温里祛寒中药方剂抗寒活性成分筛选及药效学验证  

Screening of anti-cold active components from Wenli Quhan Chinese medicine prescriptions and pharmacodynamic verification

作　　者：卫贺 苗艳丰 张静 李照雪 王晓琴 张波 WEI He;MIAO Yanfeng;ZHANG Jing;LI Zhaoxue;WANG Xiaoqin;ZHANG Bo(School of Pharmacy,Shihezi University/Key Laboratory of Xinjiang Endemic Phytomedicine Resources,Ministry of Education,Shihezi,Xinjiang 832003,China;School of Pharmacy,Chengdu University/Sichuan Antimicrobial Industry Research Institute,Chengdu,Sichuan 610106,China)

机构地区：[1]石河子大学药学院/新疆植物药资源利用教育部重点实验室,新疆石河子832003 [2]成都大学药学院/四川抗菌素工业研究所,四川成都610106

出　　处：《石河子大学学报（自然科学版）》2023年第4期488-497,共10页Journal of Shihezi University(Natural Science)

基　　金：国家自然科学基金项目(U1603122);新疆生产建设兵团创新领域中青年领军人才项目(2018CB019);四川省天府峨眉创新领军人才项目(1811)。

摘　　要：目的基于中医“治寒以热”辨证理论和温里祛寒方剂温中散寒的功效,对温里祛寒方中抗寒活性成分筛选并进行体外药效学验证。方法基于大数据分析温里祛寒方剂药材分布特性;通过系统药理学方法进行活性成分的虚拟筛选和关键靶点的富集分析。建立体外BCPAP细胞低温联合缺氧模型,通过代表成分的细胞活力及调控活性氧水平、抗凋亡/坏死情况进行体外药效学验证。结果共收集到温里祛寒方剂147方,涉及中药材153味,药性主要为温/热、辛/苦,归脾肾肝经,具有生热、发散风寒之功效;药材中的化学成分主要参与细胞对外界物质及环境刺激的反应、体温调节等生物过程和HIF-1信号通路、细胞凋亡、甲状腺激素合成等信号通路的调节。体外药效学结果显示,代表成分阿魏酸、姜黄素、肉桂醛、6-姜酚、甘草苷能够有效抑制低温联合缺氧诱导BCPAP细胞活力的降低,改善细胞氧化应激水平和凋亡/坏死情况(P<0.05)。分子对接结果显示活性成分与关键蛋白具有良好的结合活性(结合能<-5.0 kcal·mol^(-1))。结论温里祛寒方剂及其活性成分能够帮助机体应对低温刺激,其抗寒作用与改善包括甲状腺在内的神经内分泌系统损伤相关。Objective Based on the syndrome differentiation theory of"treating cold by heat"in Traditional Chinese Medicine(TCM)and the efficacy of warming interior for dispelling cold of Wenli Quhan Prescriptions,to screen the anti-cold active ingredients in traditional Wenli Quhan Prescriptions and conduct the in vitro pharmacodynamic verification.Methods Based on big data,the distribution characteristics of medicinal materials in Wenli Quhan Prescriptions were analyzed.The virtual screening of active ingredients and enrichment analysis of key targets were performed by systematic pharmacology.The BCPAP cell model of low temperature combined with hypoxia was established in vitro,and pharmacodynamic verification was performed through the effect of representative components on cell viability and regulation of reactive oxygen species and anti-apoptosis/necrosis levels.Results A total of 147 Wenli Quhan Prescriptions were collected,involving 153 Chinese herbal materials.The herbal properties are mainly warm and hot,pungent and bitter,which mainly enter the spleen meridian,kidney meridian and liver meridian,and had the effects of generating heat and dispersing it.The chemical components in high-frequency herbal materials are mainly involved in the cellular responses to external substances and environmental stimuli,temperature regulation and other biological processes,and the regulation of HIF-1 signaling pathway,apoptosis,thyroid hormone synthesis and other signaling pathways.In vitro pharmacodynamic evaluation results showed that ferulic acid,curcumin,cinnamaldehyde,6-gingerol,and liquiritin could effectively inhibit the decrease in cell viability of BCPAP induced by low-temperature combined with hypoxia(P<0.05),and reduce the cell oxidative stress and apoptosis/necrosis level.Molecular docking results showed that the active components had a good binding activity with key proteins(Binding Energy<-5.0 kcal·mol^(-1)).Conclusion Wenli Quhan Prescriptions and their active components can help the body to cope with low-temperature s

关 键 词：温里祛寒方剂 大数据 成药性评价 抗寒 缺氧损伤 BCPAP细胞 分子对接 

分 类 号：R285.1[医药卫生—中药学]