Gao M, Hong Y, Cui M, Huang J, Tan Y, Nie X
Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2022 Jan 20;42(1):1-12. doi: 10.12122/j.issn.1673-4254.2022.01.01.
To explore the pharmacological mechanism of (BSHT) recipe in the treatment of polycystic ovary syndrome (PCOS).
The active ingredients in the component drugs of the recipe were screened through TCMSP, and their potential targets were predicted by PubChem and Swiss target prediction. Genecards and OMIM were used to screen the therapeutic targets in the treatment of PCOS. The drug targets and disease targets were corrected using Uniprot, and the intersection targets were obtained. The protein-protein interaction (PPI) network was constructed using STRING, and the intersection targets were analyzed with CytoNCA to screen the core targets. DAVID was used for GO enrichment analysis and KEGG pathway enrichment analysis, and the core components and core targets were verified using AutoDock. Animal experiment was performed to verify the results using a female C57BL/6J mouse model of PCOS, treated daily with 1 mg/kg BSHT recipe granule for 35 days, and the ovarian expressions of the core targets and pathways were detected using Western blotting.
We identified a total of 125 potential active ingredients from the 14 component drugs in the recipe, 990 drug targets, 4759 PCOS targets and 434 intersection targets. The core active ingredients of the recipe included β -Sitosterol, kaempferol, and quercetin, whose core targets included PIK3CA, PIK3R1, APP, AKT1, and MAPK1. GO enrichment analysis highlighted such processes as drug reaction, negative regulation of apoptosis, and positive regulation of transcription from RNA polymerase Ⅱ promoter. The enriched KEGG pathways included primarily the cancer pathway and PI3K-Akt signaling pathway. Molecular docking showed that the core active ingredients had strong binding ability with the core targets. In the animal experiment, BSHT recipe was shown to improve the symptoms, down-regulate the expressions of PI3K and Akt proteins and up-regulate MAPK1 expression in the ovary of mice with PCOS.
The therapeutic mechanism of BSHT recipe for PCOS involves multiple active ingredients, multiple therapeutic targets and multiple pathways.
探讨补肾化痰活血方（BSHT）治疗多囊卵巢综合征（PCOS）的药理机制。
通过中药系统药理学数据库与分析平台（TCMSP）筛选该方组成药物中的活性成分，利用PubChem和瑞士靶点预测工具预测其潜在靶点。采用基因卡片（Genecards）和在线孟德尔人类遗传数据库（OMIM）筛选PCOS的治疗靶点。运用通用蛋白质数据库（Uniprot）对药物靶点和疾病靶点进行校正，得到交集靶点。使用STRING构建蛋白质-蛋白质相互作用（PPI）网络，并用CytoNCA分析交集靶点以筛选核心靶点。利用DAVID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）通路富集分析，并用自动对接（AutoDock）验证核心成分和核心靶点。采用动物实验进行结果验证，以雌性C57BL/6J小鼠PCOS模型为研究对象，每日给予1 mg/kg BSHT配方颗粒，连续给药35天，采用蛋白质免疫印迹法检测卵巢中核心靶点及通路的表达。
从该方14味组成药物中总共鉴定出125种潜在活性成分、990个药物靶点、4759个PCOS靶点和434个交集靶点。该方的核心活性成分包括β-谷甾醇、山柰酚和槲皮素，其核心靶点包括磷脂酰肌醇-3激酶催化亚基α（PIK3CA）、磷脂酰肌醇-3激酶调节亚基1（PIK3R1）、淀粉样前体蛋白（APP）、蛋白激酶B1（AKT1）和丝裂原活化蛋白激酶1（MAPK1）。GO富集分析突出了药物反应、凋亡负调控以及RNA聚合酶Ⅱ启动子转录正调控等过程。富集的KEGG通路主要包括癌症通路和磷脂酰肌醇-3激酶-蛋白激酶B（PI3K-Akt）信号通路。分子对接显示核心活性成分与核心靶点具有较强的结合能力。在动物实验中，BSHT配方可改善PCOS小鼠的症状，下调PI3K和Akt蛋白的表达，并上调MAPK1在卵巢中的表达。
BSHT配方治疗PCOS的作用机制涉及多种活性成分、多个治疗靶点和多条通路。
