温热药性对中药挥发油透皮促渗剂皮肤毒性的影响及其机制研究

比较温热药性对中药挥发油透皮促渗剂体内外皮肤毒性的影响并探讨其作用机制.从温里药中选取4种热性中药(高良姜、干姜、吴茱萸、胡椒)和4种温性中药(花椒、丁香、小茴香、荜澄茄)提取挥发油,用人角质形成细胞评价皮肤细胞毒性;以局部给药后的病理评分结果为指标比较在体皮肤刺激性.分析热性中药挥发油成分及局部给药后在皮肤角质层内的...

Effect of hot or warm property on skin toxicity of essential oil as penetration enhancer and its mechanism

To compare the effect of hot or warm property of Chinese medicine(CM)on the skin toxicity of essential oils(EOs)as penetration enhancer in vitro and in vivo,and explore the mechanism.EOs were extracted from WIM of Bichengqie(Litseae Fructus),Dingxiang(Flos Syzygii Aromatici),Huajiao(Pericarpium Zanthoxyli Bungeani),and Xiaohuixiang(Fructus Foeniculi)with warm property,and Ganjiang(Rhizoma Zingiberis),Gaoliangjiang(Rhizoma Alpiniae Officinari),Hujiao(Fructus Piperis),and Wuzhuyu(Fructus Evodiae Rutaecarpae)with hot property,respectively.Then the in vitro toxicity was evaluated by human keratinocyte cytotoxicity.In vivo skin irritation potency was also evaluated through pathological observation after topical administration.The components,especially those located in stratum corneum,were analyzed by GC-MS.The main components,namely monoterpenes and sesquiterpenes,of EOs extracted from CM with hot property,were detected for the interaction with keratino-lipid ceramide 3 by molecular simulation technology;and the interaction energy value was calculated based on the optimal conformation.It was found that the skin cell toxicity of EOs from CM with hot property was significantly higher than that of EOs from CM with warm property.However,there was no significant difference between them by in vivo skin irritation evaluation.Whether from CM with hot property or warm property,EOs showed a significant reduced toxicity compared with azone.Sesquiterpenes(33.56%±19.38%)were found to be one of the main components in EOs from CM with hot property,while almost no sesquiterpenes was found in EOs from CM with warm property.After topical administration of EOs from CM with hot property,sesquiterpenes were demonstrated to be prone to locate in stratum corneum.The results of molecular simulation also revealed that the interaction between sesquiterpenes and ceramide 3 was significantly stronger than that of monoterpenes(P<0.01).In conclusion,the location of sesquiterpenes in stratum corneum resulted in the significant difference between in vitro skin cell toxicity and in vivo skin irritation potency.The EOs from CM with hot property shall be taken into account for further development of potent penetration enhancer.