植物皮膚脫色劑的研究進(jìn)展

1、植物皮膚脫色劑的研究進(jìn)展美與白膚色決定因素 皮膚內(nèi)色素 Pigments in skin 黑素 Melanin 類(lèi)胡蘿卜素 Carotenoid 血紅蛋白比例 Ratio of hemoglobin 皮膚厚薄 Thickness of skin 表皮 Epidermis 真皮 Dermis 表皮黑素細(xì)胞的原子力顯微鏡觀(guān)察矛 盾化學(xué)劑-天然植物 汞劑Mercurials 氫醌Hydroquinone 糖皮質(zhì)激素Glucocorticoids 效果好，安全性差Good in efficacy，but bad in safety研究流程 1.植物篩選 Plant screening 酪氨酸活性測(cè)定-

2、蘑菇酪氨酸酶、人酪氨酸酶 多巴色素自動(dòng)氧化生成黑素測(cè)定Tyrosinase activity measurement-mushroom tyrosinase and human tyrosinase Dopa melanin auto oxidation and melanin formation measurement 2.有效性安全性驗(yàn)證 Efficacy and safety tests 黑素瘤細(xì)胞培養(yǎng) Melanoma cell culture 人表皮黑素細(xì)胞培養(yǎng) Human melanocytes culture 豚鼠皮膚試驗(yàn) Guinea pig skin test 人臨床效果觀(guān)察

3、 Human clinical study and observation 3.活性基團(tuán)，開(kāi)發(fā)新藥 Active groups and new drug development酪氨酸 多巴 酪氨酸酶酪氨酸酶 多巴醌 谷胱甘肽 or半胱氨酸 多巴色素 半胱氨酰多巴 TRP-2 5，6-二羥吲哚 5，6-二羥吲哚-2-羧酸 ( DHI) (DHICA) TRP-1 DHI多聚體 DHICA多聚體 優(yōu)黑素 褐黑素 TRP-1 （多巴色素互變異構(gòu)酶） TRP-2（5，6-二羥吲哚-2-羥酸聚合酶 ） 主要機(jī)制 直接或間接抑制酪氨酸酶 Direct or indirect inhibition effe

4、ct on tyrosinase 還原劑和活性氧族Reducing reagent and reactive oxygen species 降解酪氨酸酶 Tyrosinase degradation 抑制黑素體轉(zhuǎn)運(yùn) Inhibition of melanosome transportation 抑制炎癥引起的合成黑素反應(yīng)Inhibition of inflammation induced melanin synthesis 加速表皮更新Accelerate turnover rate of epidermis直接或間接抑制酪氨酸酶 熊果苷熊果苷Arbutin (熊果、沙梨樹(shù)葉) (Arctos

5、taphylos uva-ursi L. Spreng; P.pyrifolia (Burm.)Nakai tree leaves) 蘆薈苦素蘆薈苦素Aloesin (蘆薈, Aloe) 甲酯龍膽酸甲酯龍膽酸 2, 5-Methyl hydroxybenzoic acid (Gentisic methyl) (龍膽) (Gentiana scabra Bge) 生物類(lèi)黃酮生物類(lèi)黃酮 Bioflavonoid 山奈酚（銀杏）Kaempferol (Gingko) 芹菜素（芹菜）Oleanolic Acid/Apigenin (Celery)柚皮素（柚）Naringenin (Citrus gra

6、ndis L. Osbeck ) 熊果苷(arbutin) 抑制酪氨酸酶活性抑制酪氨酸酶活性 Inhibition of tyrosinase activity 抑制抑制TRP-2活性活性 Inhibition on TRP-2 activity 有效性有效性 Efficacy: 黑素瘤細(xì)胞Melanoma 人黑素細(xì)胞Human melanocytes 動(dòng)物模型Animal models 人體臨床試驗(yàn)Human clinical study熊果Arctostaphylos uva-ursi L. Spreng熊果苷 熊果苷-(Arbutin) Alpha-熊果苷-(Alpha-arbutin)

7、 脫氧熊果苷-(Deoxy arbutin)蘆薈苦素(aloesin) 競(jìng)爭(zhēng)性抑制多巴氧化Competetively inhibit on dopa oxidation 非競(jìng)爭(zhēng)性抑制酪氨酸酶羥化Non-competetively inhibit tyrosinase hydroxidation龍膽酯酸 草原龍膽Eustoma ressellianum2, 5-Methyl hydroxybenzoic acid (Gentisic methyl) 有效-選擇性抑制酪氨酸酶,可能和銅離子鰲合相關(guān)In effect-Selectively inhibit tyrosinase and may ch

8、elate with copper ions 安全-減輕氫醌的細(xì)胞毒性 對(duì)哺乳動(dòng)物細(xì)胞無(wú)致畸性Safe-Reduce cytotoxicity by hydroquinone and no teratogenicity on mammalian cells生物類(lèi)黃酮(bioflavonoid)銀杏Gingko(Ginkgo biloba L.) 金銀花Honeysuckle(Lonicera japonicaThunb) 蕓香科豆科傘形科銀杏科菊科Rutaceae Leguminosae Umbelliferae Ginkgoaceae Asteraceae 黃酮醇-螯合銅離子，競(jìng)爭(zhēng)性抑制酪氨

9、酸酶活性 Flavonol-Chelate copper ions and competetively inhibit tyrosinase activity 黃酮-非競(jìng)爭(zhēng)性抑制酪氨酸酶活性 Flavone-Non-competetively inhibit tyrosinase activity 異黃酮-效果差I(lǐng)soflavone-Do not have good effect兼有清除自由基的酪氨酸酶抑制劑 多酚類(lèi)Polyphenols 鞣花酸（石榴皮）Ellagic acid (megranate skin) 白藜蘆醇（葡萄酒）Resveratrol (Wine) 茶多酚（綠茶）Tea p

10、olyphenol (Green tea)原花青素（葡萄籽）Procyanidins (Grape seed) 桑辛素F（?？疲㎝oracin F (Moraceae)鞣花酸(ellagic acid) 非競(jìng)爭(zhēng)性抑制酪氨酸酶Non-competetively inhibit tyrosinase activity 清除氧自由基Eliminate oxidative free radicals 豚鼠試驗(yàn)Guinea pig study石榴Megranate白藜蘆醇(Resveratrol)競(jìng)爭(zhēng)性抑制Competetive inhibition桑樹(shù)Mulberry-氧化白藜蘆醇(oxyresver

11、atrol)更強(qiáng)抑制DOPA 氧化話(huà)性oxyresveratrol have stronger inhibition effect on DOPA oxidative activity虎杖Polygonum cuspidatum Sieb 茶多酚 綠茶 Green tea 表沒(méi)食子兒茶素沒(méi)食子酸酯（EGCG)(-)-epigallocatechin-3-gallate (EGCG)綠茶Green tea其它多酚 原花青素 Procyanidins構(gòu)樹(shù)(paper mulberry)桑白 ?？茦?shù)根皮提純-桑辛素F抑制酪氨酸酶Moraceae tree roots and skin extract

12、s-Moracin F Inhibition of tyrosinase 清除氧自由基 Eliminate free radicals構(gòu)樹(shù)Papermulberry Broussonetia papyrifera (Linn.)Vent. 還原劑和活性氧族 生育酚（植物油、堅(jiān)果、日本山椒）-tocopherols (vegetable oils, nuts, Zanthoxylum Japonica) 抑制黑素細(xì)胞膜脂質(zhì)過(guò)氧化反應(yīng) Inhibition on melanocyte lipid membrane peroxidation 降解酪氨酸酶 不飽和脂肪酸Unsaturated fatt

13、y acids激活酪氨酸酶降解酶Activation on degradation enzymes of tyrosinase抑制黑素體轉(zhuǎn)運(yùn) 大豆大豆Soybean：兩種絲氨酸蛋白酶抑制劑兩種絲氨酸蛋白酶抑制劑 Two kinds of serine protease inhibitors Bowman-Birk胰蛋白酶抑制劑(BBI) Bowman-Birk trypsin inhibitor (BBI) 大豆胰蛋白酶抑制劑大豆胰蛋白酶抑制劑(STI)Soybean trypsin inhibitor (STI)干擾蛋白酶活化受體干擾蛋白酶活化受體-2途徑途徑 Interfere with

14、protease activated receptor-2 (PAR-2) pathway 煙酰胺(niacinamide) 抑制黑素體轉(zhuǎn)運(yùn)Inhibition on melanosome transportation 抗糖基化Anti-advanced glycation 抑制炎癥引起的合成黑素反應(yīng) 藥用蜀葵-影響內(nèi)皮素ET-1 Alcea rosea -affectendothelin-1(ET-1) 獨(dú)行菜(Lepidium apetalum)-通過(guò)IL-6下調(diào)MITF Peppergrass (Lepidiumapetalum)-downregulate MITF through IL

15、-6 應(yīng)用-預(yù)防紫外線(xiàn)引起炎癥性色斑Application-prevent UV- induced post inflammatory hyperpigmenation獨(dú)行菜Peppergrass 蜀葵Hollyhock (Alcea rosea) 甘草提取物(licorice extract) 甘草黃酮-抗炎licoflavone - anti-inflamation 甘草黃苷-表皮更新epidermal turnover/renewal甘草Licorice加速表皮更新 果酸（乳酸、 蘋(píng)果酸）Fruit acids (lactic acid, malic acid) 甘草黃苷（甘草）甘草黃苷

16、 (licorice) 亞油酸、亞麻酸linoleic acid、Linolenic Acid 中藥研究 篩選篩選: 300種醇和水提取物種醇和水提取物 Screening: alcohol and water soluble extracts of 300 kinds單體單體-體外細(xì)胞試驗(yàn)體外細(xì)胞試驗(yàn) Monomer-in vitro cell culture tests 18-甘草酸雙胺鹽、蘆薈素、苦參堿、肉桂酸、淫羊藿苷、紅景天甙、橙皮苷、表沒(méi)食子兒茶素沒(méi)食子酸酯18-Diammonium glycyrrbizinate, Aloin, Matrine, Cinnamic acid, Icariin,Ica, Salidroside, Hesperidin,EGCG豚鼠試驗(yàn)豚鼠試驗(yàn) Guinea pig tests 橙皮苷、甘草素、甘草酸雙胺