文献类型：期刊文献

中文题名：祖师麻皮肤刺激性观察和基于生物信息学的机制预测

英文题名：Skin Irritation of Zushima and Prediction of Its Mechanism Based on Bioinformatics

作者：赵苗苗[1];马骏[1,2];孙涛[1];朱仁愿[3];刘兴国[3];田悦[1];毛著鸿[4];段海婧[1];魏舒畅[1]

第一作者：赵苗苗

机构：[1]甘肃中医药大学,兰州730000;[2]国家中医药管理局中医药科研三级实验室中药药理实验室,兰州730000;[3]兰州市食品药品检验检测研究院,兰州730020;[4]甘肃泰康制药有限责任公司,武威733000

第一机构：甘肃中医药大学

年份：2024

卷号：19

期号：2

起止页码：147

中文期刊名：世界中医药

外文期刊名：World Chinese Medicine

收录：CSTPCD;;北大核心:【北大核心2023】；

基金：国家自然科学基金项目(82060721);甘肃省药品产业技术扶持项目(2019KF001)。

语种：中文

中文关键词：祖师麻;萃取部位;皮肤刺激性;生物信息学;瑞香毒素;木犀草素;大黄素甲醚;网络药理学

外文关键词：Zushima;Extraction parts;Skin irritation;Bioinformatics;Daphnetoxin;Luteolin;Physcion;Network pharmacology

摘要：目的:观察祖师麻干浸膏粉及不同萃取部位的皮肤刺激性,并基于生物信息学预测其刺激性成分及作用机制。方法:将斯泼累格·多雷(SD)大鼠随机分为完整皮肤组和破损皮肤组,观察连续给药7 d和停药后3 d皮肤状况。运用中药系统药理学数据库与分析平台(TCMSP)查询祖师麻刺激性成分和作用靶点。通过GeneCards数据库、在线人类孟德尔遗传数据库(OMIM)等数据库收集疾病靶点。运用Metascape平台进行基因本体(GO)富集以及京都基因和基因组百科全书(KEGG)富集分析,将核心靶点与祖师麻刺激性成分进行分子对接。结果:祖师麻干浸膏粉低、中剂量组对破损皮肤有轻微红斑、水肿反应;祖师麻干浸膏粉高剂量组、石油醚部位和二氯甲烷部位对完整皮肤和破损皮肤均有轻微红斑、水肿反应;乙酸乙酯部位和水层部位均无红斑、水肿反应。2)从祖师麻活性成分中筛选出7种刺激性成分,通路富集的主要通路为磷酸肌醇-3-激酶/蛋白激酶B(PI3K-AKT)信号通路、细胞增殖的肉瘤基因(Ras)信号通路、促分裂原活化的蛋白激酶(MAPK)信号通路、端粒结合蛋白(Rap1)信号通路和松弛素(Relaxin)信号通路等。分子对接结果中瑞香毒素、木犀草素以及大黄素甲醚与核心靶点的结合最稳定。结论:祖师麻干浸膏粉高剂量下有轻微皮肤刺激性,可能是存在于石油醚和二氯甲烷部位中的瑞香毒素、木犀草素以及大黄素甲醚等通过多靶点、多通路的复杂作用促进炎症介质的生成,引起皮肤轻微红斑和水肿。
Objective:To Observe the skin irritation of dried extract powder and different extraction parts of Zushima,and predict its irritant components and mechanism of action based on bioinformatics.Methods:SD rats were randomly divided into integral skin group and broken skin group.The skin condition was observed 7 days after drug administration and 3 days after drug withdrawal.The TCMSP were used to query the irritant components and targets of Zushima.Disease targets were collected through GeneCards,OMIM and other databases.Metascape platform was used for GO enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis.The core targets and the stimulating components of Zushima were used for molecular docking.Results:The low-dose group and medium-dose group of Dried Zushima extract powder had slight erythema and edema on broken skin.The high-dose group of Dried Zushima extract powder,petroleum ether parts and dichloromethane parts had slight erythema and edema reaction on integral skin and broken skin.There was no erythema and edema reaction on integral skin and broken skin in ethyl acetate and water layer parts.Seven irritant components were screened from the active ingredients of Zushima,which were mainly enriched in PI3K-AKT,Ras,MAPK,Rap1 and Relaxin signaling pathways,and so on.Molecular docking results showed that the key targets formed stable structures with active components Daphnetoxin,Luteolin and Physcion.Conclusion:The high-dose of Dried Zushima extract powder has slight skin irritation,which may be due to the complex effects of the Daphnetoxin,luteolin and Physcion in petroleum ether and dichloromethane to promote the generation of inflammatory factors through multi-target and multi-pathway,causing slight erythema and edema of the skin.