植物皮肤脱色剂的研究进展

植物皮肤脱色剂的研究进展ResearchAndDevelopmentOnPhyto-activesForSkinDepigmentation美与白Beautyandwhitening肤色决定因素•皮肤内色素Pigmentsinskin黑素Melanin类胡萝卜素Carotenoid血红蛋白比例Ratioofhemoglobin•皮肤厚薄Thicknessofskin表皮Epidermis真皮DermisCriticalfactorsforskincolor表皮黑素细胞的原子力显微镜观察Observationofepidermalmelanocytesunderatomforcemicroscope(AFM)矛盾Conflicts化学剂-----天然植物Chemicalreagentsnaturalplants•汞剂Mercurials•氢醌Hydroquinone•糖皮质激素Glucocorticoids•效果好，安全性差Goodinefficacy，butbadinsafety研究流程•1.植物筛选Plantscreening酪氨酸活性测定-蘑菇酪氨酸酶、人酪氨酸酶多巴色素自动氧化生成黑素测定Tyrosinaseactivitymeasurement-mushroomtyrosinaseandhumantyrosinaseDopamelaninautooxidationandmelaninformationmeasurement•2.有效性安全性验证Efficacyandsafetytests黑素瘤细胞培养Melanomacellculture人表皮黑素细胞培养Humanmelanocytesculture豚鼠皮肤试验Guineapigskintest人临床效果观察Humanclinicalstudyandobservation•3.活性基团,开发新药ActivegroupsandnewdrugdevelopmentStudyscheme酪氨酸多巴酪氨酸酶多巴醌谷胱甘肽or半胱氨酸多巴色素半胱氨酰多巴TRP-25，6-二羟吲哚5，6-二羟吲哚-2-羧酸(DHI)(DHICA)TRP-1DHI多聚体DHICA多聚体优黑素褐黑素TRP-1（多巴色素互变异构酶）TRP-2（5，6-二羟吲哚-2-羟酸聚合酶）主要机制Primarymechanisms•直接或间接抑制酪氨酸酶Directorindirectinhibitioneffectontyrosinase•还原剂和活性氧族Reducingreagentandreactiveoxygenspecies•降解酪氨酸酶Tyrosinasedegradation•抑制黑素体转运Inhibitionofmelanosometransportation•抑制炎症引起的合成黑素反应Inhibitionofinflammationinducedmelaninsynthesis•加速表皮更新Accelerateturnoverrateofepidermis直接或间接抑制酪氨酸酶Directorindirectinhibitioneffectontyrosinase熊果苷Arbutin(熊果、沙梨树叶)(Arctostaphylosuva-ursiL.Spreng;P.pyrifolia(Burm.)Nakaitreeleaves)芦荟苦素Aloesin(芦荟,Aloe)甲酯龙胆酸2,5-Methylhydroxybenzoicacid(Gentisicmethyl)(龙胆)(GentianascabraBge)生物类黄酮Bioflavonoid山奈酚（银杏）Kaempferol(Gingko)芹菜素（芹菜）OleanolicAcid/Apigenin(Celery)柚皮素（柚）Naringenin(CitrusgrandisL.Osbeck)熊果苷(arbutin)•抑制酪氨酸酶活性Inhibitionoftyrosinaseactivity•抑制TRP-2活性InhibitiononTRP-2activity•有效性Efficacy:黑素瘤细胞Melanoma人黑素细胞Humanmelanocytes动物模型Animalmodels人体临床试验Humanclinicalstudy熊果Arctostaphylosuva-ursiL.Spreng熊果苷Arbutin•熊果苷---------(Arbutin)•Alpha-熊果苷--------(Alpha-arbutin)•脱氧熊果苷-----------(Deoxyarbutin)芦荟苦素(aloesin)•竞争性抑制多巴氧化Competetivelyinhibitondopaoxidation•非竞争性抑制酪氨酸酶羟化Non-competetivelyinhibittyrosinasehydroxidation龙胆酯酸2,5-MethylHydroxybenzoicacid(Gentisicmethyl)草原龙胆Eustomaressellianum2,5-Methylhydroxybenzoicacid(Gentisicmethyl)•有效---选择性抑制酪氨酸酶,可能和铜离子鳌合相关Ineffect---Selectivelyinhibittyrosinaseandmaychelatewithcopperions•安全---减轻氢醌的细胞毒性对哺乳动物细胞无致畸性Safe---Reducecytotoxicitybyhydroquinoneandnoteratogenicityonmammaliancells生物类黄酮(bioflavonoid)银杏Gingko(GinkgobilobaL.)金银花Honeysuckle(LonicerajaponicaThunb)芸香科豆科伞形科银杏科菊科RutaceaeLeguminosaeUmbelliferaeGinkgoaceaeAsteraceae•黄酮醇---螯合铜离子，竞争性抑制酪氨酸酶活性Flavonol---Chelatecopperionsandcompetetivelyinhibittyrosinaseactivity•黄酮---非竞争性抑制酪氨酸酶活性Flavone---Non-competetivelyinhibittyrosinaseactivity•异黄酮---效果差Isoflavone---Donothavegoodeffect兼有清除自由基的酪氨酸酶抑制剂Tyrosinaseinhibitorwithfreeradicalscavengerfunction•多酚类Polyphenols——鞣花酸（石榴皮）Ellagicacid(megranateskin)白藜芦醇（葡萄酒）Resveratrol(Wine)茶多酚（绿茶）Teapolyphenol(Greentea)原花青素（葡萄籽）Procyanidins(Grapeseed)•桑辛素F（桑科）MoracinF(Moraceae)鞣花酸(ellagicacid)•非竞争性抑制酪氨酸酶Non-competetivelyinhibittyrosinaseactivity•清除氧自由基Eliminateoxidativefreeradicals•豚鼠试验Guineapigstudy石榴Megranate白藜芦醇(Resveratrol)•竞争性抑制Competetiveinhibition•桑树Mulberry---氧化白藜芦醇(oxyresveratrol)更强抑制DOPA氧化话性oxyresveratrolhavestrongerinhibitioneffectonDOPAoxidativeactivity虎杖PolygonumcuspidatumSieb茶多酚Teapolyphenol•绿茶Greentea•表没食子儿茶素没食子酸酯（EGCG)(-)-epigallocatechin-3-gallate(EGCG)绿茶Greentea其它多酚Otherpolyphenols•原花青素Procyanidins构树(papermulberry)桑白•桑科树根皮提纯-桑辛素F抑制酪氨酸酶Moraceaetreerootsandskinextracts-MoracinFInhibitionoftyrosinase•清除氧自由基Eliminatefreeradicals构树PapermulberryBroussonetiapapyrifera(Linn.)Vent.还原剂和活性氧族Reducingagentsandreactiveoxygenspecies•α－生育酚（植物油、坚果、日本山椒）α-tocopherols(vegetableoils,nuts,ZanthoxylumJaponica)•抑制黑素细胞膜脂质过氧化反应Inhibitiononmelanocytelipidmembraneperoxidation降解酪氨酸酶Tyrosinasedegradation不饱和脂肪酸Unsaturatedfattyacids激活酪氨酸酶降解酶Activationondegradationenzymesoftyrosinase抑制黑素体转运Inhoibitiononmelanosometransportation•大豆Soybean：两种丝氨酸蛋白酶抑制剂TwokindsofserineproteaseinhibitorsBowman-Birk胰蛋白酶抑制剂(BBI)Bowman-Birktrypsininhibitor(BBI)大豆胰蛋白酶抑制剂(STI)Soybeantrypsininhibitor(STI)•干扰蛋白酶活化受体-2途径Interferewithproteaseactivatedreceptor-2(PAR-2)pathway烟酰胺(niacinamide)•抑制黑素体转运Inhibitiononmelanosometransportation•抗糖基化Anti-advancedglycation抑制炎症引起的合成黑素反应Inhibitionofinflammationinducedmelaninsynthesis药用蜀葵---影响内皮素ET-1Alcearosea---affectendothelin-1(ET-1)独行菜(Lepidiumapetalum)---通过IL-6下调MITFPeppergrass(Lepidiumapetalum)---downregulateMITFthroughIL-6应用----预防紫外线引起炎症性色斑Application----preventUV-inducedpostinflammatoryhyperpigmenation独行菜Peppergrass蜀葵Hollyhock(Alcearosea)甘草提取物(licoriceextract)•甘草黄酮-抗炎licoflavone-anti-inflamation•甘草黄苷-表皮更新epidermalturnover/renewal甘草Licorice加速表皮更新Accelerateturnoverrate/renewalsofepidermis•果酸（乳酸、苹果酸）Fruitacids(lacticacid,malicacid)•甘草黄苷（甘草）甘草黄苷(licorice)•亚油酸、亚麻酸linoleicacid、LinolenicAcid中药研究TraditionalChinesemedicineresearches•筛选:300种醇和水提取物Screening:alcoholandwatersolubleextractsof300kinds•单体---体外细胞试验Monomer---invitrocellculturetests18ɑ-甘草酸双胺盐、芦荟素、苦参碱、肉桂酸、淫羊藿苷、红景天甙、橙皮苷、表没食子儿茶素没食子酸酯18ɑ-Diammoniumglycyrrbizinate,Aloin,Ma