中国中药杂志

2021, v.46(02) 359-365

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

顾琦;朱学敏;魏旭超;梁莹;顾薇;陈军;
GU Qi;ZHU Xue-min;WEI Xu-chao;LIANG Ying;GU Wei;CHEN Jun;School of Pharmacy, Nanjing University of Chinese Medicine;Collaborative Innovation Center for Industrialization Process of Traditional Chinese Medicine Resources in Jiangsu Province;

摘要(Abstract):

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分布,并选取含量较高的成分采用分子模拟技术与角质脂质神经酰胺3进行分子对接,基于最佳构象计算相互作用能值。热性中药挥发油的皮肤细胞毒性显著高于温性中药挥发油,但两者的在体皮肤刺激性却没有显著差异,并且均远低于经典的化学促渗剂氮酮。GC-MS分析表明热性中药挥发油均含有倍半萜成分(33.56%±19.38%),而温性中药挥发油几乎不含倍半萜成分。与单萜成分相比,热性中药挥发油的倍半萜成分给药后易于驻留在皮肤角质层中形成贮库。分子模拟结果表明倍半萜类成分与神经酰胺3之间的结合能明显强于单萜成分(P<0.01)。倍半萜贮库效应可能是热性中药挥发油体内外皮肤毒性差异的主要机制,热性中药挥发油值得作为透皮促渗剂开发。
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.

关键词(KeyWords): 热性中药挥发油;温性中药挥发油;皮肤细胞毒性;皮肤刺激性;倍半萜贮库效应
hot essential oil;warm essential oil;skin cytotoxicity;skin irritation;sesquiterpene reservoir effect

Abstract:

Keywords:

基金项目(Foundation): 江苏省中药资源产业化过程协同创新中心重点项目(ZDXMHT-1-15)

作者(Authors): 顾琦;朱学敏;魏旭超;梁莹;顾薇;陈军;
GU Qi;ZHU Xue-min;WEI Xu-chao;LIANG Ying;GU Wei;CHEN Jun;School of Pharmacy, Nanjing University of Chinese Medicine;Collaborative Innovation Center for Industrialization Process of Traditional Chinese Medicine Resources in Jiangsu Province;

DOI: 10.19540/j.cnki.cjcmm.20201022.302

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