摘要
目的采用网络药理学和体外研究探究瓜蒌薤白半夏汤治疗动脉粥样硬化的分子机制。方法从TCMSP数据库检索瓜蒌薤白半夏汤的所有化学成分及其靶点。以“Atherosclerosis”为检索词检索OMIM、DrugBank和TTD数据库,剔除重复选项,得到动脉粥样硬化的相关靶点;采用DAVID数据库对交集靶点进行GO和KEGG通路富集分析;最后在Ox-LDL诱导的人主动脉内皮细胞损伤模型上确证分析结果。结果共检索到瓜蒌薤白半夏汤的30个活性化合物分子及其治疗动脉粥样硬化的78个潜在靶点,靶点主要涉及炎症通路、细胞凋亡等。选择β-谷甾醇作为治疗动脉粥样硬化的潜在药效分子验证网络药理分析结果的正确性。体外研究表明,β-谷甾醇可阻止Ox-LDL诱导的人主动脉内皮细胞凋亡,明显降低细胞培养液中的IL^(-1)β、IL-6和TNF-α水平,以及细胞中p-NF-κB/NF-κB、IL^(-1)β、IL-6和TNF-α的蛋白表达量。结论瓜蒌薤白半夏汤可作用于多个靶点、多条通路,主要通过调控炎症、凋亡等通路而发挥治疗动脉粥样硬化作用。
Aim To explore the molecular mechanism of Gualou Xiebai Banxia decoction in the treatment of atherosclerosis by network pharmacology and in vitro study.Methods All chemical constituents and targets of Gualou Xiebai Banxia decoction were retrieved from TCMSP database.OMIM,DrugBank and TTD databases were searched with“atherosclerosis”as the search term,and the related targets of atherosclerosis were obtained after eliminating duplicate options.DAVID database was used for GO and KEGG pathway enrichment analysis of intersection targets.Finally,the analysis results were confirmed in the ox-LDL induced human aortic endothelial cell injury model.Results A total of 30 active compound molecules in Gualou Xiebai Banxia decoction and 78 potential targets for the treatment of atherosclerosis were retrieved.The therapeutic targets were mainly related to inflammatory pathway,apoptosis and so on.β-sitosterol was chosen as a potential pharmacodynamic molecule for the treatment of atherosclerosis to verify the correctness of the results of network pharmacological analysis.In vitro experiments showed that,β-sitosterol could prevent ox-LDL induced apoptosis of human aortic endothelial cells and significantly reduce the level of IL^(-1)β,IL-6 and TNF-αin cell culture medium,and protein expression of p-NF-κB/NF-κB,IL^(-1)β,IL-6 and TNF-αin cells.Conclusions The treatment effect of Gualou Xiebai Banxia decoction on atherosclerosis is mainly mediated by regulating inflammation,apoptosis and other pathways through multi-component effect,multiple targets and multiple pathways.
作者
冯利
庄安琪
李轶维
王月
杨科
FENG Li;ZHUANG An-qi;LI Yi-wei;WANG Yue;YANG Ke(School of Medicine, The Open University of China, Beijing 100039, China;School of Life Sciences, China Jiliang University, Hangzhou 310018, China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2022年第6期904-912,共9页
Chinese Pharmacological Bulletin
基金
国家自然科学基金青年项目(No 81803761)。
关键词
瓜蒌薤白半夏汤
动脉粥样硬化
网络药理学
内皮细胞
炎症通路
细胞凋亡
Gualou Xiebai Banxia decoction
atherosclerosis
network pharmacology
endothelial cells
inflammatory pathway
cell apoptosis