基于网络药理学和分子对接的当归六黄汤治疗围绝经期综合征作用机制研究

目的 采用网络药理学和分子对接技术研究当归六黄汤治疗围绝经期综合征（PMS）的作用机制。方法 利用中药系统药理学数据库与分析平台（TCMSP）和UniProt数据库检索当归六黄汤的活性成分和相应的靶点。基于GeneCards、DrugBank、OMIM数据库获取与PMS相关的靶点，并得到当归六黄汤与PMS的交集靶点。构建当归六黄汤活性成分-交集靶点相互作用网络。利用STRING在线数据库进行蛋白质-蛋白质相互作用（PPI）分析，筛选核心靶点。采用Metascape在线数据库进行基因本体（GO）功能注释及京都基因与基因组百科全书（KEGG）通路富集。通过Discovery Studio 2016进行分子对接，确定关键活性成分与核心靶点相互作用的分子基础。结果 共获取当归六黄汤112个活性成分，经筛选得到5个关键活性成分，分别为槲皮素、豆甾醇、β-谷甾醇、山柰酚、7-O-甲基-异微凸剑叶莎醇，主要发挥抗炎和雌激素样作用。获取当归六黄汤与PMS的交集靶点52个，经筛选得到5个核心靶点，分别是白细胞介素-6（IL-6）、前列腺素G/H合酶2（PTGS2）、雌激素受体1（ESR1）、IL-1B和糖皮质激素受体基因亚科3 C组成员1（NR3C1），主要参与炎症反应和激素调节。KEGG富集分析显示，当归六黄汤治疗PMS主要通过化学致癌-受体激活、脂质和动脉粥样硬化、癌症、神经活性配体-受体相互作用、流体剪切应力和动脉粥样硬化、5-羟色胺能突触、雌激素信号通路、突触小泡循环、腺苷酸依赖的蛋白激酶（AMPK）信号通路等发挥作用。分子对接结果验证了当归六黄汤的关键活性成分可以与核心靶点蛋白形成稳定的对接模型。结论 基于网络药理学和分子对接技术，筛选出当归六黄汤治疗PMS的关键活性成分、核心靶点和主要信号通路，为当归六黄汤治疗PMS提供了参考。

Mechanism of Danggui Liuhuang Decoction in the Treatment of Perimenopausal Syndrome Based on Network Pharmacology and Molecular Docking

Objective To study the mechanism of Danggui Liuhuang Decoction (DGLHD) in the treatment of perimenopausal syndrome (PMS) via network pharmacology and molecular docking.Methods The active ingredients and corresponding targets of DGLHD were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and UniProt. The PMS-related targets were obtained from GeneCards, DrugBank, and OMIM. The common targets shared by DGLHD and PMS were identified. The DGLHD active ingredient-common target network was constructed. The protein-protein interaction (PPI) was predicted via STRING online to screen out the core targets. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed with Metascape. Molecular docking was simulated in Discovery Studio 2016 to determine the molecular basis for the interaction of key active ingredients with core targets.Results A total of 112 active ingredients of DGLHD were obtained. Five key active ingredients were screened out, including quercetin, stigmasterol, beta-sitosterol, kaempferol, and 7-O-methylisomucronulatol, which mainly exerted anti-inflammatory and estrogen-like effects. DGLHD and PMS shared 52 common targets, among which 5 core targets were screened out, including interleukin-6 (IL-6), prostaglandin-endoperoxide synthase 2 (PTGS2), estrogen receptor 1 (ESR1), IL-1B, and nuclear receptor subfamily 3, group C, member 1 (NR3C1). The core targets were mainly involved in inflammatory response and hormone regulation. KEGG enrichment analysis predicted that DGLHD treated PMS mainly through chemical carcinogenesis-receptor activation, lipid and atherosclerosis, pathways in cancer, neuroactive ligand-receptor interaction, fluid shear stress and atherosclerosis, serotonergic synapse, estrogen signaling pathway, synaptic vesicle cycle, and adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. The molecular docking results verified that the key active components of DGLHD can form a stable docking model with the core targets.Conclusion The key active components, core targets, and main signaling pathways of DGLHD in the treatment of PMS were screened out via network pharmacology and molecular docking, which provided a theoretical basis for the application of DGLHD in the treatment of PMS.