植物皮肤脱色剂的研究进展

1、植物皮肤脱色剂的研究进展美与白肤色决定因素 皮肤内色素 Pigments in skin 黑素 Melanin 类胡萝卜素 Carotenoid 血红蛋白比例 Ratio of hemoglobin 皮肤厚薄 Thickness of skin 表皮 Epidermis 真皮 Dermis 表皮黑素细胞的原子力显微镜观察矛 盾化学剂-天然植物 汞剂Mercurials 氢醌Hydroquinone 糖皮质激素Glucocorticoids 效果好，安全性差Good in efficacy，but bad in safety研究流程 1.植物筛选 Plant screening 酪氨酸活性测定-

2、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Tyrosinase activity measurement-mushroom tyrosinase and human tyrosinase Dopa melanin auto oxidation and melanin formation measurement 2.有效性安全性验证 Efficacy and safety tests 黑素瘤细胞培养 Melanoma cell culture 人表皮黑素细胞培养 Human melanocytes culture 豚鼠皮肤试验 Guinea pig skin test 人临床效果观察

3、 Human clinical study and observation 3.活性基团，开发新药 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 5，6-二羟吲哚 5，6-二羟吲哚-2-羧酸 ( DHI) (DHICA) TRP-1 DHI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 直接或间接抑制酪氨酸酶 Direct or indirect inhibition effe

4、ct on tyrosinase 还原剂和活性氧族Reducing reagent and reactive oxygen species 降解酪氨酸酶 Tyrosinase degradation 抑制黑素体转运 Inhibition of melanosome transportation 抑制炎症引起的合成黑素反应Inhibition of inflammation induced melanin synthesis 加速表皮更新Accelerate turnover rate of epidermis直接或间接抑制酪氨酸酶 熊果苷熊果苷Arbutin (熊果、沙梨树叶) (Arctos

5、taphylos uva-ursi L. Spreng; P.pyrifolia (Burm.)Nakai tree leaves) 芦荟苦素芦荟苦素Aloesin (芦荟, Aloe) 甲酯龙胆酸甲酯龙胆酸 2, 5-Methyl hydroxybenzoic acid (Gentisic methyl) (龙胆) (Gentiana scabra Bge) 生物类黄酮生物类黄酮 Bioflavonoid 山奈酚（银杏）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: 黑素瘤细胞Melanoma 人黑素细胞Human melanocytes 动物模型Animal models 人体临床试验Human clinical study熊果Arctostaphylos uva-ursi L. Spreng熊果苷 熊果苷-(Arbutin) Alpha-熊果苷-(Alpha-arbutin)

7、 脱氧熊果苷-(Deoxy arbutin)芦荟苦素(aloesin) 竞争性抑制多巴氧化Competetively inhibit on dopa oxidation 非竞争性抑制酪氨酸酶羟化Non-competetively inhibit tyrosinase hydroxidation龙胆酯酸 草原龙胆Eustoma ressellianum2, 5-Methyl hydroxybenzoic acid (Gentisic methyl) 有效-选择性抑制酪氨酸酶,可能和铜离子鳌合相关In effect-Selectively inhibit tyrosinase and may ch

8、elate with copper ions 安全-减轻氢醌的细胞毒性 对哺乳动物细胞无致畸性Safe-Reduce cytotoxicity by hydroquinone and no teratogenicity on mammalian cells生物类黄酮(bioflavonoid)银杏Gingko(Ginkgo biloba L.) 金银花Honeysuckle(Lonicera japonicaThunb) 芸香科豆科伞形科银杏科菊科Rutaceae Leguminosae Umbelliferae Ginkgoaceae Asteraceae 黄酮醇-螯合铜离子，竞争性抑制酪氨

9、酸酶活性 Flavonol-Chelate copper ions and competetively inhibit tyrosinase activity 黄酮-非竞争性抑制酪氨酸酶活性 Flavone-Non-competetively inhibit tyrosinase activity 异黄酮-效果差Isoflavone-Do not have good effect兼有清除自由基的酪氨酸酶抑制剂 多酚类Polyphenols 鞣花酸（石榴皮）Ellagic acid (megranate skin) 白藜芦醇（葡萄酒）Resveratrol (Wine) 茶多酚（绿茶）Tea p

10、olyphenol (Green tea)原花青素（葡萄籽）Procyanidins (Grape seed) 桑辛素F（桑科）Moracin F (Moraceae)鞣花酸(ellagic acid) 非竞争性抑制酪氨酸酶Non-competetively inhibit tyrosinase activity 清除氧自由基Eliminate oxidative free radicals 豚鼠试验Guinea pig study石榴Megranate白藜芦醇(Resveratrol)竞争性抑制Competetive inhibition桑树Mulberry-氧化白藜芦醇(oxyresver

11、atrol)更强抑制DOPA 氧化话性oxyresveratrol have stronger inhibition effect on DOPA oxidative activity虎杖Polygonum cuspidatum Sieb 茶多酚 绿茶 Green tea 表没食子儿茶素没食子酸酯（EGCG)(-)-epigallocatechin-3-gallate (EGCG)绿茶Green tea其它多酚 原花青素 Procyanidins构树(paper mulberry)桑白 桑科树根皮提纯-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构树Papermulberry Broussonetia papyrifera (Linn.)Vent. 还原剂和活性氧族 生育酚（植物油、坚果、日本山椒）-tocopherols (vegetable oils, nuts, Zanthoxylum Japonica) 抑制黑素细胞膜脂质过氧化反应 Inhibition on melanocyte lipid membrane peroxidation 降解酪氨酸酶 不饱和脂肪酸Unsaturated fatt

13、y acids激活酪氨酸酶降解酶Activation on degradation enzymes of tyrosinase抑制黑素体转运 大豆大豆Soybean：两种丝氨酸蛋白酶抑制剂两种丝氨酸蛋白酶抑制剂 Two kinds of serine protease inhibitors Bowman-Birk胰蛋白酶抑制剂(BBI) Bowman-Birk trypsin inhibitor (BBI) 大豆胰蛋白酶抑制剂大豆胰蛋白酶抑制剂(STI)Soybean trypsin inhibitor (STI)干扰蛋白酶活化受体干扰蛋白酶活化受体-2途径途径 Interfere with

14、protease activated receptor-2 (PAR-2) pathway 烟酰胺(niacinamide) 抑制黑素体转运Inhibition on melanosome transportation 抗糖基化Anti-advanced glycation 抑制炎症引起的合成黑素反应 药用蜀葵-影响内皮素ET-1 Alcea rosea -affectendothelin-1(ET-1) 独行菜(Lepidium apetalum)-通过IL-6下调MITF Peppergrass (Lepidiumapetalum)-downregulate MITF through IL

15、-6 应用-预防紫外线引起炎症性色斑Application-prevent UV- induced post inflammatory hyperpigmenation独行菜Peppergrass 蜀葵Hollyhock (Alcea rosea) 甘草提取物(licorice extract) 甘草黄酮-抗炎licoflavone - anti-inflamation 甘草黄苷-表皮更新epidermal turnover/renewal甘草Licorice加速表皮更新 果酸（乳酸、 苹果酸）Fruit acids (lactic acid, malic acid) 甘草黄苷（甘草）甘草黄苷

16、 (licorice) 亚油酸、亚麻酸linoleic acid、Linolenic Acid 中药研究 筛选筛选: 300种醇和水提取物种醇和水提取物 Screening: alcohol and water soluble extracts of 300 kinds单体单体-体外细胞试验体外细胞试验 Monomer-in vitro cell culture tests 18-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18-Diammonium glycyrrbizinate, Aloin, Matrine, Cinnamic acid, Icariin,Ica, Salidroside, Hesperidin,EGCG豚鼠试验豚鼠试验 Guinea pig tests 橙皮苷、甘草素、甘草酸双胺