-indu
cedgastriculcers
5mL/kg
for15
days,onceaday
Gastriccontents:p
H↓,totalacidity
↑;averagenu
mberof
ulcers
peranim
al↑
Ulcer
index:↑
Gastriccontents:p
H↑,totalacidity
(++)
Average
numberof
ulcersperanim
al(++)
Ulcer
index:(++)
%ulcerinhibition
:(++)
Not
stud
ied
Raeesi
etal.[134]
Biebersteinia
multifida
root
70%
methano
lextract
Pretreatm
ent150or
300mg/kg,
p.o.,1
hbefore
ulcerindu
ction
MaleWistarrats,200-250
g
75%
ethano
l-indu
cedgastriculcer
4mL/kg,p
.o.
Ulcer
area/stomach↑;
Num
berof
ulcers/stomach↑;
Gastricmucosa:T-A
OC↓
Ulcer
area/stomach:
(+++both
doses)
Num
berof
ulcers/stomach:
(++both
doses)
Gastricmucosa:T-A
OC(↑
both
doses)
Not
stud
ied
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect.
39Oxidative Medicine and Cellular Longevity
Table19:T
heprotective
effectsof
plantorigin
materialsin
anim
almod
elsof
variou
sdiseases.
Reference
Plant
extract,do
se,w
ayandtimeof
treatm
ent,
andanim
als
Disorder,indu
cing
factor,and
negative
effects
Protectiveeffectsof
plantmaterial
Effectsof
plant
perse
Benhelim
aetal.[139]
Nigellasativa
L.seedsessentialo
il,5mL/kg
b.w.
from
1stto
28thor
from
15thto
28th
days,p
.o.
MaleWistarrats,120-130
g
Lithiasisindu
cedby
0.75%
ethylene
glycol
(EG)and1.0%
ammon
ium
chloride
indrinking
water
for28
days,first3
days
both,
then
onlyEG,for
25days
Bod
yweight:↓
Urine:M
g,Ca↓,oxalate,UA,p
hosphate↑
Serum:C
R,U
A,B
UN
↑Kidney:oxalate,Ca,ph
osph
ate↑
From
1stto
28th
Bod
yweight:(++)
Urine:C
a,Mg,oxalate,UA,p
hosphate(++)
Serum:C
R,U
A,B
UN
(++)
Kidney:oxalate,Ca,ph
osph
ate(++)
From
15stto
28th
Bod
yweight:(++)
Urine:C
a,Mg,oxalate,UA,p
hosphate(++)
Serum:C
R(+),UA,B
UN
(++)
Kidney:oxalate,Ca,ph
osph
ate(++)
The
latter
treatm
entshow
edworse
effects
Not
stud
ied
Chang
etal.[140]
Lycium
barbarum
fruitwater
extracts
Blend
ed:p
articles
3:58
±3:8
μm
Subm
icron:
particles100±
70nm
Dietary
pretreatment:250mg/kg
for54
days,p
.o.
MaleSprague-Daw
leyrats,8–10
week,200-300g
Retinaldegeneration
indu
cedby
whitecool
light,the
intensity1,400–1,500luxfor2
days,12hlight/12hdark
cycle
Retinalthickn
ess:↓
Retina:GSSG+GSH
↓,MDA↑
Subm
icronextract:retinalthickness
(++)
Retina:GSSG+GSH
↑,MDA(+++)
Blend
edextract:retinalthickness
(+)
Retina:GSSG+GSH
(++),MDA(+++)
Not
stud
ied
Cojocariu
etal.[141]
Chrysan
thellum
american
umpo
lyph
enolic
(butanol)fraction
of80%
ethano
licextract
100mg/kg
b.w.,i.g.,2days
during
and4days
afterstressparadigm
FemaleWistarratsabou
t200g
Irritablebowelsynd
romeanim
almod
elindu
cedby
multifactorialstressexpo
sure
paradigm
for7days
Tem
porallobe:SO
DandGPx↓,MDA↑
Tem
porallobe:SO
DandGPx,MDA(++)
Non
e
Sdayriaetal.[41]
Euphorbiaretusa
leafmethano
lextract
Pretreatm
ent200mg/kg,p
.o.
Swissalbino
mice,20–30g
Inflam
mation,
indu
cedby
1%carrageenan
(in0.9%
NaC
l)injectionof
100μLinto
the
subp
lantar
region
oftherighthind
paw
Hindpaw:M
DA↑,SO
D,C
AT,G
Px↓
Liver:SO
D,C
AT,G
Px↓
Hindpaw:M
DA,C
AT,G
Px,SO
D(++)
Liver:SO
D,C
AT,G
Px(++)
Not
stud
ied
Hatipoğlu
etal.[142]
Crataegus
orientalisM
Bieber.fruit70%
ethano
lextract
100mg/kg/day,orogastrically,atplacem
ent
oftheligature,for11
days
MaleWistarrats,aged4mon
ths,abou
t340g
Periodo
ntitiscaused
bysubm
erging
a4/0silk
ligaturein
thesulcus
ofthe
mandibu
larrightfirstmolarsof
rats,kept
subgingivally
foraperiod
of11
days
Serum:T
OS,OSI
↑,TAS↓
Interdentalareabetweenfirstandsecond
molars:inflam
matorycells,osteoclasts,
osteoblasts↑
Serum:T
OS,OSI,T
AS(+++)
Interdentalareabetweenfirstandsecond
molars:
osteob
lasts(0),inflam
matorycells
and
osteoclasts(++)
Not
stud
ied
40 Oxidative Medicine and Cellular Longevity
Table19:C
ontinu
ed.
Reference
Plant
extract,do
se,w
ayandtimeof
treatm
ent,
andanim
als
Disorder,indu
cing
factor,and
negative
effects
Protectiveeffectsof
plantmaterial
Effectsof
plant
perse
Kon
daetal.[138]
Azimatetracan
tharoot
95%
ethano
lextract
Pretreatm
ent250or
500mg/kg,p
.o.,60
min
priorto
glycerol
MaleWistaralbino
rats,150-250
g
Acuterenalfailure
caused
byhyperton
icglycerol,a
singledo
seof
8mL/kg,i.m
.,into
both
hind
limbs
Serum:C
R,B
UN
↑,TP,A
LB↓
Urine
output:↓
Kidney:SO
D,G
SH,G
R,G
Px,CAT↓
The
lower
dose:
Serum:T
P,C
R,B
UN,A
LB(++)
Urine
output:(++)
Kidney:GPx(0),CAT(+),SO
D,G
R(++),
GSH
(+++)
The
higher
dose:
Serum:T
P,A
LB(++),BUN,C
R,(+++)
Urine
output:(+++)
Kidney:SO
D,G
SH,G
R,G
Px,CAT(+++)
Only500mg/kg
stud
ied
Urinary
output:↑
Kidney:SO
D↓
Panth
etal.[36]
Salicorniaeuropaea
water
extract
1400
mg/kg/day
p.o.,for
6weeks
Malerats:spo
ntaneous
hypertensive
(SHR)rats
andSprague-Daw
ley,6weeks,about
200g
Vasculardysfun
ctionandhypertension
,NaC
l-indu
ced,
800mg/kg/day,p
.o.
for6weeks
SDrats:systolic
anddiastolic
pressure
↑SH
Rrats:systolic
anddiastolic
pressure
↑
SDrats:systolic
pressure
(+++),diastolic
pressure
(++)
SHRrats:systolic
pressure
(++),diastolic
pressure
(+)
Not
stud
ied
El-Kashlan
etal.[143]
Phoenixdactylifera
L.datepalm
pollen
(com
mercialprod
uct)
80%
ethano
lextract
150mg/kg,p
.o.,everydayfor56
days
MaleWistarrats,about
250g
L-thyroxine-indu
cedhyperthyroidism
300μg/kg,i.p.,everydayfor56
days
Weight:finalb
ody,testes,epididymis,
prostategland,
seminalvesicle↓
Serum:fT3,fT4,E2↑,LH
,FSH
,T,T
SH↓
Testis:SD
H,L
DH,A
LP,A
CP,G
6PD,C
AT,
SOD,G
Px,GR,G
SH↓,MDA,
NO,A
ST,A
LT↑
6-N-propyl-2-thiouracil-indu
ced
hypo
thyroidism
10mg/kg,i.p.,every
dayfor56
days
Weight:finalb
ody,testes,epididymis,
prostategland,
seminalvesicle↓
Serum:fT3,fT4,LH
,FSH
,T↓,E2,TSH
↑Testis:SD
H,L
DH,A
LP, A
CP,G
6PD,C
AT,
SOD,G
Px,GR,G
SH↓,MDA,
NO,A
ST,A
LT↑
Hyperthyroidism
Weight:finalb
ody,testes,epididymis,p
rostate
gland,
seminalvesicle(++)
Serum:fT3,TSH
,E2(++),fT4,LH
,FSH
,T(+++)
Testis:ALP
(++),SD
H,L
DH,A
CP,G
6PD,G
R,G
SH,
MDA,N
O,A
ST,A
LT,G
Px(+++),CAT,SOD↑
Hypothyroidism
Weight:finalb
ody,testes
(0),epididym
is,
prostategland,
seminalvesicle(++)
Serum:T
SH,fT3,fT4(0),E2(++),LH
,FSH
,T(+++)
Testis:ALP
,NO
(++),SD
H,L
DH,A
CP,G
6PD,G
R,
GSH
,MDA,A
ST,A
LT(+++),GPx,CAT,SOD
↑
Weight:prostate
gland,
epididym
is,
seminalvesicle↑
Serum:fT3,fT4↓
LH,T
,E2↑
Testis:SD
H,
LDH,G
R,C
AT,
SOD,G
Px,GSH
↑,MDA,N
O↓
You
etal.[144]
Ferm
entedpapaya
extracts(obtainedby
ferm
entation
ofpapaya
throughAspergillu
soryzae
for3mon
thsandthen
for3mon
thsusing
Saccharomyces
cerevisiae
yeasts)
30,15or
5mL/kg.p
.o.,days
1–30
FemaleSP
FSprague-Daw
leyrats,
180–200g,7-8weeks
Mam
maryglandhyperplasiaindu
cedby
estrogen
andprogestin,
0.5mg/kg
ofestradiolb
enzoate
Days1-25
and4mg/kg
ofprogestin
days
26–30,i.m
.Serum:E
2,progesterone,L
H,F
SH,M
DA,
AST
,totalbilirub
in↑;GPx,SO
D,A
LT↓
Liver:MDA↑;GPx,SO
D↓
Mam
marygland:
GPx,SO
D↓,
hyperplasia,MDA↑
Serum:M
DA(0
5,++15
and30),progesterone
(+5and
15,+
+30),totalb
ilirubin(0
5,++5,+++30),E2(++all
doses),LH(+
5,++5,+++30),FSH,A
LT,A
ST(++5and
15,+
++30);GPxandSO
D(0
5,+++15
and30)
Liver:MDA(0
5,++15
and30),GPx,SO
D(0
5,++15,+
++30)
Mam
marygland:
hyperplasia(0
5,+15,+
+30),MDA,
GPx(0
5,++15
and30),SO
D(0
5,+++15
and30)
Only30
mL/kg
stud
ied
Serum:SOD
↑Liver:SO
D↑
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(+):aslight
beneficialeffect;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect;(0):no
beneficialeffect.
41Oxidative Medicine and Cellular Longevity
Table20:T
heprotective
effectsof
plantpreparations
againstradiation.
Reference
Plant
preparation,
dose,w
ayandtimeof
treatm
ent,anim
als
The
dose
andnegative
effects
Protectiveeffectsof
plantpreparation
Effectsof
plantper
se
Don
getal.[70]
Spatholobu
ssuberectus
Dun
n(Ji-Xue-TengBeijin
gLvye
Pharm
aceuticalC
o.Ltd.,C
hina)75%
ethano
lextract
40g/kg,p
.o.,for21
consecutivedays
afterirradiation
Chinese
Kun
Ming(K
M)mice,6–8weekaged
60Coγ-radiation,
ado
seof
6Gy
Bod
yweight:↓
Blood
:WBC,R
BC,P
LT,H
GB↓
Bon
emarrowtissue:B
cl-2
expression
,ph
osph
orylationof
JAK2andST
AT5a
↓Liver:ROS,MDA↑,SO
D,G
Px↓
Femur:bon
emarrowcells
↓
Bod
yweight:(+++)
Blood
:WBC,P
LT,H
GB(++),RBC(+++)
Bon
emarrowtissue:p
hospho
rylation
ofJA
K2(++),
phosph
orylationof
STAT5a
andBcl-2
expression
(+++)
Liver:ROS,MDA(++),SO
D,G
Px(+++)
Femur:bon
emarrowcells
(++)
Not
stud
ied
Jeenaetal.
[145]
Zingiberoffi
cina
leR(ginger)essentialo
il(K
ancore
IngredientsLimited,A
ngam
ali,Kerala,India)
100or
500mg/kg
b.w.p
.o.,5-daypretreatment
andthen
for14
days
MaleBalb/Cmice,6-8week
γ-Radiation
,6Gy,who
lebody
expo
sure
Blood
:WBC,H
GB↓
Intestinalmucosa:SO
D,C
AT,
GPx,GSH
↓
Blood
:WBC(++),HGB(+++)
Intestinalmucosa:SO
DCAT,G
PxandGSH
(++100,+++500)
Not
stud
ied
Khattab
etal.[146]
Boragooffi
cina
lisL.
seedsoil
Posttreatment:50
mg/kg
b.w./d
ay,p
.o.,3ho
urs
afterirradiationandfor2weeks
Pretreatm
ent:50
mg/kg
b.w./d
ay,p
.o.,on
eweekbefore
irradiationandfor2weeks
Malealbino
rats,160-180
g
γ-Radiation
asinglesublethald
oseof
6.5Gy
ofwho
lebody
Serum:G
SH,H
DL-c↓,AST
,ALT
,GGT,
MDA,T
G,T
C,L
DL-c↑
Liver:GSH
↓,MDA↑
Posttreatment:
Serum:A
ST,A
LT(++),GGT,M
DA,T
G,T
C,
GSH
,LDL-c,HDL-c(+++)
Liver:GSH
(++),MDA(+++)
Pretreatm
ent:
Serum:A
ST,A
LT(++),GGT,M
DA,T
G,T
C,
GSH
,LDL-c,HDL-c(+++)
Liver:GSH
(++),MDA(+++)
Non
e
Wang
etal.[147]
Rub
usidaeus
redraspberryethano
licextract
750μg/mLappliedon
thedo
rsalregion
ofthe
nude
mice1daybefore
UVBandthen
for5days
Femalenu
demice(ICR-Foxn/nu
strain)
UVB30
mJ/cm
2in
thedo
rsalregion
,on
ceadayfor5days
Totaldo
seof
150mJ/cm
2permou
seSkin
epidermalthickn
ess:↑
Transepidermalwater
loss↑
Erythem
a↑
Skin:C
OX-2,D
NAoxidationand
proteincarbon
ylation↑
Skin
epidermalthickn
ess:(+++)
Transepidermalwater
loss
(++)
Erythem
a(++)
Skin:C
OX-2,D
NAoxidation(++),protein
carbon
ylation(+++)
Not
stud
ied
↓:adecrease
vs.con
trol;↑:anincrease
vs.con
trol;(++):adistinctbeneficialeffect;(+++):acompletebeneficialeffect.
42 Oxidative Medicine and Cellular Longevity
as lipid profile normalizing agents, and the results seem to beauspicious [120–122]. Additionally, the researchers per-formed comparisons with standard drugs. The outcomesshowed that the efficacy of plant material needs not be worsethan that showed by acknowledged pharmaceutical agents.However, it should be emphasized that the final effects maybe different, depending on the applied dose.
Veber et al. [34] compared the effects of two doses (125 or250mg/kg) of aqueous extract of red cabbage with thatshowed by fenofibrate, a drug used in therapy of abnormallipids in the blood, on oxidative stress parameters in rats withhyperlipidemia caused by Triton WR-1339. Although thehigher dose proved to possess protective properties generallycomparable with the drug, the lower one in some casesshowed no efficiency.
Erica multiflora L. leaf methanolic extract (150 or250mg/kg) effect was studied in rats with Triton WR-1339-induced hyperlipidemia in comparison with fenofibrate tak-ing into account chosen lipid and antioxidant parameters.The higher dose showed comparable or even better protectiveaction than the medicine. In contrast, total DNA damage wasalleviated much better by the used drug [120].
Onyenibe et al. [122] investigated the efficiency of twodoses of Monodora myristica aqueous extract as a protectiveagent in case of deterioration of lipid profile and oxidativeparameters in hypercholesterolemic rats and compared theobtained results with those noted for a standard drug Ques-tran. The authors found that generally two doses of plantpreparation, namely, 100 and 200mg/kg b.w., showed a bet-ter influence.
The effects of lipid-lowering drugs simvastatin and cipro-fibrate as well as aqueous extract of Campomanesia adaman-tium O. Berg root were compared in rats with high-fructosediet-induced hyperlipidemia. The plant material exerted theentirely comparable influence in case of lipid parametersand even better as regards body weight gain lowering [121].
3.3. The Comparison of Plant Extracts of HepatoprotectiveProperties with Pharmaceutical Agents. Liu et al. [51] com-pared the protective action of pretreatment with Sonneratiaapetala fruit water extract (100, 200, and 400mg/kg) againsthepatic damage caused by acetaminophen in mice with theeffect of an acknowledged antidote NAC (N-acetyl-L-cyste-ine). The scientists observed the protective influence of plantpreparation, which was not only comparable but in some casesbetter—particularly for serum ALT and AST as well as hepaticlipid peroxidation, antioxidant enzymes, TNF-α, and IL-6.
Similarly, the rich polyphenol fractions of methanolicextracts of Genista quadrifloraMunby and Teucrium poliumgeyriiMaire showed a protective effect against hepatoxicity ofacetaminophen (APAP) and the comparison with N-acetyl-cysteine showed their comparable properties with the drug,except for histological changes where Teucrium polium geyriiMaire exerted a better influence than two other studiedagents [20].
3.4. The Comparison of Plant Extracts with Silymarin, anAcknowledged Dietary Supplement of HepatoprotectiveProperties. Many drugs and chemicals are distinguished by
their hepatoxic effects. In view of the increasing environmen-tal pollution as well as more and more common applicationof different drugs, often over-the-counter ones, the protectiveagents are highly desirable [18]. Silymarin, a preparationobtained from Silybum marianum L., has been used as ahepatoprotective adjuvant for years. Currently, the attentionhas been pointed to other plants, often those used sinceantiquity in traditional medicine [44]. Different hepatotoxic-ity animal models were used to perform comparison withsilymarin.
The possibility of replacing silymarin by an extract ofCassia fistula L. leaves was studied by Kaur et al. [35] in ratsexposed to thioacetamide. The studied extract was applied atthree doses (50, 100, and 200mg/kg b.w.), and beneficialeffects of the two higher ones were not worse than thoseobserved in rats receiving silymarin.
The similar observations were reported by Fahmi et al.[53] who compared the protective properties of dietary gin-ger against diethylnitrosamine hepatotoxicity in rats withthose showed by silymarin and found that the studied mate-rial in the form of ginger powder or essential oil exerted thesame or even better beneficial action.
Choi et al. [46] studied the possibility of Centella asiaticaleaf ethanol extract (100 or 200mg/kg) using as a protectiveagent against dimethylnitrosamine-induced hepatotoxicityin rats. The authors determined different inflammatory cyto-kines and mediators, liver injury markers, oxidant parame-ters, and histophological changes. In some cases (liverhistology, serum IL-1β, TNF-α, and IL-2), both doses of theextract showed a better action than silymarin. In case ofAST, ALP, IL-6, and INF-γ or liver MDA, both agents dis-played the similarly significant properties. Furthermore, liverantioxidant enzymes were best ameliorated by the higherdose of plant preparation.
El-Hadary and Ramadan [52] in turn stated thatMoringaoleifera leaf extract displayed protective properties againsthepatotoxic action of diclofenac sodium. The comparisonwith silymarin proved that the plant preparation exertedcomparable or even better effect.
Ahmad and Zeb [18] in turn compared an effectiveness ofsilymarin and different doses of water extract of Trifoliumrepens leaves against acetaminophen-induced hepatoxicityin mice. The authors reported that in case of most studiedhematological, serum biochemical, and liver oxidativeparameters, the effect of the highest dose was not worse thanthat shown by silymarin.
However, the comparison of protective action of leafextract of Solanum surattense with that observed for sily-marin in CCl4-exposed rats revealed that the latter hadentirely better effect regarding liver injury markers and lipidprofile in serum as well as lipid peroxidation process in theliver [83].
On the other hand, Dogan and Anuk [44] observedthat in ethanol-exposed rats water extract of leaves ofPlatantus orientalis L. generally showed the protectiveeffects comparable or even better than those observed insilymarin-given animals. Interestingly, in case of someparameters, both silymarin and extracts showed insuffi-cient effectiveness.
43Oxidative Medicine and Cellular Longevity
The possibility of applying a plant extract as an adjuvantwhich could augment an action of an acknowledged agentwas also studied on an example of silymarin. Azim et al.[19] investigated effects of silymarin alone, Moringa pere-grina leaf extract alone, and coadministration of those sub-stances in rats subjected to acetaminophen. Generally, asregards plasma liver injury markers and oxidative parame-ters, the protective influence of all three treatments wasfound to be practically complete, but in some cases, the com-bination of both agents exerted the best effect. Interestingly,DNA damage was most markedly alleviated by plant extractalone while silymarin showed the slightest efficacy.
3.5. Immunosuppressive and Anti-Inflammatory Drugs vs.Plant Preparations. Pistacia weinmannifolia root extractwas compared regarding anti-inflammatory effects withroflumilast—a drug used in the therapy of lung inflammatorydisorders, in mice with pulmonary inflammation induced bycigarette smoke and lipopolysaccharide. The results of theexperiment showed that the studied preparation possessedprotective properties absolutely comparable with the appliedmedicine [149].
Sundaram et al. [55] studied the protective effect of gug-gulipid (an extract from Commiphora whighitii gum resin)against morphology changes, cartilage degradation, and pro-oxidative processes in rats with experimental arthritis. Alongwith the evaluation of the plant preparation properties, theauthors performed the comparison with a standard nonste-roidal anti-inflammatory drug ibuprofen. The influence ofthe studied extract proved to be comparable or even muchmore effective, particularly in cases of hematological andoxidative parameters.
In a study performed on mice subjected to 1-chloro-2,4-dinitrobenzene with the aim of inducing atopic dermatitis-like skin lesion, the effect of Rumex japonicus Houtt. rootextract was compared with the efficacy of a synthetic gluco-corticoid dexamethasone. The alleviation of the diseaseseverity caused by the topical application of the plant extractwas not much worse (particularly in the case of the higherdose) than that observed in animals treated intraperitoneallywith dexamethasone [77].
Kaveh et al. [117] in turn compared the influence of dif-ferent doses of hydroethanolic extract of Portulaca oleraceawith that exerted by dexamethasone in rats with experimen-tal asthma. According the authors, the effect of the highestdose (4mg/mL in drinking water) was comparable with thedrug. However, the lowest dose (1mg/mL in drinking water)in some cases showed no beneficial influence.
In some cases, the pharmaceutical agents showed a bettereffect. Sdayria et al. [41] reported that in mice withcarrageenan-induced paw edema pretreatment with a non-steroidal anti-inflammatory drug indomethacin or Euphor-bia retusa methanol extract showed comparable effectsconcerning % edema inhibition, although indomethacin dis-played a little better properties. However, in case of oxidantparameters in the liver and paw, the drug exerted more dis-tinct beneficial influence.
In the experiment performed by Jeong et al. [48], a non-steroidal anti-inflammatory drug celecoxib proved to be
much better in reversing the changes of biochemical param-eters observed in rats with monosodium iodoacetate-inducedosteoarthritis than a water extract of leaves of Morus alba L.Histological examinations confirmed the drug advantage.
3.6. Standard Drugs vs. Plant Preparations in Stomach UlcerAnimal Model. Sattar et al. [137] performed a comparisonof protective action of Myristica fragrans extract and sucral-fate (a drug used for stomach ulcer treatment) in rats withethanol-induced gastric ulcers. Although the plant prepara-tion was not so effective with regard to amelioration of totalacidity of stomach contents as well as macroscopic evaluationof gastric mucosa, ulcer index, and percentage of protection,its application did not cause serious increase in pH of stom-ach content as sulfacrate (4.25 vs. 5.0).
On the other hand, Biebersteinia multifida hydrometha-nolic extract showed a quite comparable or better protectiveeffect than another drug—namely, omeprazole—in cases ofgastric ulcers caused by 75% ethanol in rats. This effectincluded a decrease in ulcer area and number as well asenhancement of total antioxidant capacity in gastricmucosa [134].
Ateufack et al. [150] compared the effect of Piptadenias-trum africanum stem bark aqueous and methanol extracts(125, 250, or 500mg/kg) in rat gastric ulcer induced by theHCl/ethanol mixture, indomethacin, and acetic acid withthat showed by standard drugs (Maalox, Misoprostol, orRanitidine). Plant extracts, particularly aqueous one whenapplied in the highest dose, displayed the protective actioneven better than the investigated drugs in case of animalsexposed to HCl/ethanol mixture or indomethacin, but notin those treated with acetic acid.
Rtibi et al. [135] reported that in rats exposed to ethanol,pretreatment with Ceratonia siliqua L. aqueous extract (500,1000, and 2000mg/kg b.w.) showed a better or comparableeffect with the standard drug famotidine when applied atthe highest dose, while the lowest one was found to be eitherless effective or even ineffective at all.
The interesting results were reported by Chanda et al.[45]. The scientists studied the possibility of using Paederiafoetida Linn. leaf methanol extract (100 and 200mg/kgb.w.) as a gastroprotective agent in rats with gastric ulcersinduced by indomethacin-pylorus ligation, alcohol, or waterimmersion stress. The effects were compared with thoseobtained for standard drugs ranitidine, sucralfate, and lanso-prazole, respectively. As concerns ulcer protection, in the firstand third models, there were no distinct differences betweenthe plant material (particularly the higher dose) and theapplied drug. In contrast, in the second model, the higherdose of extract showed much better effectiveness than thelower one, but nonetheless not so high as sucralfate.
3.7. The Comparison of Plant Preparations withCytoprotective Adjuvants Used in Radio and Chemotherapy.The advantage of plant origin substances over drugs was alsoshown by Dong et al. [70]. Ethanol extract of JXT (a tradi-tional herb obtained from the Spatholobus suberectus Dunndry rattan) given orally to mice caused a significant improve-ment of the biochemical parameters previously disturbed by
44 Oxidative Medicine and Cellular Longevity
60Co γ-radiation, i.e., morphology, bone marrow cell num-ber, and liver lipid peroxidation level as well as activity ofantioxidant enzymes. This effect was comparable or betterthan that exerted by amifostine, an agent applied in cases ofradiation syndrome during radiotherapy.
3.8. Plant Preparations vs. Drugs and Supplements Applied inNeurological and Psychiatric Disorders. Pharmaceuticalagents used for the treatment of psychiatric and neurodegen-erative disorders may cause side effects worsening the condi-tion of patients. Plant preparations, often used for centuriesin traditional medicine, have been found to possess anxiolyticand antistress properties, and the comparison with acknowl-edged drugs and supplements showed their comparable effi-cacy [17, 58].
Plant materials, namely, extracts from two Hypericumspecies, were studied with regard to their effect on oxidativestress and inflammatory cytokines in an experimental anxi-ety animal model. The comparison with pure quercetin anda control drug alprazolam was also performed. In most cases,the disturbed brain parameters were positively influenced ina comparable or more distinct way by plant materials than bytwo other studied substances. It should be emphasized that insome cases the worst effect was observed in animals treatedwith alprazolam [17].
Almeida et al. [58] compared the protective effect ofClitoria ternatea extract with that shown by cotreatment withdietary supplements choline and docosahexanoic acidagainst brain oxidative stress caused by separation frommothers in rat pups. During 30-day experiment includingthe stressing factor and treatments as well as during the sub-sequent 330-day follow-up, both agents revealed comparableproperties regarding the prevention of lipid peroxidationincrease and thiol group content depletion.
Chonpathompikunlert et al. [31] compared the neuro-protective effect of Apium graveolens L. extract with thatshowed by a standard drug Tidomet Plus in an animal modelof Parkinson disease. The efficacy of two doses (250 and375mg/kg b.w.) proved to be quite comparable (the lowerone) or even better (the higher one) with the medicine asregards improvement of behavioral performance, oxidativeparameters, and activities of monoamine oxidases A and B.
3.9. Antidiabetic Drugs vs. Plant Preparations. The possibilityof plant preparations application in diabetic subjects was alsostudied. It was prompted by side effects occurring in patientstreated by pharmacological agents. The outcomes seem to bepromising although in view of the reported results the accu-rate research is needed to determine mechanism of actionand the most beneficial dose [66, 127].
Khanra et al. [129] stated that Abroma augusta L. leafmethanol extract (100 or 200mg/kg) was not so efficient atreversing the serum parameters disturbed in rats by type 2diabetes course, particularly in the case of the lower dose, asa standard drug glibenclamide. However, in the case of allevi-ating DNA fragmentation, ATP level, chosen oxidant param-eters, and expression of NF-κB in the kidney and heart, theprevalence of the drug was not so distinct.
The comparison of glibenclamide and methanolic extractof Caralluma europaea was performed by Dra et al. [127] ondiabetic mice. The higher dose of plant material (500mg/kgb.w.) was better effective in the reduction of blood glucosethan a drug, beginning from the 4th hour after administra-tion, while a lower one (250mg/kg b.w.) showed a compara-ble effect. Additionally, according to the authors, the lowerdose showed a more distinct beneficial influence in case ofhistopathological damage observed in diabetic animals.
The similar results were obtained by Du et al. [66] whocompared the protective properties of a standard drug met-formin hydrochloride and different doses (100, 250, and500mg/kg) of polysaccharide separated from Lycium bar-barum in the rat model of diabetes induced by high-fat diet+streptozotocin. Metformin showed a better effect in caseof fasting blood glucose and INF-α. As for insulin andICAM-1, the highest dose of plant origin material proved topossess better ameliorating properties, while serum GPxwas more improved by two higher doses.
Balbaa et al. [57] investigated the differences in effectsof administration of Nigella sativa seeds oil, standarddrugs metformin and glimepiride, and their combinationsto diabetic rats. The oil had a better protective actionwhen administrated alone than in combination withmetformin or glimepiride against oxidative stress and neu-roinflammatory cytokines’ increase. When the results ofadministration of those three agents alone to diabetic ratswere compared, the best properties of a plant materialwere also confirmed.
3.10. Plant Extract or a Single Substance of AntioxidantProperties? As beneficial effects of plant preparations wereattributed to their antioxidative properties, some researchesperformed the comparisons with simple substances ofacknowledged antioxidant character. The results showed thatplant materials could exert a better influence due to the pres-ence of many component which might cooperate with oneanother.
Jahan et al. [72] studied the possibility of application ofChenopodium album Linn. seed extract as a protective agentagainst the damage of reproductive functions caused by mer-cury exposure. They compared the effect of the plant extractwith that showed by a known antioxidant vitamin C whichwas reported to exert beneficial influence on male fertility.Except for plasma cholesterol and triglycerides as well asGST and TBARS in testicular tissue, the benefit influence ofthe studied plant material was comparable or even better.The similar observations were reported as regards the testic-ular morphometric parameters.
The comparison of the protective influence of Nigellasativa extract and vitamin E against cisplatin nephrotoxicitywas performed by Hosseinian et al. [16]. The cisplatin-induced negative changes, i.e., renal damage and thiol groupdecrease, and lipid peroxidation enhancement in the serumand kidney, were alleviated in a rather comparable way,except for serum thiols, where the prevalence of plant extractwas indisputable.
The effects of two Hypericum (H. maculatum and H.perforatum) species extracts on oxidative stress and
45Oxidative Medicine and Cellular Longevity
inflammatory cytokines were studied in an experimentalanxiety animal model and compared with pure quercetin.The beneficial influence of plant extracts was mostly compa-rable and in many cases better, particularly in the case ofHypericum maculatum [17]. Such results could point to syn-ergistic action of various components of extracts, acting asconfirmation of the conclusions made by He et al. [148].
3.11. The Action of a Plant Preparation Depending on ItsDose, Time and Form of Treatment
3.11.1. The Relationships between the Dose and the Effects. Inmany studies, the protective effects of plant extracts and con-stituents showed a direct dependency on the used dose [15,29, 31, 56, 80, 107, 117].
However, sometimes, the similar effects were observedfor a considerable wide range of the applied doses. Liu et al.[91] studied an effect of various doses (0.0625, 0.125, 0.25,0.5 g/kg b.w.) of ginseng oligopeptides against ethanol toxic-ity, and the observed differences were quite slight consideringthe size of the applied range.
Malik et al. [39] performed a study on animals with Hun-tington’s disease like symptoms and observed practically thesame influence of two different doses (100 and 200mg/kg) ofCelastrus paniculatus seed ethanol extract on memory func-tions, locomotor activity, and oxidative parameters in thebrain parts.
The relationships between used doses and an exertedinfluence were also studied in the experiment concerningthe protective properties of water extract of Sonneratia ape-tala fruit against liver damage caused by acetaminophenexposure in mice. The effects of pretreatment with differentdoses (100, 200 and 400mg/kg) were very interesting as inthe case of some parameters a strong dose dependency wasobserved (e.g., liver GSH and MDA), while some other oneswere affected in the same way, regardless of the applied dose(liver GSH, T-AOC, and TNF-α) [51].
In another study, Wang et al. [119] investigated the pro-tective properties of two doses (4.6 or 14 g/kg b.w.) of aque-ous extract of Salvia Miltiorrhiza Bge. f. alba in themonocrotaline-induced animal model of pulmonary hyper-tension. Various parameters were studied: mean pulmonaryartery pressure, right ventricular systolic pressure, pulmo-nary artery remodelling, plasma vasoactive factors NO, 6-Keto-PGF1α, ET-1, and TXB2, and lung TGF-β1, but theobserved differences were not as considerable as one couldexpect taking into account the difference between the applieddoses.
The similar observations were reported by El-Hadary andRamadan [52] who studied two doses ofMoringa oleifera leafextract (150 and 300mg/kg b.w.) against hepatotoxicity ofdiclofenac sodium. Both doses displayed protective proper-ties, but again, the difference between them was not so greatas one could predict considering their range.
Onyenibe et al. [122] studied the efficacy of two doses ofMonodora myristica aqueous extract at preventing impair-ment of lipid profile and oxidative parameters in hypercho-lesterolemic rats and generally found no difference between100mg/kg b.w. and 200mg/kg b.w.
Such results point to the necessity of complex research ofany possible protective agent with using a wide range ofdoses. The issue of dependency between the used dose andits effects proved to be additionally complicated as not alwaysa direct relationship was found. The effects of different doseswere sometimes divergent as in the experiment performed byKhan et al. [88], who studied the influence of two doses0.5 g/kg b.w. and 1.0 g/kg b.w. of ajwa dates (Phoenixdactylifera L.) water extract on the biochemical parametersin rats with diethylnitrosamine-induced liver cancer. Thelower one in some cases showed even a harmful effect (poten-tializing the changes caused by the carcinogen), while thehigher one showed considerable protective properties. Addi-tionally, the lower dose effect was characterized by a signifi-cant diversity as apart from showing the above-mentionedharmful influence, it also exerted a beneficial action, rangingfrom slight to strong.
In some cases, the higher dose had the worse effect than alower one. In the study performed by Omole et al. [26], con-cerning the possible use of pretreatment with kolaviron (amixture of flavonoids obtained from Garcinia kola seeds,200 or 400mg/kg/d) against toxicity of cyclophosphamide,the higher dose proved to be less beneficial, not only exertingless protective properties but also causing a slight increase inlipid peroxidation in the heart tissue.
The similar observations were reported by Apaydin Yil-dirim et al. [28] who studied the influence ofHelichrysum pli-catum DC. subsp. plicatum extract (100 or 200mg/(kg·d)against nephrotoxic as well as hepatotoxic effects of gentami-cin in rats. The authors stated that the higher dose showedmuch less beneficial influence. Additionally, the higher doseexerted some harmful effects, particularly regarding histopa-hological changes, when administered alone.
In some studies, it would be really very difficult to decidewhich dose should be chosen for usage. In the experimentperformed by Wattanathorn et al. [42], the beneficial influ-ence of the combination of extracts of Mangifera indica L.and Polygonum odoratum L. against diabetes cataract andretinopathy was distinctly showed, but the effect of differentdoses (2, 10, or 50mg/kg b.w.) was found to be highly diverse.
Phunchago et al. [92] studied the possible protectiveeffect of Tiliacora triandra water extract against ethanol-induced hippocampus damage in rats. The authors com-pared three doses: 100, 200, and 400mg/kg b.w., and foundthat the middle one showed the best influence in improvingsome studied parameters while in few cases the worst influ-ence was found for the highest one.
3.11.2. The Relationships between the Period of Treatmentand the Effects. The period of the treatment with the studiedsubstances also proved to be a factor of importance. Xu et al.[60] investigated the effect of Rhubarb extract on the oxida-tive parameters in rats with traumatic brain injury. Accord-ing to the reported results, the degree of improvement inlipid peroxidation intensity as well as antioxidants levelsshowed a dependency on the time of experiment. The ani-mals sacrificed after a longer period, starting from surgeryand plant material treatment, showed a better ameliorationof the studied parameters.
46 Oxidative Medicine and Cellular Longevity
3.11.3. The Relationships between the Way of Preparing PlantMaterials and Their Effects. As plant extracts contain manyactive substances of different solubilities in various solvents,the way of the preparation of the used substances also provedto be an issue of importance.
Malik et al. [39] studied the fractions of Celastruspaniculatus seed ethanol extract, obtained by suspendingit in water and sequential partitioning with using petro-leum ether, ethyl acetate and n-butanol. These materialswere investigated as to their ability to ameliorate the neu-rotoxic effect of 3-nitropropionic acid by reversing changesof oxidative parameters in striatum and cortex of experi-mental rats. In the case of improvement of enhancedMDA and nitrites as well as decreased CAT, SOD, andGSH, ethanol extract and aqueous fraction proved to bethe most effective; the petroleum ether fraction showedmuch less efficacy while n-butanol and ethyl acetate onespractically none.
3.11.4. Treatment of Pretreatment? The way of treatment, i.e.,pre or post, in some cases was shown to be a crucial factorinfluencing the observed effect to a considerable degree.Afsar et al. [23] studied the effects of ethyl acetate fractionof Acacia hydaspica methanol extract against cisplatin toxic-ity and observed that the protective influence observed in thecase of posttreatment started concomitantly with cisplatinand continued for five days was decidedly less distinct thanthat of 15-day pretreatment combined with posttreatment.
On the other hand, some authors did not report anydifferences between the mentioned two ways. Khattab et al.[146] did not observe any differences between pre- and post-treatment with Borago officinal L. seed oil in rats exposed toγ-radiation.
The similar effects were observed by Nasri et al. [109]in rats subjected to a contrast medium iodixanol and 70%ethanol green tea extract. The plant agent alleviatediodixanol-induced histopathological kidney changes, butno significant differences between pre- and posttreatmentwere observed.
Hosseinian et al. [16] studied the possible protectiveeffect against cisplatin nephrotoxicity ofNigella sativa extract(100 and 200mg/kg) using the design, whereby two ways ofadministration were applied—pretreatment alone or withthe addition of posttreatment. The outcomes were reallyinteresting. In case of renal SH groups and tissue damage aswell as serum SH groups and MDA plant material provedto possess beneficial effect, regardless of the way ofadministration.
4. The Effects of Plant Preparations Per Se
The fact that generally effects of plant preparations per sewere observed occasionally makes the considerable limitationof the studies presented in the current review. Only a few sci-entists reported observations considering any influence of thestudied materials. Sheweita et al., for instance, investigatedthe effects of application of essential oils of Foeniculumvulgare (fennel) Miller seeds, Cuminum cyminum L. (cumin)seeds, and Syzygium aromaticum L. (clove) flower and
reported that the used oils themselves caused several benefi-cial effects like decrease in liver TBARS as well as enhance-ment of liver antioxidants [101].
El-Kashlan et al. [143] found the decrease in lipid perox-idation as well as reinforcement of antioxidant defence in ratsreceiving commercial date palm pollen.
El-Rahman et al. [110] reported alleviation of prooxida-tive processes as well as the increase in antioxidants in ratsgiven Saussurea lappa root extract.
Furthermore, the beneficial influence of plant prepara-tions included not only improvement in biochemical param-eters. Sheng et al. [33] reported that, apart from positiveeffect on body and adipose tissue weight and insulin sensitiv-ity, liver, and kidney functions, addition of mulberry leavespowder to diet also caused amelioration of microbiota com-munity structure in gut of obese mice.
Balbaa et al. [57] investigated the differences in theeffects of administration of Nigella sativa seeds oil, antidia-betic drugs metformin and glimepiride, and their combina-tions to rats. In some cases, the plant oil per se showed theleast or no negative effect in nondiabetic rats when com-pared to medicines. The reduction of brain β-amyloid-42as well as the increase in antioxidants’ level was observed.On the other hand, brain lipid peroxidation was found tobe enhanced.
However, some authors reported the negative effects ofplant preparations on experimental animal organisms.
Apaydin Yildirim et al. [28] observed histopathologicalchanges in organs of animals treated with Helichrysum plica-tum DC. subsp. plicatum extract.
In one of the recently published articles, Nahdi et al.[151] observed that leaf Hypericum humifusum aqueous(200 or 400mg/kg b.w.) and methanolic (10 or 20mg/kgb.w.) extracts, given to rats, induced histopathologicalchanges as well as impaired biochemical parameters includ-ing an increase in WBC, liver MDA, plasma ALT, AST, andLDH. Additionally, activities of hepatic antioxidant enzymesCAT and SOD were markedly decreased vs. control with notreatment. Interestingly, in case of the aqueous extract, theworse effect was exerted by the lower dose while the metha-nolic one was found to be more harmful when given in thehigher dose.
5. Conclusions
The outcomes of the studies presented in the currentreview showed a huge potential inherent in plant prepara-tions. They were revealed to reverse or alleviate toxicity ofdifferent factors, side effects of drugs, and symptoms ofvarious diseases. In many cases, they were proved to becomparable or better than standard drugs which let us sug-gest that in future the plant origin substances could make areplacement for pharmaceutical agents. However, the pre-sented above results of some experiments point to the factthat the proper precautions must be undertaken beforeapplying any plant material. The detailed research regard-ing the per se effects, dose, and way of administrationneeds to be performed.
47Oxidative Medicine and Cellular Longevity
Abbreviations
AA: Ascorbic acidAβ: β-Amyloid peptideABCG: ATP-biding cassette, subfamily G
transportersACC: Acetyl-CoA carboxylaseAChE: Acetylcholine esteraseACP: Acid phosphataseADA: Adenosine deaminase activityAGE: Advanced glycation end productAGGRECAN: Cartilage-specific proteoglycan core proteinALB: AlbuminAlCl3: Aluminium chlorideALP: Alkaline phosphataseALT: Alanine aminotransferaseAOPP: Advanced oxidation protein productsAR: Aldose reductaseARE: Antioxidant-responsive elementAST: Aspartate aminotransferaseATP: Adenosine triphosphateBALF: Bronchoalveolar lavage fluidBAP: Biological antioxidant powerBAT: Brown adipose tissueBcl-2: B-cell lymphoma 2BMP2: Bone morphogenetic protein 2BUN: Blood urea nitrogenb.w.: Body weightCa: CalciumCa2+ATPase: Calcium-activated adenosine 5′
-triphosphataseCAT: CatalaseCCl4: Tetrachlorometan (carbon tetrachloride)Cd: CadmiumCd36: Cluster of differentiation 36cGMP: Cyclic guanosine-3′,5′-monophosphateChAT: Choline acetyltransferaseCHOP: C/EBP homologous proteinCK-MB: Creatinine kinase-MBCOL2: Collagen type-IICOL10: Collagen type 10COMP: Cartilage oligomeric matrix proteinCOX-2: Cyclooxygenase-2CR: CreatinineCRP: C-reactive proteinCS: Citrate synthasecTnI: Cardiac troponin ICTX-II: C-telopeptide of type II collagenCu: CopperCYP2E1: Cytochrome P450-2E1DBP: Diastolic blood pressureDC: Diene conjugateDHEAs: Dehydroepiandrosterone sulfateDNA: Deoxyribonucleic acidE2: EstradioleNOS: Endothelial nitric oxide synthaseERK1/2: Extracellular signal-regulated kinase 1 and 2ET-1: Endothelin-1
Fatp4: Fatty acid transport protein 4Fe: IronFFA: Free fatty acidsFRAP: Ferric reducing ability of plasmaFSH: Follicle-stimulating hormonefT3: Free T3fT4: Free T4γ-GCS: γ-Glutamyl cysteine synthetaseGGT: γ-Glutamyl transferaseGM-CSF: Granulocyte-macrophage colony-
stimulating factorG6PD: Glucose-6-phosphate dehydrogenaseGPx: Glutathione peroxidaseGR: Glutathione reductaseGRP78: 78 kDa glucose-regulated proteinGSH: Reduced glutathioneGSSG: The oxidized form of glutathioneGSSG-red: Oxidized glutathione reductaseGSSP: Glutationylated proteinsGST: Glutathione-S-transferaseHA: HyaluronidaseHbA1c: Glycated hemoglobinHCT: HaematocritHDL: High-density lipoproteinHDL-c: High-density lipoprotein cholesterolHg: MercuryHGB: HaemoglobinHMG-CoA-R: 3-Hydroxy-3-methylglutaryl CoA
reductaseHNE: 4-Hydroxy-2-nonenalHO-1: Heme oxygenase 1H2O2: Hydrogen peroxideHOMA-IR: Homeostasis model assessment-insulin
resistanceICAM-1: Intercellular adhesion moleculei.c.v.: IntracerebroventricularIDE: Insulin degradation enzymeIFN-α: Interferon-αIFN-γ: Interferon-γi.g.: IntragastricallyIgG: Immunoglobulina GIgM: Immunoglobulina MIL: Interleukini.m.: IntramuscularlyiNOS: Inducible nitric oxide synthasei.p.: Intraperitoneallyi.v.: IntravenouslyJAK: Janus kinaseK: PotassiumKEAP1: Kelch-like ECH-associated protein 16-Keto-PGF1α: 6-Keto-prostaglandin F1 alphaLDH: Lactate dehydrogenaseLDL: Low-density lipoproteinLDL-c: Low-density lipoprotein cholesterolLH: Luteinizing hormoneLpl: Lipoprotein lipaseLPO: Lipid peroxidationLPS: Lipopolysaccharide
48 Oxidative Medicine and Cellular Longevity
MAO-A: Monoamine oxidase type BMAO-B: Monoamine oxidase type BMCP-1: Monocyte chemoattractant protein 1M-CSF: Macrophage colony-stimulating factorMDA: MalondialdehydeMDSCs: Myeloid suppressor cellsMg: MagnesiumMg2+ATPase: Magnesium-activated adenosine 5′
-triphosphataseMIP: Macrophage inflammatory proteinMMP-1: Matrix metalloproteinase-1, interstitial
collagenaseMMP-3: Matrix metalloproteinase-3, stromelysin-1MMP-13: Matrix metalloproteinase-13, collagenase 3MMP: Matrix metalloproteinaseMPO: MyeloperoxidasemRNA: Messenger ribonucleic acidMT: MetallothioneinMTH 1: A gene encoding 8-oxo-7,8-dihydrodeoxy-
guanosine triphosphataseNa: SodiumNADH: Nicotinamide adenine dinucleotide
reduced formNa+/K+ATPase: Sodium- and potassium-activated adeno-
sine 5′-triphosphataseNASH: Nonalcoholic steatohepatitisNF-κB: Nuclear factor-kappa BNO: Nitric oxideNO3: NitrateNO2: NitriteNOX: NADPH oxidaseNP-SH: Nonprotein sulfhydryl groupsNQO1: NAD(P)H:quinone oxidoreductase 1Nrf2: Nuclear erythroid 2-related factor 28-OHdG: 8-Hydroxy-2′deoxyguanosineOSI: Oxidative stress indexP: PhosphorusP53: p53 proteinpACC: Phosphorylated acetyl-CoA carboxylasepAMPK: Phosphorilated adenosine-
monophosphate-activated protein kinasePb: LeadPC: Protein carbonylsPCG: Protein carbonyl groupsPCNA: Proliferating cell nuclear antigenpeNOS: Phosphorylated eNOSPGE2: Prostaglandin E2PGI2: ProstacyclinPHGPx: Phospholipid hydroxyperoxide GPxPKC: Protein kinase CPLT: PlateletsP38 MAPK: p38 mitogen-activated protein kinasepNF-κB: Phospho-NF-κBp.o.: OrallyQR: Quinone reductaseRANTES: Regulated on Activation, Normal T-cell
Expressed and SecretedRBC: Red blood cells
ROS: Reactive oxygen speciesSBP: Systolic blood pressures.c.: SubcutaneouslySDH: Sorbitol dehydrogenaseSH: Thiol groupsSHBG: Sex hormone-binding globulinSOD: Superoxide dismutaseSPF: Specific pathogen freeSrebf1: Sterol regulatory element-binding tran-
scription factor 1SREBP-1c: Sterol-regulatory-element binding protein-
1cSTAT: Signal transducer and activator of
transcriptionT: TestosteroneT-AOC: Total antioxidant capacityTAS: Total antioxidant statusTBARS: Thiobarbituric acid reactive substancesTC: Total cholesterolTG: TriglyceridesTGF-β: Transforming growth factor betatHcy: Total homocysteineTIMP: Tissue inhibitor of metalloproteinasesTLC: Total leukocytic countTLR: Tall-like receptorTNF-α: Tumor necrosis factor alphaTOS: Total oxidant statusTP: Total proteinTSH: Thyroid-stimulating hormoneTXA2: Thromboxane A2TXB2: Thromboxane B2UA: Uric acidUDPGT: UDP-glucuronosyl transferaseVEGF: Vascular endothelial growth factorVLDL: Very low-density lipoproteinVLDL-c: Very low-density lipoprotein cholesterolWBC: White blood cellsXO: Xanthine oxidaseZn: Zinc.
Conflicts of Interest
The authors declare that there is no conflict of interestregarding the publication of this article.
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