摘要
目的探究化痰药与祛湿药治疗肥胖型多囊卵巢综合征(PCOS)机制的异同并寻找关键活性成分。方法利用HERB数据库筛选化痰药及祛湿药成分及靶点,运用欧易云平台对靶点进行基因本体及京都基因与基因组百科全书富集分析,利用Cytoscape 3.8.0软件构建通路网络图以显示通路差异。利用基因表达汇编数据库通过R 4.2.2软件筛选PCOS关键靶点,采用分子对接技术对关键活性成分与靶点的对接能力进行预测,并结合分子动力学模拟实验验证对接效能。结果化痰药与祛湿药共有活性成分52种,共有靶点81个;两者共有通路涉及脂质调控、胰岛素调节、激素调节、促进卵母细胞成熟等多个角度,与肥胖型PCOS病理机制相符。化痰药在调节激素及胰岛素方面作用更为突出,而祛湿药则在维生素代谢及抗炎角度效果更为优异。槲皮素、β-谷甾醇及豆甾醇确定为关键活性成分,其中豆甾醇与PCOS关键靶点丘奇尔结构域蛋白1(CHURC1)及肿瘤坏死因子配体超家族成员11(TNFSF11)结合最为优异,分子动力学模拟进一步证明了β-谷甾醇与TNFSF11结合的强稳定性。结论初步探析了化痰药与祛湿药治疗肥胖型PCOS的潜在靶点与机制,对寻找关键的活性成分及指导临床应用具有一定指导意义。
Objective To investigate the similarities and differences in the mechanisms of Huatan drugs and Qushi drugs in treating obesity-related polycystic ovary syndrome(PCOS)and to identify the key active components.Methods Components and targets of Huatan drugs and Qushi drugs were screened by HERB database.The OmicsCloud platform was employed for enrichment analyses of targets by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes.Pathway networks were constructed by Cytoscape 3.8.0 software to visualize pathway differences.PCOS-related key targets were identified by Gene Expression Omnibus database and R 4.2.2 software.Molecular docking techniques were used to predict binding affinities between the key components and targets,followed by validation through molecular dynamics simulations.Results Huatan drugs and Qushi drugs shared 52 active components and 81 targets.Common pathways involved lipid metabolism,insulin regulation,hormonal regulation,and oocyte maturation,aligning with the pathological mechanisms of obesity-related PCOS.Huatan drugs exhibited superior efficacy in hormonal and insulin regulation,while Qushi drugs excelled in vitamin metabolism and anti-inflammatory pathways.Quercetin,β-sitosterol,and stigmasterol were identified as key components.Stigmasterol demonstrated optimal binding with PCOS-associated key targets Churchill domain-containing protein 1(CHURC1)and tumor necrosis factor ligand superfamily member 11(TNFSF11),while molecular dynamics simulations confirmed the robust stability ofβ-sitosterol and TNFSF11 binding.Conclusion This study elucidates potential targets and mechanisms of Huatan drugs and Qushi drugs in treating obesity-related PCOS,providing insights for identifying key active components and guiding clinical application.
作者
丁杰
松迪
俞瑾
俞超芹
DING Jie;SONG Di;YU Jin;YU Chaoqin(Department of Traditional Chinese Medicine(Gynecology),The First Affiliated Hospital of Naval Medical University(Second Military Medical University),Shanghai 200433,China;Department of Reproductive Medicine,The First Affiliated Hospital of Naval Medical University(Second Military Medical University),Shanghai 200433,China)
出处
《海军军医大学学报》
北大核心
2025年第8期1018-1026,共9页
Academic Journal of Naval Medical University
基金
国家自然科学基金(81973896,82004408).
关键词
多囊卵巢综合征
肥胖
化痰药
祛湿药
分子机制
polycystic ovary syndrome
obesity
Huatan drugs
Qushi drugs
molecular mechanism
