review article fucoxanthin: a promising ... - hindawi

Review ArticleFucoxanthin A Promising Medicinal and Nutritional Ingredient

Hui Zhang1 Yibo Tang2 Ying Zhang3 Shuofeng Zhang4 Jing Qu2 Xu Wang2

Ran Kong4 Chunchao Han1 and Zhenquan Liu2

1School of Pharmacy Shandong University of Traditional Chinese Medicine Jinan 250355 China2School of Basic Medical Sciences Beijing University of Chinese Medicine Beijing 100029 China3Department of Dermatology The First Hospital of Chinese Peoplersquos Liberation Army Gansu 730030 China4School of Chinese Materia Medica Beijing University of Chinese Medicine Beijing 100029 China

Correspondence should be addressed to Chunchao Han chunchaoh126com and Zhenquan Liu liuzhenquan10804126com

Received 4 January 2015 Accepted 4 May 2015

Academic Editor Avni Sali

Copyright copy 2015 Hui Zhang et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Fucoxanthin an allenic carotenoid can be isolated from edible brown seaweeds Recent studies have reported that fucoxanthin hasmany physiological functions and biological properties such as antiobesity antitumor antidiabetes antioxidant anti-inflammatoryand hepatoprotective activities as well as cardiovascular and cerebrovascular protective effects Therefore fucoxanthin can beused as both medicinal and nutritional ingredient to prevent and treat chronic diseases Although fucoxanthin possesses manymedicinal ingredient and nutritional qualities studies indicated that its structure was unstable In this paper we consulted thecurrent documents and reviewed structural properties and factors affecting the stability of fucoxanthin We also reported themetabolism safety pharmacological activities and the methods of improving the bioavailability of fucoxanthin Based on thesestudies providing essential background knowledge fucoxanthin can be developed into marine drugs and nutritional products

1 Introduction

Recently the intake of fats sugars and calories is increasingwhereas exercise and physical activities are reduced Thislifestyle contributes to related diseases like obesity diabetesmellitus cancer and other chronic diseases To prevent andtreat lifestyle-related diseases it is not sufficient to use anexclusively pharmacological treatment Nutrition also playscritical roles [1] Therefore researchers begin to find safe andeffective functional ingredients in food to prevent and treatlifestyle-related diseases [2] One of these functional ingredi-ents is fucoxanthin

Fucoxanthin is a marine carotenoid and presents in themacroalgae and microalgae such as Undaria pinnatifida(Wakame) Laminaria japonica (Ma-Kombu) Phaeodacty-lum tricornutum and Cylindrotheca closterium [3]The struc-ture of fucoxanthin was determined by Englert et al [4]Fucoxanthin has a unique molecular structure (Figure 1)including an unusual allenic bond a 56-monoepoxide and 9conjugated double bounds [5 6]The allenic bondwasmainly

in fucoxanthin which was not found in other carotenoidsin brown seaweeds [7] However the unique structure andchirality of fucoxanthin are unstable It is easily affected byheating aerial exposure and illumination [8 9] Thoughfucoxanthin is unstable the factors contributing to its insta-bility has been thoroughly studied Because of its unstablestructure and the allenic bond fucoxanthin showed highantioxidant activity [10] Moreover fucoxanthin also showedantiobesity antidiabetes anti-inflammatory anticancer andhepatoprotective activities as well as cardiovascular andcerebrovascular protective effects [11ndash54] In this paper wereviewed the factors affecting the stability of fucoxanthin themetabolism and safety of fucoxanthin the pharmacologicalactivities and the pharmacological mechanism of fucoxan-thin

2 Structure of Fucoxanthin

The structure of fucoxanthin is closely related to pharmaco-logical activities of fucoxanthin Therefore properties of its

Hindawi Publishing CorporationEvidence-Based Complementary and Alternative MedicineVolume 2015 Article ID 723515 10 pageshttpdxdoiorg1011552015723515

2 Evidence-Based Complementary and Alternative Medicine

HO

O

O

OH

C

OCOCH3

Figure 1 The chemical structure of fucoxanthin

structure are necessary to be well known Fucoxanthin is acharacteristic carotenoid which was found in brown algaeStructure of fucoxanthin (Figure 1) is similar to neoxanthindinoxanthin and peridinin Unlike other carotenoids fucox-anthin has a unique structure in which an unusual allenicbond 9 conjugated double bounds a 56-monoepoxide andsome oxygenic functional groups including hydroxyl epoxycarbonyl and carboxyl moieties are present [55 56]

Like other carotenoids fucoxanthin was ready to bedegraded during storage as a result of exposure to heat lightoxygen enzymes unsaturated lipids and other prooxidantmolecules [55]The formation of some cis-isomers by isomer-ization would happen which was related to treatment condi-tions and medium and type of carotenoids [55ndash57] Purifiedfucoxanthin usually resulted in three main peaks consistingof the trans-form along with two isomers [58] The ratio ofcis-isomers of fucoxanthin was increased with the increaseof extraction temperature [58] Kawee-ai et al also foundthat when the ratio of cis-isomers increased the antioxidantactivities of fucoxanthin decreased [58] A spectrophotomet-ric analysis about fucoxanthin in canola oil was analyzed byZhao et al [9] The results showed that heating caused thedegradation of total and all-trans fucoxanthin between 25 and100∘C in the absence of light and air [9] With the increaseof heating temperature the formation of 13-cis and 131015840-cisand the degradation of 91015840-cis would also be promoted Andthe process was found to follow simple first-order kineticsZhao et al [9] also found the degradation of all-trans and13-cis and 131015840-cis fucoxanthin was synergistically promotedwhen exposed to both air and light [9]These studies providedessential background knowledge on the properties of fucox-anthin In the process of extracting purifying storing andusing of fucoxanthin the heating aerial exposure and illu-mination should be avoided as much as possible

3 Metabolism and Bioavailability ofFucoxanthin

The absorption and metabolism of fucoxanthin are closelyrelated to its bioavailability It is essential to know the meta-bolic process and the method to improve the bioavailabilityof fucoxanthin (Figure 2)

Fucoxanthinol and amarouciaxanthin A are the mainmetabolites of fucoxanthin Fucoxanthin seemed to be rap-idly hydrolyzed to fucoxanthinol in the gastrointestinal

tract within 2 h after the administration and no unchangedfucoxanthin was detected in the plasma or liver in mice[59] Fucoxanthinol was converted into amarouciaxanthin Awhich was predominantly shown in livermicrosomes ofmiceand in HepG2 cells [59] The study in vitro by Hashimotoet al [60] demonstrated that dietary fucoxanthin accumu-lated in the heart and liver as fucoxanthinol and in adiposetissue as amarouciaxanthin A

Yonekura et al [61] investigated the metabolism tissuedistribution and depletion of fucoxanthin in ICR miceThey found fucoxanthinol and amarouciaxanthin A in micepartitioned more into adipose tissues than into plasma liverand kidneyThe half-life of the depletion (11990512) of fucoxanthinmetabolites in adipose tissues (gt41 d) was longer than thatin plasma (116 d) liver (263 d) and kidneys (444 d) [61] Inaddition they concluded that the tissue distribution of fucox-anthin metabolites was not associated with their lipophilic-ity but depletion seemed to be slower because of theirhigher lipophilicity

Pharmacokinetics of drugs depends on species Mordenti[62] reported that the elimination of drugs was the fastestin mice and slowest in human subjects among the speciescomparedThe study byHashimoto et al [63] showed that thebioavailability of fucoxanthinol was higher in human subjectsthan in mice They also found that the metabolism of fucox-anthin differed between human subjects and mice Fucoxan-thinol is considered to be the primary active metabolite inhuman And no amarouciaxanthin A was detected in thevolunteerrsquos plasma

Solubility of fucoxanthin as an important factor mustbe considered for oral administration Maeda et al [64 65]found fucoxanthin was difficult to dissolve in soybean oiland vegetable oils whereas it could easily dissolve in fish oilandmedium-chain triacylglycerols (MCT)The gain of whiteadipose tissue (WAT) weight was less in KK-119860119910 mice fedfucoxanthin and fish oil than that in mice fed fucoxanthinalone [64] The expression of uncoupling protein 1 (UCP1)was more clear in mice fed fucoxanthin and MCT than thatin mice fed purified fucoxanthin or MCT alone [65] Thesedata indicated that the absorption rate of fucoxanthin couldbe increased by fish oil and MCT Moreover the study bySugawara et al [66] showed that lysophosphatidylcholine(lysoPC) and phospholipase A2 (PLA2) were of importancein enhancing the absorption of carotenoids in the digestivetract and supporting a simple diffusion mechanism for

Evidence-Based Complementary and Alternative Medicine 3

HO

HO

O

O

OH

OH

OH

OH

OCOCH3

Fucoxanthin

Fucoxanthinol

Amarouciaxanthin A

HO

O

O

O

OH

OH

∙

∙

∙

Figure 2 The chemical structures of fucoxanthin fucoxanthinol and amarouciaxanthin A

carotenoids assimilation by the intestinal epithelium Thusthe absorption rate of fucoxanthin could be significantlyaffected by some components especially lipids

4 Safety of Fucoxanthin

Fucoxanthin is a safe pharmaceutical ingredient Clinicalresearch showed that taking fucoxanthin was thought tospeed upmetabolism but the metabolic boost did not stimu-late the central nervous system [67] A 4-week toxicity studyon repeated oral dosing of fucoxanthin (95 purity) to ratswas carried out by Kadekaru et al [68] The results indicatedthat fucoxanthin did not show obvious toxicity in the rats[68] The toxicity of the extracts containing 00012 fucox-anthin was determined in mice by Zaragoza et al [69] Theextracts did not show any relevant toxicity effects in an acutetoxicity test after a 4-week daily treatment Furthermorefucoxanthinol the metabolite of fucoxanthin showed nosignificant adverse effects in vivo [70]

5 Pharmacological Activities of Fucoxanthin

51 Antiobesity Effect Long-term consumption of high fatdiets could alter lipid metabolism which lead to the accumu-lation of visceral fat and result in obesity and related disor-ders such as diabetes mellitus hypertension dyslipidemiaand cardiovascular disease disorders [71 72] Consequentlyfinding efficient strategies to prevent obesity is crucialResearchers found that fucoxanthin supplementation couldplay a beneficial role in antiobesity through various pathways(Figure 3)

Fucoxanthin significantly reduced plasma and hepatictriglyceride concentrations fecal triglyceride cholesteroland cholesterol-regulating enzyme activities such as 3-hydroxy-3-methylglutaryl coenzyme A reductase and acylcoenzyme A [11ndash15]

Fucoxanthin might affect the gene expression associatedwith lipid metabolism to lower the level of potential lipidHa and Kim [16] found that fucoxanthin supplementation


FucoxanthinMetabolize

mRNAof

MCP-1

mRNA ofACC FAS G6PDH

HMG-CoAmRNA of

LCAT CPT1and CYP7A1

mRNA ofUCP1 in

WAT

Amarouciaxanthin A

fucoxanthinol

Expression ofPPAR120574 CEBP120572

and SREBP1c

Improving lipid andcholesterolmetabolism

Suppressing 3T3-L1adipocyte differentiation

Antiobesity

and

uarr Upregulationdarr Downregulation

ACAT and SREBP-1c

Figure 3 Antiobesity of fucoxanthin uarr Upregulation darr downregulation

could decrease the mRNA expressions of hepatic acetyl-CoA carboxylase (ACC) fatty acid synthase (FAS) glucose-6-phosphate dehydrogenase (G6PDH) hydroxy-3-meth-ylglutaryl coenzyme A (HMG-CoA) acyl-CoA cholesterolacyltransferase (ACAT) and SREBP-1C in rats And themRNA expressions of lecithin-cholesterol acyltransferase(LCAT) CPT1 and CYP7A1 were significantly high in theHF + Fxn group Maeda et al [17] reported that dietaryadministration of high fat (HF) diet resulted in expressionof monocyte chemoattractant protein-1 (MCP-1) mRNA inmice But the increased expression ofMCP-1mRNAwas nor-malized by the fucoxanthin-rich Wakame lipids (WLs) Theresults suggested thatWLs diet could ameliorate high fat (HF)diet induced lipid metabolism disorders in mice Woo et al[11] discovered that the activities of two key cholesterolregulating enzymes acyl coenzyme A cholesterol acyltrans-ferase and 3-hydroxy-3-methylglutaryl coenzyme A reduc-tase were significantly inhibited by fucoxanthin in miceRelative mRNA expressions of acyl-coA oxidase 1 palmitoyl(ACOX1) and peroxisome proliferator-activated receptor 120572(PPAR120572) and 120574 (PPAR120574) were also obviously altered by fucox-anthin in the liver

Recent studies showed that progression of 3T3-L1 pread-ipocyte differentiation is divided into early (days 0ndash2 D0ndashD2) intermediate (days 2ndash4 D2ndashD4) and late stages (day4 onwards D4-) [18] Fucoxanthin presents different effectson 3T3-L1 cells during the three differentiation stages Kanget al [19] reported that when fucoxanthin presented duringthe early stage of differentiation (D0ndashD2) it promoted 3T3-L1adipocyte differentiation and increased protein expressionsof peroxisome proliferator-activated receptor 120574 (PPAR120574)

CCAATenhancer-binding protein 120572 (CEBP120572) sterol reg-ulator element-binding protein 1c (SREBP1c) aP2 and adi-ponectin However fucoxanthin showed the inhibition tointercellular lipid accumulation by reducing the expressionsof PPAR120574 CEBP120572 and SREBP1c during the intermediate(D2ndashD4) and late stages (D4ndashD7) of differentiation [19]In addition fucoxanthinol the metabolite of fucoxanthindownregulated PPAR120574 and exhibited stronger suppressiveeffects than fucoxanthin on adipocyte differentiation in 3T3-L1 cells [20] Amarouciaxanthin A another metabolite offucoxanthin also showed the suppression to the expressionsof PPAR120574 and CEBP120572 during adipocyte differentiationFurthermore amarouciaxanthin A showed stronger suppres-sive effect on glycerol-3-phosphate dehydrogenase (GPDH)activity than fucoxanthinol Compared with fucoxanthinolamarouciaxanthin A markedly downregulated the mRNAexpressions of adipocyte fatty acid binding protein (aP2)lipoprotein lipase (LPL) and glucose-transporter 4 (Glut4)in 3T3-L1 cells [21]

Many studies suggested that fucoxanthin played an antio-besity effect by stimulating the expression of uncouplingprotein 1 (UCP1) in white adipose tissue (WAT) UCP1 isusually found in brown adipose tissue (BAT) which is notexpressed in WAT without stimulation However Maedaet al [22] detected clear signals ofUCP1 protein andmRNA inWAT when the mice were fedUndaria pinnatifida lipids con-taining fucoxanthin Furthermore they also [64] discoveredthat 02 fucoxanthin in the diet significantly attenuated thegain of WAT weight in KK-119860119910 mice with increasing UCP-1expression


Fucoxanthin could stimulate the 120573-oxidation activity andinhibit the phosphatidate phosphohydrolase activity resultingin a decrease in the hepatic lipid droplet accumulation[12] High fat diet induced the decrease in phosphorylationof AMP-activated protein kinase (AMPK) and acetyl-CoAcarboxylase (ACC)The decrease could be restored by fucox-anthin with increasing LKB1 phosphorylation inmature 3T3-L1 adipocytes [23]

Fucoxanthinmight alter plasma leptin level Leptin secre-tions are elevated by the accumulation of fat in adipocytesLeptin could control bodyweight and adipose fat pad throughthe regulation of the energy expenditure [24] Park et al[12] evaluated the beneficial effect of Undaria pinnatifidaethanol extract (UEFx) in C57BL6J mice They found thatfucoxanthin could significantly decrease plasma leptin levelwhich was associated with a significant decrement of theepididymal adipose tissue weight

One study conducted in human suggested the effectsof fucoxanthin on weight loss The combination of 300mgpomegranate seed oil and 300mgbrown seaweed extract con-taining 24mg fucoxanthin significantly resulted in the reduc-tion of body weight and liver fat content in obese womenwhowere treated for 16 days [25]

52 Antitumorigenic Activity Chemotherapy is a conven-tional way to decrease the rate of cancer mortality How-ever the recurrence and morbidity of cancer could not bedecreased through chemotherapy Therefore it is essentialto find a promising approach to control the developmentof cancer Fucoxanthin can be an effective way to controlmalignancies by inducing cell cycle arrest and apoptosis

521 Cell Cycle Arrest GADD45 is involved in growth sup-pression PCNA is a normal component of cyclin-dependentkinases (Cdk) complexes and a protein involved in DNAreplication and repair Smith et al [26] previously found thatwhen GADD45 bound to PCNA it would stimulate DNAexcision repair in vitro and inhibit entry of cells into S phaseIn addition GADD45A enhanced the interaction between 120573-catenin and Caveolin-1 which induced 120573-catenin transloca-tion to cell membrane resulting in cell-cell adhesioncontactinhibition [27] Yoshiko and Hoyoko [28] found that fucox-anthin markedly induced GADD45A in HepG2 and DU145cells at the G1 arrest The induction of GADD45A expressionand G1 arrest by fucoxanthin was positively regulated byinhibiting p38 MAPK pathway in HepG2 cells and nega-tively regulated by inhibiting SAPKJNK pathway in DU145cells [29] In addition inhibition of ERK by fucoxanthinonly enhanced GADD45A expression and had no influenceson G1 arrest in HepG2 cells These results suggested thatdifferent patterns of MAPK involvement in the induction ofGADD45A andG1 arrest by fucoxanthinwere associatedwiththe cell type

The study by Kim et al [30] demonstrated that fucoxan-thin decreased the proliferation of B16F10 cells accompaniedby the induction of cell cycle arrest during the G(0)G(1)phase The cell cycle arrest during the G(0)G(1) phaseinduced by fucoxanthin was related to a significant decrease

in the protein expressions of phosphorylated-Rb (retinoblas-toma protein) cyclin D (1 and 2) and cyclin-dependentkinase (CDK4) and significant upregulation of the proteinlevels of p15INK4B and p27Kip1 [30] Yu et al [31] reported thatfucoxanthin induced apoptosis in human gastric adenocar-cinoma MGC-803 cells and cell cycle arrest in G2M phaseFucoxanthinmarkedly decreased the expressions of CyclinB1surviving and STAT3 inMGC-803 cells in a dose-dependentmanner [31]They also found that fucoxanthin could suppressthe expression of CyclinB1 through the JAKSTAT signalpathway [31] The mechanism of cell cycle arrest induced byfucoxanthin was described in a picture (Figure 4)

522 Apoptosis Induced by Fucoxanthin and FucoxanthinolApoptosis is a process of physiological cell removal whichregulates the balance between cell proliferation and cell death[32] The induction of apoptosis is now considered to be aneffective way for cancer therapy [33 34]

Recent studies revealed that STATs played an importantrole in maintaining EGFR-mediated cancer cell proliferation[35 36] Thus inhibiting EGFR in conjunction with STATswould be a promising and attractive therapeutic strategy forcancers [37] Wang et al [38] investigated the antitumormechanisms of fucoxanthin on xenografted sarcoma 180(S180) in miceThe results showed that fucoxanthin inhibitedthe expressions of bcl-2 EGFR STAT3 and phosphorylatedSTAT3 proteins and enhanced the expression of cleavedcaspase-3 Therefore through downregulating STAT3EGFRsignaling fucoxanthin can induce apoptosis in S180 xeno-grafts-bearing mice

Both fucoxanthin and its metabolite fucoxanthinol caninduce apoptosis Ishikawa et al [70] found that fucoxanthinand fucoxanthinol could inhibit cell viability of HTLV-1-infected T-cell lines and ATL cells and induce apoptosis byreducing the expressions of Bcl-2 XIAP cIAP2 and survivinFurthermore uninfected cell lines and normal peripheralblood mononuclear cells were resistant to fucoxanthin andfucoxanthinol The study by Yamamoto et al [39] showedthat fucoxanthin and fucoxanthinol induced cell cycle arrestduringG1 phase and caspase-dependent apoptosis in primaryeffusion lymphoma cells The apoptosis-inducing activity offucoxanthinol was more potent than that of fucoxanthin

53 Antidiabetic Activity In general consuming nutrition-ally rich diets and irrational dietary habits could result in obe-sity and diabetes mellitus Diabetes mellitus is usually causedby obesity because excessive energy intake and accumulationof lipids can elevate insulin resistance [40] Fucoxanthin wasdemonstrated to play an important role in reducing insulinresistance and blood glucose

Saturated fat intake can elevate the HbA1c level [41]The HbA1c level is a risk indicator of glycemia and diabeticcomplications [42]The study ofWoo et al [11] suggested thatsupplementation of 005 and 02 fucoxanthin significantlyreduced the blood HbA1c and plasma insulin level comparedwith the control group

The adipokine tumor necrosis factor-120572 (TNF120572) is involvedin the development of type 2 diabetes TNF120572 is elevated in


Fucoxanthin

JAKSTAT p38MAPK SPAKJNKP27Kip1

P15INKB

CyclinB1

GADD45A 120573-catenin Cyclin D1D2

CDK

M

G2 G0G1

S

Cellproliferation

PCNA


Figure 4 Fucoxanthin on cell cycle arrest uarr Upregulation darr downregulation

obesity and positively associated with insulin resistance [4344] The study by Maeda et al [64] showed that 02 fucox-anthin improved insulin resistance and markedly decreasedthe blood glucose and plasma insulin concentrations in KK-119860119910 mice by downregulating TNF120572 mRNA Maeda et al [17]

also investigated that the fucoxanthin-rich Wakame lipids(WLs) diet could ameliorate insulin resistance by promotingexpression of glucose transporter 4 (GLUT4) mRNA inskeletal muscle tissues

Blood glucose level was positively associated with hepaticgluconeogenic enzyme activities but negatively associatedwith hepatic glucokinase activity [12] Park et al [12] foundthat fucoxanthin could decrease insulin resistance by elevat-ing the ratio of hepatic glucokinaseglucose-6-phosphataseand glycogen content

54 Antioxidative Activity Fucoxanthin is considered as apotential antioxidant because of its unique chemical structureincluding an allenic bond epoxide group andhydroxyl group[10] Previous studies showed that fucoxanthin possessedan effective radical scavenging ability [45 58] Kawee-aiet al [58] discovered that fucoxanthin showed strong activityagainst BchE with an IC50 value of 197Mm and mixedinhibition type But fucoxanthin exhibited weak activityagainst AChE When the percent of cis-isomer increased by2 the scavenging activity against DPPH superoxide anionhydrogen peroxide and reducing power decreased by 210103 160 and 197 respectively [58] The antioxidant effectof fucoxanthin was determined by Ha et al in vivo [46] Inexperiments the markers of antioxidant capacity like plasmatotal antioxidant capacity (TAC) and activities of antioxidant

enzymes such as catalase superoxide dismutase (SOD)were determined in rats fed HF diet and HF + Fxn dietGlutathione peroxidase (GSH-Px) and mRNA expressions oftranscription factor and nuclear erythroid factor like 2 (Nrf2)as well as its target genes such as NAD(P)H quinone oxidore-ductase 1 (NQO1) were also determined The result showedthat the activity of GSH-Px in plasma and liver was both sig-nificantly elevated by fucoxanthin supplementation PlasmaTAC level and mRNA expressions of Nrf2 and NQO1 werealso obviously higher in the HF + Fxn group than those inthe HF group [46]

55 Anti-InflammatoryActivity Previous studies determinedthat anti-inflammatory agents should reduce the inflamma-tory response by suppressing the inflammatory mediatorsincluding nutric oxide (NO) prostaglandin E

2(PGE2) tumor

necrosis factor-120572 (TNF120572) interleukin- (IL-) 1120573 IL-6 andinflammatory cytokines such as cyclooxygenase (COX) andinducible nutric oxide synthase (iNOS) [47] Kim et al [48]investigated the anti-inflammatory effect of fucoxanthin inlipopolysaccharide- (LPS-) stimulated murine macrophageRAW 2647 cells The results demonstrated that fucoxanthincould reduce the levels of proinflammatorymediators includ-ing NO PGE

2 IL-1120573 TNF120572 and IL-6 by suppressing the NF-

120581B activation and the MAPK phosphorylation Additionallyfucoxanthin reduced the levels of iNOS and COX-2 proteinsin a dose-dependent manner [48] Sakai et al [49] authen-ticated the anti-inflammatory and antiallergenic propertiesof fucoxanthin in vivo The result showed that fucoxanthincould markedly inhibit the antigen-induced release of 120573-hexosaminidase in rat basophilic leukemia 2H3 cells and


bone marrow-derived mast cells Furthermore fucoxanthinsuppressed antigen-induced aggregation of the high affinityIgE receptor (Fc isin RI) and Fc isin RI-mediated intracellularsignaling It suggested that fucoxanthin inhibited the degran-ulation of mast cells by suppressing the aggregation of Fc isinRI[49]

56 Hepatoprotective Effect Increasing fatty acid oxidationand decreasing the amounts of fatty acids as substratesfor triacylglycerol synthesis could improve fatty liver [12]Fucoxanthin could increase fatty acid oxidation and decreasethe hepatic lipid contents by regulating activities of hepaticlipid metabolic enzymes and stimulating 120573-oxidation activity[11 12] Woo et al [11] found that fucoxanthin supple-mentation significantly decreased the hepatic lipid contentsand the concentration of plasma triglyceride in C57BL6Nmice The mechanism is that fucoxanthin inhibited theactivities of hepatic lipogenic enzymes glucose-6-phosphatedehydrogenase malic enzyme fatty acid synthase and phos-phatidate phosphohydrolase as well as elevated 120573-oxidationactivity Furthermore Park et al [12] also demonstrated thatfucoxanthin supplementation stimulated120573-oxidation activityand reduced the phosphatidate phosphohydrolase activityresulting in the hepatic lipid droplet

Docosahexaenoic acid (DHA) is an important n-3 func-tional polyunsaturated fatty acid in biological systems [50]Fucoxanthinwas reported to promote the proportion ofDHAandAA in liver lipids of mice [50ndash52] DHA andAA contentsin the liver lipids could be also enhanced by fucoxanthinol[51 52]

Liu et al [53] demonstrated that pretreatment with fucox-anthin (1ndash20120583M) for 24 h could protect the murine hepaticBNL CL2 cells against oxidative damage induced by ferricnitrilotriacetate (Fe-NTA) They [53] found that when theincubation of BNL CL2 cells was treated with Fe-NTA for30min cell proliferation was obviously decreased Howeverfucoxanthin significantly recovered cell proliferation in adose-dependent manner Furthermore the data suggestedthat fucoxanthin not only decreased the level of thiobar-bituric acid-reactive substances (TBARS) and protein car-bonyl contents but also increased the level of GSH in aconcentration-dependent manner All the results indicatedthat fucoxanthin could inhibit cytotoxicity in hepatic BNLCL2 cells induced by Fe-NTA

57 Cardiovascular and Cerebrovascular Protective Effects Alipid profile is a risk factor of cardiovascular disease Fucoxan-thin can improve the lipid profile and prevent the damage incardiovascular system by promoting the proportion of DHAin the liver [12]

Hypertension is associated with cerebrovascular diseasesIkeda et al [54] examined the effect ofWakame on the devel-opment of stroke in stroke-prone spontaneously hypertensiverats (SHRSP) They found that the development of strokesigns was significantly delayed and the survival rate of SHRSPwas significantly improved by Wakame However the bloodpressure showed no significant difference among groupsThe results indicated thatWakame improved cerebrovascular

diseases in SHRSP independent of hypertension They alsofound that fucoxanthin isolated from Wakame may have apreventive effect on ischaemic cultured neuronal cell deathIn addition fucoxanthin could obviously attenuate neuronalcell injury in hypoxia and reoxygenation

6 Conclusion

Fucoxanthin is a special carotenoid and has many bioactiv-ities The results of animal studies showed that fucoxanthinhad potential value in preventing and treating lifestyle-relateddiseases as obesity diabetes cancer cardiovascular diseaseand other chronic diseases Though there are a few studiesin human subjects more clinical trials should be conductedFucoxanthin is proved to have no side effects and can be easilyextracted frommacroalgae and microalgae Additionally themethods to improve its stability and bioavailability havebeen studied With previous documents and further clinicalresearches fucoxanthin will be easier to be developed intosafe marine drugs and nutritional products to prevent andtreat lifestyle-related diseases

Conflict of Interests

The authors declare that there is no conflict of interests

Authorsrsquo Contribution

Hui Zhang and Yibo Tang contributed equally to this work

Acknowledgments

This studywas supported by Program forNewCentury Excel-lent Talents in University (NCET-10-0273) Beijing NovaProgram (2010B035) National Natural Science Foundationof China (81373780) Foundation of Jinan Science and Tech-nology Development Program (201303055) and Project ofShandongProvinceHigher Educational Science andTechnol-ogy Program (J14LK61)

References

[1] R S Kuipers D J de Graaf M F Luxwolda M H A MuskietD A J Dijck-Brouwer and F A J Muskiet ldquoSaturated fatcarbohydrates and cardiovascular diseaserdquo The NetherlandsJournal of Medicine vol 69 no 9 pp 372ndash378 2011

[2] F Beppu Y Niwano T TsukuiMHosokawa andKMiyashitaldquoSingle and repeated oral dose toxicity study of fucoxanthin(FX) a marine carotenoid in micerdquoThe Journal of ToxicologicalSciences vol 34 no 5 pp 501ndash510 2009

[3] SM Kim Y-J JungO-N Kwon et al ldquoA potential commercialsource of fucoxanthin extracted from the microalga Phaeo-dactylum tricornutumrdquo Applied Biochemistry and Biotechnol-ogy vol 166 no 7 pp 1843ndash1855 2012

[4] G Englert T Bjoslashrnland and S Liaaen-Jensen ldquo1D and 2DNMR study of some allenic carotenoids of the fucoxanthinseriesrdquoMagnetic Resonance in Chemistry vol 28 no 6 pp 519ndash528 1990


[5] M Hosokawa T Okada N Mikami I Konishi and K Miya-shita ldquoBio-functions of marine carotenoidsrdquo Food Science andBiotechnology vol 18 no 1 pp 1ndash11 2009

[6] X Yan Y Chuda M Suzuki and T Nagata ldquoFucoxanthin asthe major antioxidant in Hijikia fusiformis a common edibleseaweedrdquo Bioscience Biotechnology and Biochemistry vol 63no 3 pp 605ndash607 1999

[7] V M Dembitsky and T Maoka ldquoAllenic and cumulenic lipidsrdquoProgress in Lipid Research vol 46 no 6 pp 328ndash375 2007

[8] N Achir V A Randrianatoandro P Bohuon A Laffargue andS Avallone ldquoKinetic study of120573-carotene and lutein degradationin oils during heat treatmentrdquo European Journal of Lipid Scienceand Technology vol 112 no 3 pp 349ndash361 2010

[9] D Zhao S-M Kim C-H Pan and D Chung ldquoEffects of heat-ing aerial exposure and illumination on stability of fucoxanthinin canola oilrdquo Food Chemistry vol 145 pp 505ndash513 2014

[10] R K Sangeetha N Bhaskar and V Baskaran ldquoComparativeeffects of beta-carotene and fucoxanthin on retinol deficiencyinduced oxidative stress in ratsrdquo Molecular and Cellular Bio-chemistry vol 331 no 1-2 pp 59ndash67 2009

[11] M-N Woo S-M Jeon H-J Kim et al ldquoFucoxanthin supple-mentation improves plasma and hepatic lipid metabolism andblood glucose concentration in high-fat fed C57BL6N micerdquoChemico-Biological Interactions vol 186 no 3 pp 316ndash3222010

[12] H J Park M K Lee Y B Park Y C Shin and M S ChoildquoBeneficial effects of Undaria pinnatifida ethanol extract ondiet-induced-insulin resistance in C57BL6J micerdquo Food andChemical Toxicology vol 49 no 4 pp 727ndash733 2011

[13] M-N Woo S-M Jeon Y C Shin M-K Lee M A Kangand M-S Choi ldquoAnti-obese property of fucoxanthin is partlymediated by altering lipid-regulating enzymes and uncouplingproteins of visceral adipose tissue in micerdquoMolecular Nutritionamp Food Research vol 53 no 12 pp 1603ndash1611 2009

[14] S-M Jeon H-J Kim M-N Woo et al ldquoFucoxanthin-richseaweed extract suppresses body weight gain and improveslipid metabolism in high-fat-fed C57BL6J micerdquo BiotechnologyJournal vol 5 no 9 pp 961ndash969 2010

[15] X Hu Y Li C Li et al ldquoCombination of fucoxanthin and con-jugated linoleic acid attenuates body weight gain and improveslipid metabolism in high-fat diet-induced obese ratsrdquo Archivesof Biochemistry and Biophysics vol 519 no 1 pp 59ndash65 2012

[16] A W Ha andW K Kim ldquoThe effect of fucoxanthin rich poweron the lipid metabolism in rats with a high fat dietrdquo NutritionResearch and Practice vol 7 no 4 pp 287ndash293 2013

[17] H Maeda M Hosokawa T Sashima K Murakami-Funayamaand K Miyashita ldquoAnti-obesity and anti-diabetic effects offucoxanthin on diet-induced obesity conditions in a murinemodelrdquo Molecular Medicine Reports vol 2 no 6 pp 897ndash9022009

[18] J M Ntambi and Y C Kim ldquoAdipocyte differentiation and geneexpressionrdquo Journal of Nutrition vol 130 no 12 pp 3122ndash31262000

[19] S-I Kang H-C Ko H-S Shin et al ldquoFucoxanthin exerts dif-fering effects on 3T3-L1 cells according to differentiation stageand inhibits glucose uptake in mature adipocytesrdquo Biochemicaland Biophysical Research Communications vol 409 no 4 pp769ndash774 2011

[20] H Maeda M Hosokawa T Sashima N Takahashi T Kawadaand K Miyashita ldquoFucoxanthin and its metabolite fucox-anthinol suppress adipocyte differentiation in 3T3-L1 cellsrdquo

International Journal of Molecular Medicine vol 18 no 1 pp147ndash152 2006

[21] M-J YimMHosokawa YMizushinaH Yoshida Y Saito andK Miyashita ldquoSuppressive effects of amarouciaxanthin A on3T3-L1 adipocyte differentiation through down-regulation ofPPAR120574 and CEBP120572mRNA expressionrdquo Journal of Agriculturaland Food Chemistry vol 59 no 5 pp 1646ndash1652 2011

[22] H Maeda M Hosokawa T Sashima K Funayama and KMiyashita ldquoFucoxanthin from edible seaweed Undaria pin-natifida shows antiobesity effect through UCP1 expression inwhite adipose tissuesrdquo Biochemical and Biophysical ResearchCommunications vol 332 no 2 pp 392ndash397 2005

[23] S I Kang H S Shin H M Kim et al ldquoPetalonia binghamiaeextract and its constituent fucoxanthin ameliorate high-fat diet-induced obesity by activating AMP-activated protein kinaserdquoJournal of Agricultural and Food Chemistry vol 60 no 13 pp3389ndash3395 2012

[24] M A Pelleymounter M J Cullen M B Baker et al ldquoEffectsof the obese gene product on body weight regulation in obobmicerdquo Science vol 269 no 5223 pp 540ndash543 1995

[25] M Abidov Z Ramazanov R Seifulla and S Grachev ldquoTheeffects of Xanthigen in the weight management of obese pre-menopausal women with non-alcoholic fatty liver disease andnormal liver fatrdquo Diabetes Obesity and Metabolism vol 12 no1 pp 72ndash81 2010

[26] M L Smith I T Chen Q Zhan et al ldquoInteraction of thep53-regulated protein gadd45 with proliferating cell nuclearantigenrdquo Science vol 266 no 5189 pp 1376ndash1380 1994

[27] J Ji R Liu T Tong et al ldquoGadd45a regulates 120573-catenin distri-bution andmaintains cell-cell adhesioncontactrdquoOncogene vol26 no 44 pp 6396ndash6405 2007

[28] S Yoshiko and N Hoyoko ldquoFucoxanthin a natural carotenoidinduces G1 arrest and GADD45 gene expression in humancancer cellsrdquo In Vivo vol 21 no 2 pp 305ndash309 2007

[29] Y Satomi and H Nishino ldquoImplication of mitogen-activatedprotein kinase in the induction ofG1 cell cycle arrest and gadd45expression by the carotenoid fucoxanthin in human cancercellsrdquo Biochimica et Biophysica Acta vol 1790 no 4 pp 260ndash266 2009

[30] K-N Kim G Ahn S-J Heo et al ldquoInhibition of tumor growthin vitro and in vivo by fucoxanthin against melanoma B16F10cellsrdquo Environmental Toxicology and Pharmacology vol 35 no1 pp 39ndash46 2013

[31] R X Yu X M Hu S Q Xu Z J Jiang and W Yang ldquoEffectsof fucoxanthin on proliferation and apoptosis in human gastricadenocarcinomaMGC-803 cells via JAKSTAT signal pathwayrdquoEuropean Journal of Pharmacology vol 657 no 1ndash3 pp 10ndash192011

[32] T Rengarajan P Rajendran N Nandakumar M P Balasub-ramanian and I Nishigaki ldquoCancer preventive efficacy ofmarine carotenoid fucoxanthin cell cycle arrest and apoptosisrdquoNutrients vol 5 no 12 pp 4978ndash4989 2013

[33] C B Thompson ldquoApoptosis in the pathogenesis and treatmentof diseaserdquo Science vol 267 no 5203 pp 1456ndash1462 1995

[34] L A Smets ldquoProgrammed cell death (apoptosis) and responseto anti-cancer drugsrdquo Anti-Cancer Drugs vol 5 no 1 pp 3ndash91994

[35] J I Song and J R Grandis ldquoSTAT signaling in head and neckcancerrdquo Oncogene vol 19 no 21 pp 2489ndash2495 2000

[36] G Berclaz H J Altermatt V Rohrbach A Siragusa E Dreherand P D Smith ldquoEGFR dependent expression of STAT3 (but


not STAT1) in breast cancerrdquo International Journal of Oncologyvol 19 no 6 pp 1155ndash1160 2001

[37] K M Quesnelle A L Boehm and J R Grandis ldquoSTAT-medi-ated EGFR signaling in cancerrdquo Journal of Cellular Biochemistryvol 102 no 2 pp 311ndash319 2007

[38] J Wang S Chen S Xu et al ldquoIn vivo induction of apoptosisby fucoxanthin a marine carotenoid associated with down-regulating STAT3EGFR signaling in sarcoma 180 (S180) xeno-grafts-bearing micerdquo Marine Drugs vol 10 no 9 pp 2055ndash2068 2012

[39] K Yamamoto C Ishikawa H Katano T Yasumoto and NMori ldquoFucoxanthin and its deacetylated product fucoxanthi-nol induce apoptosis of primary effusion lymphomasrdquo CancerLetters vol 300 no 2 pp 225ndash234 2011

[40] L A Campfield and F J Smith ldquoThe pathogenesis of obesityrdquoBaillierersquos Best Practice amp Clinical Endocrinology amp Metabolismvol 13 no 1 pp 13ndash30 1999

[41] A-HHarding L A Sargeant AWelch et al ldquoFat consumptionand HbA

1119888

levels the EPIC-norfolk studyrdquo Diabetes Care vol24 no 11 pp 1911ndash1916 2001

[42] D E Goldstein R R Little R A Lorenz J I Malone DNathan and C M Peterson ldquoTests of glycemia in diabetesrdquoDiabetes Care vol 18 no 6 pp 896ndash909 1995

[43] G S Hotamisligil N S Shargill and B M Spiegelman ldquoAdi-pose expression of tumor necrosis factor-alpha direct role inobesity-linked insulin resistancerdquo Science vol 259 no 5091 pp87ndash91 1993

[44] G S Hotamisligil P Arner J F Caro R L Atkinson and BM Spiegelman ldquoIncreased adipose tissue expression of tumornecrosis factor-120572 in human obesity and insulin resistancerdquoTheJournal of Clinical Investigation vol 95 no 5 pp 2409ndash24151995

[45] T Nomura M Kikuchi A Kubodera and Y KawakamildquoProton-donative antioxidant activity of fucoxanthin with 11-diphenyl-2-picrylhydrazyl (DPPH)rdquo Biochemistry and Molecu-lar Biology International vol 42 no 2 pp 361ndash370 1997

[46] A W Ha S J Na and W K Kim ldquoAntioxidant effects offucoxanthin rich powder in rats fedwith high fat dietrdquoNutritionResearch and Practice vol 7 no 6 pp 475ndash480 2013

[47] S-J Lee S-K Bai K-S Lee et al ldquoAstaxanthin inhibitsnitric oxide production and inflammatory gene expression bysuppressing I120581Bkinase-dependentNF-120581BactivationrdquoMoleculesand Cells vol 16 no 1 pp 97ndash105 2003

[48] K-N Kim S-J Heo W-J Yoon et al ldquoFucoxanthin inhibitsthe inflammatory response by suppressing the activation ofNF-120581B and MAPKs in lipopolysaccharide-induced RAW 2647macrophagesrdquo European Journal of Pharmacology vol 649 no1ndash3 pp 369ndash375 2010

[49] S Sakai T Sugawara K Matsubara and T Hirata ldquoInhibitoryeffect of carotenoids on the degranulation of mast cells viasuppression of antigen-induced aggregation of high affinity IgEreceptorsrdquo The Journal of Biological Chemistry vol 284 no 41pp 28172ndash28179 2009

[50] H Maeda T Tsukui T Sashima M Hosokawa and K Miya-shita ldquoSeaweed carotenoid fucoxanthin as a multi-functionalnutrientrdquo Asia Pacific Journal of Clinical Nutrition vol 17 no 1pp 196ndash199 2008

[51] T Tsukui K Konno M Hosokawa H Maeda T Sashimaand K Miyashita ldquoFucoxanthin and fucoxanthinol enhancethe amount of docosahexaenoic acid in the liver of KKAyobesediabetic micerdquo Journal of Agricultural and Food Chem-istry vol 55 no 13 pp 5025ndash5029 2007

[52] T Tsukui N BabaMHosokawa T Sashima and KMiyashitaldquoEnhancement of hepatic docosahexaenoic acid and arachi-donic acid contents in C57BL6J mice by dietary fucoxanthinrdquoFisheries Science vol 75 no 1 pp 261ndash263 2009

[53] C-L Liu A-L Liang and M-L Hu ldquoProtective effects offucoxanthin against ferric nitrilotriacetate-induced oxidativestress in murine hepatic BNL CL2 cellsrdquo Toxicology in Vitrovol 25 no 7 pp 1314ndash1319 2011

[54] K Ikeda A Kitamura H Machida et al ldquoEffect of Undariapinnatifida (Wakame) on the development of cerebrovasculardiseases in stroke-prone spontaneously hypertensive ratsrdquoClin-ical and Experimental Pharmacology and Physiology vol 30 no1-2 pp 44ndash48 2003

[55] R Aman A Schieber and R Carle ldquoEffects of heating andillumination on transminuscis isomerization and degradation of 120573-carotene and lutein in isolated spinach chloroplastsrdquo Journal ofAgricultural and Food Chemistry vol 53 no 24 pp 9512ndash95182005

[56] L K Henry G L Catignani and S J Schwartz ldquoOxidativedegradation kinetics of lycopene lutein and 9-cis and all-trans120573-carotenerdquo Journal of the American Oil Chemistsrsquo Society vol75 no 7 pp 823ndash829 1998

[57] B H Chen and J H Huang ldquoDegradation and isomerizationof chlorophyll a and 120573-carotene as affected by various heatingand illumination treatmentsrdquo Food Chemistry vol 62 no 3 pp299ndash307 1998

[58] A Kawee-ai A Kuntiya and S M Kim ldquoAnticholinesteraseand antioxidant activities of fucoxanthin purified from themicroalga Phaeodactylum tricornutumrdquo Natural Product Com-munications vol 8 no 10 pp 1381ndash1386 2013

[59] AAsai T SugawaraHOno andANagao ldquoBiotransformationof fucoxanthinol into amarouciaxanthin a in mice and HepG2cells formation and cytotoxicity of fucoxanthin metabolitesrdquoDrug Metabolism and Disposition vol 32 no 2 pp 205ndash2112004

[60] T Hashimoto Y Ozaki M Taminato et al ldquoThe distributionand accumulation of fucoxanthin and its metabolites after oraladministration inmicerdquoBritish Journal of Nutrition vol 102 no2 pp 242ndash248 2009

[61] L Yonekura M Kobayashi M Terasaki and A Nagao ldquoKeto-carotenoids are the major metabolites of dietary lutein andfucoxanthin inmouse tissuesrdquoThe Journal of Nutrition vol 140no 10 pp 1824ndash1831 2010

[62] J Mordenti ldquoMan versus beast pharmacokinetic scaling inmammalsrdquo Journal of Pharmaceutical Sciences vol 75 no 11pp 1028ndash1040 1986

[63] T Hashimoto Y Ozaki MMizuno et al ldquoPharmacokinetics offucoxanthinol in human plasma after the oral administration ofkombu extractrdquo British Journal of Nutrition vol 107 no 11 pp1566ndash1569 2012

[64] H Maeda M Hosokawa T Sashima and K MiyashitaldquoDietary combination of fucoxanthin and fish oil attenuates theweight gain of white adipose tissue and decreases blood glucosein obesediabetic KK-Ay micerdquo Journal of Agricultural and FoodChemistry vol 55 no 19 pp 7701ndash7706 2007

[65] H Maeda M Hosokawa T Sashima K Funayama and KMiyashita ldquoEffect of medium-chain triacylglycerols on anti-obesity effect of fucoxanthinrdquo Journal of Oleo Science vol 56no 12 pp 615ndash621 2007

[66] T Sugawara M Kushiro H Zhang E Nara H Ono and ANagao ldquoLysophosphatidylcholine enhances carotenoid uptake


from mixed micelles by Caco-2 human intestinal cellsrdquo Journalof Nutrition vol 131 no 11 pp 2921ndash2927 2001

[67] G Riccioni N DrsquoOrazio S Franceschelli and L SperanzaldquoMarine carotenoids and cardiovascular risk markersrdquo MarineDrugs vol 9 no 7 pp 1166ndash1175 2011

[68] T Kadekaru H Toyama and T Yasumoto ldquoSafety evaluation offucoxanthin purified from Undaria pinnatifidardquo Nippon Shok-uhin Kagaku Kogaku Kaishi vol 55 no 6 pp 304ndash308 2008

[69] M C Zaragoza D Lopez M P Saiz et al ldquoToxicity and anti-oxidant activity in vitro and in vivo of two Fucus vesiculosusextractsrdquo Journal of Agricultural and Food Chemistry vol 56no 17 pp 7773ndash7780 2008

[70] C Ishikawa S Tafuku T Kadekaru et al ldquoAntiadult T-cellleukemia effects of brown algae fucoxanthin and its deacety-lated product fucoxanthinolrdquo International Journal of Cancervol 123 no 11 pp 2702ndash2712 2008

[71] E A Lew and L Garfinkel ldquoVariations in mortality by weightamong 750000 men and womenrdquo Journal of Chronic Diseasesvol 32 no 8 pp 563ndash576 1979

[72] J M Olefsky R R Revers M Prince et al ldquoInsulin resistancein non-insulin dependent (type II) and insulin dependent (typeI) diabetes mellitusrdquo Advances in Experimental Medicine andBiology vol 189 pp 176ndash205 1985

Submit your manuscripts athttpwwwhindawicom

Stem CellsInternational

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Immunology ResearchHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinsonrsquos Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttpwwwhindawicom


HO

O

O

OH

C

OCOCH3

Figure 1 The chemical structure of fucoxanthin

structure are necessary to be well known Fucoxanthin is acharacteristic carotenoid which was found in brown algaeStructure of fucoxanthin (Figure 1) is similar to neoxanthindinoxanthin and peridinin Unlike other carotenoids fucox-anthin has a unique structure in which an unusual allenicbond 9 conjugated double bounds a 56-monoepoxide andsome oxygenic functional groups including hydroxyl epoxycarbonyl and carboxyl moieties are present [55 56]

Like other carotenoids fucoxanthin was ready to bedegraded during storage as a result of exposure to heat lightoxygen enzymes unsaturated lipids and other prooxidantmolecules [55]The formation of some cis-isomers by isomer-ization would happen which was related to treatment condi-tions and medium and type of carotenoids [55ndash57] Purifiedfucoxanthin usually resulted in three main peaks consistingof the trans-form along with two isomers [58] The ratio ofcis-isomers of fucoxanthin was increased with the increaseof extraction temperature [58] Kawee-ai et al also foundthat when the ratio of cis-isomers increased the antioxidantactivities of fucoxanthin decreased [58] A spectrophotomet-ric analysis about fucoxanthin in canola oil was analyzed byZhao et al [9] The results showed that heating caused thedegradation of total and all-trans fucoxanthin between 25 and100∘C in the absence of light and air [9] With the increaseof heating temperature the formation of 13-cis and 131015840-cisand the degradation of 91015840-cis would also be promoted Andthe process was found to follow simple first-order kineticsZhao et al [9] also found the degradation of all-trans and13-cis and 131015840-cis fucoxanthin was synergistically promotedwhen exposed to both air and light [9]These studies providedessential background knowledge on the properties of fucox-anthin In the process of extracting purifying storing andusing of fucoxanthin the heating aerial exposure and illu-mination should be avoided as much as possible

3 Metabolism and Bioavailability ofFucoxanthin

The absorption and metabolism of fucoxanthin are closelyrelated to its bioavailability It is essential to know the meta-bolic process and the method to improve the bioavailabilityof fucoxanthin (Figure 2)

Fucoxanthinol and amarouciaxanthin A are the mainmetabolites of fucoxanthin Fucoxanthin seemed to be rap-idly hydrolyzed to fucoxanthinol in the gastrointestinal

tract within 2 h after the administration and no unchangedfucoxanthin was detected in the plasma or liver in mice[59] Fucoxanthinol was converted into amarouciaxanthin Awhich was predominantly shown in livermicrosomes ofmiceand in HepG2 cells [59] The study in vitro by Hashimotoet al [60] demonstrated that dietary fucoxanthin accumu-lated in the heart and liver as fucoxanthinol and in adiposetissue as amarouciaxanthin A

Yonekura et al [61] investigated the metabolism tissuedistribution and depletion of fucoxanthin in ICR miceThey found fucoxanthinol and amarouciaxanthin A in micepartitioned more into adipose tissues than into plasma liverand kidneyThe half-life of the depletion (11990512) of fucoxanthinmetabolites in adipose tissues (gt41 d) was longer than thatin plasma (116 d) liver (263 d) and kidneys (444 d) [61] Inaddition they concluded that the tissue distribution of fucox-anthin metabolites was not associated with their lipophilic-ity but depletion seemed to be slower because of theirhigher lipophilicity

Pharmacokinetics of drugs depends on species Mordenti[62] reported that the elimination of drugs was the fastestin mice and slowest in human subjects among the speciescomparedThe study byHashimoto et al [63] showed that thebioavailability of fucoxanthinol was higher in human subjectsthan in mice They also found that the metabolism of fucox-anthin differed between human subjects and mice Fucoxan-thinol is considered to be the primary active metabolite inhuman And no amarouciaxanthin A was detected in thevolunteerrsquos plasma

Solubility of fucoxanthin as an important factor mustbe considered for oral administration Maeda et al [64 65]found fucoxanthin was difficult to dissolve in soybean oiland vegetable oils whereas it could easily dissolve in fish oilandmedium-chain triacylglycerols (MCT)The gain of whiteadipose tissue (WAT) weight was less in KK-119860119910 mice fedfucoxanthin and fish oil than that in mice fed fucoxanthinalone [64] The expression of uncoupling protein 1 (UCP1)was more clear in mice fed fucoxanthin and MCT than thatin mice fed purified fucoxanthin or MCT alone [65] Thesedata indicated that the absorption rate of fucoxanthin couldbe increased by fish oil and MCT Moreover the study bySugawara et al [66] showed that lysophosphatidylcholine(lysoPC) and phospholipase A2 (PLA2) were of importancein enhancing the absorption of carotenoids in the digestivetract and supporting a simple diffusion mechanism for


HO

HO

O

O

OH

OH

OH

OH

OCOCH3

Fucoxanthin

Fucoxanthinol

Amarouciaxanthin A

HO

O

O

O

OH

OH

∙

∙

∙











mRNAof

MCP-1


HMG-CoAmRNA of

LCAT CPT1and CYP7A1

mRNA ofUCP1 in

WAT

Amarouciaxanthin A

fucoxanthinol


and SREBP1c



Antiobesity

and


ACAT and SREBP-1c





















Fucoxanthin


P15INKB

CyclinB1


CDK

M

G2 G0G1

S

Cellproliferation

PCNA









2(PGE2) tumor












6 Conclusion






Acknowledgments


References














































1119888








































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

















HO

HO

O

O

OH

OH

OH

OH

OCOCH3

Fucoxanthin

Fucoxanthinol

Amarouciaxanthin A

HO

O

O

O

OH

OH

∙

∙

∙











mRNAof

MCP-1


HMG-CoAmRNA of

LCAT CPT1and CYP7A1

mRNA ofUCP1 in

WAT

Amarouciaxanthin A

fucoxanthinol


and SREBP1c



Antiobesity

and


ACAT and SREBP-1c





















Fucoxanthin


P15INKB

CyclinB1


CDK

M

G2 G0G1

S

Cellproliferation

PCNA









2(PGE2) tumor












6 Conclusion






Acknowledgments


References














































1119888








































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of


















mRNAof

MCP-1


HMG-CoAmRNA of

LCAT CPT1and CYP7A1

mRNA ofUCP1 in

WAT

Amarouciaxanthin A

fucoxanthinol


and SREBP1c



Antiobesity

and


ACAT and SREBP-1c





















Fucoxanthin


P15INKB

CyclinB1


CDK

M

G2 G0G1

S

Cellproliferation

PCNA









2(PGE2) tumor












6 Conclusion






Acknowledgments


References














































1119888








































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of































Fucoxanthin


P15INKB

CyclinB1


CDK

M

G2 G0G1

S

Cellproliferation

PCNA









2(PGE2) tumor












6 Conclusion






Acknowledgments


References














































1119888








































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
























6 Conclusion






Acknowledgments


References














































1119888








































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of

























































1119888








































of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of





























of






Disease Markers



OncologyJournal of





PPAR Research



Journal of

ObesityJournal of
















review article fucoxanthin: a promising ... - hindawi

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