基于网络药理学探讨桂枝茯苓丸治疗良性前列腺增生的作用机制

Study on Mechanism of Guizhi Fuling Pill in the Treatment of Benign Prostatic Hyperplasia based on Network Pharmacology

目的:采用网络药理学方法探究桂枝茯苓丸治疗良性前列腺增生的作用机制。方法:运用中药系统药理学数据库及分析平台(TCMSP)筛选桂枝茯苓丸所含重要化学成分,利用BATMAN数据库、CTD数据库筛选成分靶蛋白,利用Metascape对靶蛋白GO BP、KEGG pathway及Reactome Gene Sets富集分析,利用cytoscape构建"成分-靶蛋白-通路"药理学网络图,并通过Autodock软件对关键小分子和靶标之间的分子对接验证。结果:通过网络药理学对桂枝茯苓丸分析得到14种关键成分,对应44个关键靶标,其中ESR1、ANXA1、PRKCA、AR、RXRA属于关键成分网络关系中的hub蛋白。关键靶标对应20条关键的相关通路,包括细胞对药物的反应、肌肉收缩的调节、一元羧酸代谢过程、生殖过程中的发育过程、维生素D代谢过程、心肌细胞中的肾上腺素能信号、细胞酮代谢过程、消化、细胞对异生素刺激的反应、有机羟基化合物代谢过程、类固醇代谢过程、对有机磷的反应、上皮细胞增殖、细胞对脂质的反应、类固醇分解代谢过程、对雌二醇的反应、女性生殖器发育类固醇激素的代谢、对维生素D的反应、内分泌和其他因素调节的钙重吸收。通过分子对接,得到白桦脂酸(Mairin)与雌激素受体α(ESR1)对接的最优模型,证明ESR1为Mairin的潜在靶标。结论:桂枝茯苓丸可能作用机制为白桦脂酸发挥雌激素样作用,与雌激素受体α结合,抑制前列腺增生。

Objective: To explore the mechanism of Guizhi fuling pill in the treatment of benign prostatic hyperplasia based on network pharmacology.Methods: TCMSP was used to screen out the main active constituents of Guizhi fuling pill.BATMAN database and CTD database were used to screen out the target proteins of the constituents, Metascape soft was used for GO BP,KEGG pathway and Reactome Gene Sets enrichment analysis of the target proteins, the "compounds-target proteins-pathways" pharmacologic network diagram was built by cytoscape, the molecular docking between the key small molecule and target was verified by Autodock software.Results: Fourteen key constituents in Guizhi fuling pill were screened out and forty-four related targets were obtained by network pharmacology, among them, ESR1,ANXA1,PRKCA,AR and RXRA were hub proteins in the network relationships of key components.The key targets corresponded to 20 key pathways, including cell response to drugs, regulation of muscle contraction, monocarboxylic acid metabolism, the developmental process of reproduction, vitamin D metabolism, adrenergic signaling in cardiac myocytes, cytoketone metabolism, digestion, cellular response to ectogenin stimulation, metabolic process of organic hydroxyl compounds, metabolic process of steroid, reaction to organophosphorus, epithelial cell proliferation, cellular response to lipids, steroid catabolism, response to estradiol, metabolism of steroid hormones for female genital development, response to vitamin D,endocrine and other factors that regulated calcium reabsorption.By means of molecular docking, the optimal model for the docking of betulinic acid(Mairin)with estrogen receptor α(ESR1)was obtained, which proved that ESR1 was a potential target of Mairin.Conclusion: Guizhi fuling pill may play an estrogen-like role in the mechanism of betulinic acid and estrogen receptor α binding, inhibit prostatic hyperplasia.