基于网络药理学和分子对接探索红花五味子治疗多囊卵巢综合征的机制
Exploring the mechanism of Schisandra rubriflora in the treatment of polycystic ovary syndrome based on network pharmacology and molecular docking.
作者信息
Dou Zhengyan, Li Qingxian, Zhang Jing, Zhang Xin
机构信息
Department of Operation Room, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China.
Department of Reproductive Medicine Center, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China.
出版信息
J Ovarian Res. 2025 Jan 28;18(1):16. doi: 10.1186/s13048-025-01600-x.
BACKGROUND
Polycystic ovary syndrome (PCOS) is an endocrine disease associated with reproductive and metabolic abnormalities. The aim of this study was to elucidate the effects of Schisandra rubriflora (S. rubriflora) on PCOS and its related mechanisms using network pharmacology, molecular docking and in vitro experiments.
MATERIALS AND METHODS
HERB database and SwissTargetPrediction database were used to obtain the active components and the targets of S. rubriflora. Differentially expressed genes (DEGs) associated with PCOS were obtained by analyzing GSE54248 dataset. A protein-protein interaction network was constructed, and topological analyses were performed to identify the hub targets and main bioactive components. The binding abilities between hub targets and key components were studied by molecular docking. Finally, in vitro PCOS models were constructed with KGN cells and rat ovarian granulosa cells, respectively, and the regulatory effects of schisandrin, a key bioactive component of S. rubriflora, on the cells were investigated by in vitro assays.
RESULTS
A total of 14 bioactive ingredients of S. rubriflora and 26 potential therapeutic targets of S. rubriflora in PCOS treatment were obtained. Bioinformatics analyses suggested that the mechanisms of S. rubriflora in treating PCOS were related to IL-17 signaling pathway and TNF signaling pathway. The binding affinities between key components of S. rubriflora (schisandrin, wyerone, and rugosal) and hub targets (PTGS2, MMP9, MCL1, and JUN) were high. Schisandrin could attenuate lipopolysaccharide-induced inflammation, oxidative stress, and apoptosis of KGN cells and rat ovarian granulosa cells, as well as inhibit hub target expression and TNF pathway activation.
CONCLUSION
PTGS2, MMP9, MCL1 and JUN are potential targets for S. rubriflora to treat PCOS. Schisandrin, a main component of S. rubriflora, may be a candidate for the treatment of PCOS.
背景
多囊卵巢综合征（PCOS）是一种与生殖和代谢异常相关的内分泌疾病。本研究旨在利用网络药理学、分子对接和体外实验阐明红五味子（S. rubriflora）对PCOS的影响及其相关机制。
材料与方法
利用HERB数据库和SwissTargetPrediction数据库获取红五味子的活性成分和靶点。通过分析GSE54248数据集获得与PCOS相关的差异表达基因（DEGs）。构建蛋白质-蛋白质相互作用网络，并进行拓扑分析以识别核心靶点和主要生物活性成分。通过分子对接研究核心靶点与关键成分之间的结合能力。最后，分别用KGN细胞和大鼠卵巢颗粒细胞构建体外PCOS模型，并通过体外实验研究红五味子的关键生物活性成分五味子醇对细胞的调节作用。
结果
共获得红五味子的14种生物活性成分和26个在PCOS治疗中的潜在治疗靶点。生物信息学分析表明，红五味子治疗PCOS的机制与IL-17信号通路和TNF信号通路有关。红五味子的关键成分（五味子醇、异黄酮和皱波角叉菜）与核心靶点（PTGS2、MMP9、MCL1和JUN）之间的结合亲和力较高。五味子醇可减轻脂多糖诱导的KGN细胞和大鼠卵巢颗粒细胞的炎症、氧化应激和凋亡，以及抑制核心靶点表达和TNF通路激活。
结论
PTGS2、MMP9、MCL1和JUN是红五味子治疗PCOS的潜在靶点。五味子醇作为红五味子的主要成分，可能是治疗PCOS的候选药物。
Zotero 插件