garlic & health health part university of leipzig
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Garlic & Health
Health Part
University of Leipzig
Garlic & Health: Health part - general aim
University of Leipzig
Main Goal: - Interactive improvement of garlic quality
Elucidation of mechanismAnalysis of active of actioncompounds Improved drug
formulationHigh quality garlic
Improvement of garlic Optimal use of garlicplants and growth conditions for therapeutic application
Main Focus: - Inflammation and cytokine signaling- Atherosclerosis and serum cholesterol - Cancer and biotransformation
- Human Intervention Study
Garlic & Health: WP5 Cholesterol and cytokines
University of Leipzig
Acetyl-CoA
HMG-CoA
Mevalonate
Squalene Lanosterol CHOLESTEROL
HMG-CoA-
Reduktase
inactivatingmechanisms
Garlic-Extract Allicin
Metabolites
Gastrointestinal- Tract
High Quality Garlic:
Inhibition of cholesterol biosynthesis
Indirect Mechanism of Inhibition:
Aim: Interaction of garlic constituents with cholesterol biosynthesis
Garlic & Health: WP5 Cholesterol and cytokines
University of Leipzig
Challenge for future project research:
Plant part: Health part:Definition of growth conditions Analysis of responsibel compoundsFertilisation Elucidation of mechanism of action(Genetic) Modification of plants Implications for human health
UnexpectedResult !!
Low Quality Garlic:
Stimulation of cholesterol biosynthesis !
Garlic & Health: WP5 Cholesterol and cytokines
University of Leipzig
Aim: Interaction of garlic constitutents with vessel wall
0,0 1 5 10 50 100 5000
20
40
60
80
100
120
140
DADS AM SAC
Ab
sorb
an
ce (
%)
Concentration (µM)
Inhibition of Matrix Metalloproteinase-2 Production by DADS, AM and SAC in HCA-endothelial cells
No influence on adhesion moleculesand NF-kB activity
Garlic & Health: WP5 Cholesterol and cytokines
University of Leipzig
Aim: Interaction of garlic constitutents with cytokine production in human blood
• Garlic extracts influence the liberation of pro- and antiinflammatory cytokines in human blood
• High quality garlic shows a better biological cytokine profile
• Cytokine modulation may indirectly affect NF-kB activation
Garlic & Health: WP6 Cancer and biotransformation
University of Leipzig
Aim: Bioavailability of garlic constituents
-0,1
0
0,1
0,2
0,3
0,4
0,5
0 5 10 15 20 25hours
com
poun
d (µ
g/g
liver
)
DADS
AM/10
AMS/100
AMSO/100
AMSO2/100
DADS
S
S
O
S
S
DADSO
In vivo
AGS
SH
S
AMAMS
AMSO2
S
O
AMSO
Sglutathione
In vitro
Garlic & Health: WP6 Cancer and biotransformation
University of Leipzig
Aim: Protection againstgenotoxicity by garlic constituents
% o
f D
NA
alte
ratio
ns
0
20
40
60
80
100
120
H202 5 µM 25 µM 50 µM 100µM
Effects of S-allylcystein on H2O2 genotoxicity in HepG2 cells
Effects of garlic powders on hepatic UGT activity in rat consuming garlic powders
C S0 S50 S100 S200 D
Act
ivity
(n
mo
les/
min
/mg
pro
tein
)
0
10
20
30
40
UGT
**
*
Aim: Modulation of enzymes of carcinogenactivation or detoxification
0 50 100 200 Fertilization
Garlic & Health: WP7 Pharmaceutics
University of Leipzig
Aim: - Development of reliable analytical methods- Development of improved pharmaceutical formulation
0 10 20 30 40 50 60min
1 234
5
6
7
1 Alliin2 g-Glutamyl-S-allylcysteine3 g-Glutamyl-S-trans-1-propenylcysteine4 g-Glutamyl phenylalanine5 Allicin6 Dithiines7 Sulfides
0
0,5
1
1,5
2
2,5
3
AU
T 1
AU
T 2
GE
R 1
ITA
1
ITA
2
NL
1
NL
2
SW
E 1
SW
E 2
SW
E 3
UK
1
Co
nte
nt
[%]
Alliin
Allicin
Peptides
„All purpose“ HPLC method Comparison European Market Products
Garlic & Health: WP8 Human Intervention Study
University of Leipzig
Aim: Placebo-controlled study
Run-in period Intervention period6 13 19 weeks
Blood and urine collection
Healthy volunteers with increased risk
(mildly hyercholesterolemic)
Surrogate markers of atherosclerosis:
Plasma lipids (cholesterol, triglycerides, HDL, LDL, lp(a))
Von Willebrand factor
Adhesion molecules (VCAM-1, ICAM-1, E-selectine)
Surrogate markers of cancer:
Phase II enzymes
DNA damage