基于网络药理学探讨山茱萸治疗骨质疏松症的作用机制

Discussion on the mechanism of action of cornus in the treatment of osteoporosis based on network pharmacology

目的:基于网络药理学方法分析山茱萸治疗骨质疏松症(Osteoporosis,OP)的药理机制。方法:通过中医药系统药理学平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)数据库及相关文献获取山茱萸的主要化合物信息及相关靶点,根据ADME筛选中药活性组分;通过Gen Cards、TTD、DRUGBANK数据库获取OP的主要靶点,将中药靶点与疾病靶点取交集,利用String数据库进行蛋白质相互作用分析,构建高度置信PPI网络并挖掘网络中潜在的蛋白质功能模块。采用David平台进行GO生物功能富集分析与KEGG通路富集分析,得出山茱萸-骨质疏松症靶点的相关通路。结果:山茱萸调治OP的核心活性成分为β-谷甾醇、山茱萸新苷、四氢鸭脚木碱、去氮腺嘌呤等,核心靶点有转录后基因沉默(PostTranscriptional Gene Silencing,PTGS)、PTGS2、雄激素受体(Androgen Receptor, AR)、肿瘤坏死因子(Tumor Necrosis Factor,TNF)、白蛋白(Albumin,ALB)等。山茱萸调治OP的生物学通路主要作用于癌症通路、TNF信号通路、非酒精性肝病通路等信号通路,其功能主要为破骨细胞分化的调控、核因子-κb(Nuclear Factor-κB,NF-κB)导入细胞核的调控、基因表达的正调控、骨矿化、核糖核酸(Ribonucleic Acid,RNA)聚合酶II启动子的转录起始、类固醇激素介导的信号通路、细胞增殖等。结论:本研究初步揭示了山茱萸调治OP的多成分、多靶点、多通路的作用机制,为山茱萸的临床开发利用提供基础。

Objective: To analyze the pharmacological mechanism of cornus in the treatment of osteoporosis based on network pharmacology. Methods: Through the TCMSP database and related literature, the main compound information and related targets of cornus officinalis were obtained, and the active components of TCM medicine were screened according to ADME. The main target is to take the intersection of the Chinese medicine target and the disease target, use the String database to analyze the protein interaction, build a highlyconfidence PPI network and explore the potential protein functional modules in the network. The David platform was used to carry out the GO biological function enrichment analysis and the KEGG pathway enrichment analysis, and the relevant pathways of the dogwoodosteoporosis target were obtained. Results: The core active ingredients of cornus for treating osteoporosis were β-sitosterol, cornus neoglycoside, tetrahydroattorine, deazaadenine, etc.. The core targets were PTGS1, PTGS2, AR, TNF, ALB, etc.. The biological pathways of cornus for treating osteoporosis mainly act on the cancer pathway, TNF signaling pathway, non-alcoholic liver disease pathway and other signaling pathways. Its functions are mainly the regulation of osteoclast differentiation, the regulation of NF-κB into the nucleus,and gene expression. The positive regulation of bone mineralization, RNA polymerase II promoter transcription initiation, steroid hormonemediated signaling pathway, cell proliferation, etc.. Conclusion: This study has initially revealed the multi-component, multi-target, and multi-path mechanism of cornus for the treatment of osteoporosis, which provides a basis for the clinical development and utilization of cornus.