Zhang Q, Zhang M, Liu Y, Wang Y, Lv F, Wang Y
Department of Traditional Chinese Medicine, Sixth Medical Center, General Hospital of the Chinese People's Liberation Army, Beijing 100048, China.
Telemedicine Unit, Medical Security Centre, General Hospital of the Chinese People's Liberation Army, Beijing 100853, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2023 Sep 20;43(9):1536-1547. doi: 10.12122/j.issn.1673-4254.2023.09.11.
To explore the therapeutic mechanism of decoction (LWSZD) for perimenopausal insomnia (PI) based on network pharmacology.
TCMSP and Batman-TCM databases were searched for the active ingredients and targets of LWSZD and a herb-active ingredient-target network was constructed, and the disease targets were obtained from the OMIM, Genecards and Gene databases.The common targets were imported into STRING database and Cytoscape software to screen the core therapeutic targets, and GO enrichment and KEGG pathway analyses were performed using DAVID database.Molecular docking of the main active ingredients of LWSZD and the core targets was conducted using AutoDock, and the results were verified by observing the therapeutic effects of LWSZD and zolpidem in a rat model of PI induced by bilateral ovariectomy and intraperitoneal p-chlorophenylalanine injection.
A total of 99 active ingredients, 389 drug targets, 187 PI-related targets, and 15 drug-PI common targets were screened.The core active ingredients were armepavine, sanjoinenine and mairin, and the core targets included ESR1, SIRT1, SERPINE1, COMT and CCL2, which were involved in the positive regulation of transcription from RNA polymerase II promoter, signal transduction, response to drug and positive regulation of transcription and in the pathways of dopaminergic synapses, tyrosine metabolism and tryptophan metabolism.Molecular docking results showed that LWSZD had a strong binding with ESR1, SIRT1 and SERPINE1 and was comparable to zolpidem.In the rat models of PI, treatment with LWSZD effectively alleviated the symptoms of insomnia (<0.01), improved the levels of estrogen and other HPO axis-related hormones (<0.05), and promoted the mRNA and protein expressions of ESR1 and SIRT1 in the hypothalamus tissues (<0.01).
The active ingredients armepavine, sanjoinenine and mairin in LWSZD may synergistically regulate the expressions of ESR1, SIRT1 and SERPINE1 to improve PI in rats.
基于网络药理学探讨六味酸枣仁汤（LWSZD）治疗围绝经期失眠（PI）的作用机制。
通过中药系统药理学数据库与分析平台（TCMSP）和中药系统药理学研究平台（Batman-TCM）数据库检索LWSZD的活性成分及靶点，构建“药物-活性成分-靶点”网络，并从人类孟德尔遗传数据库（OMIM）、基因卡片数据库（Genecards）和基因数据库获取疾病靶点。将共同靶点导入STRING数据库和Cytoscape软件筛选核心治疗靶点，利用DAVID数据库进行基因本体（GO）富集分析和京都基因与基因组百科全书（KEGG）通路分析。采用AutoDock对LWSZD主要活性成分与核心靶点进行分子对接，并通过观察LWSZD与唑吡坦对双侧卵巢切除联合腹腔注射对氯苯丙氨酸诱导的PI大鼠模型的治疗效果进行验证。
共筛选出99个活性成分、389个药物靶点、187个PI相关靶点和15个药物-PI共同靶点。核心活性成分有阿朴啡、山茱萸宁碱和迈灵碱，核心靶点包括雌激素受体1（ESR1）、沉默信息调节因子1（SIRT1）、丝氨酸蛋白酶抑制剂E1（SERPINE1）、儿茶酚-O-甲基转移酶（COMT）和趋化因子配体2（CCL2），这些靶点参与RNA聚合酶II启动子转录的正调控、信号转导、药物反应、转录正调控以及多巴胺能突触、酪氨酸代谢和色氨酸代谢通路。分子对接结果显示，LWSZD与ESR1、SIRT1和SERPINE1有较强结合力，与唑吡坦相当。在PI大鼠模型中，LWSZD治疗可有效缓解失眠症状（P<0.01），提高雌激素及其他下丘脑-垂体-卵巢（HPO）轴相关激素水平（P<0.05），促进下丘脑组织中ESR1和SIRT1的mRNA及蛋白表达（P<0.01）。
LWSZD中的活性成分阿朴啡、山茱萸宁碱和迈灵碱可能协同调节ESR1、SIRT1和SERPINE1的表达，从而改善大鼠PI。
