基于网络药理学研究灵芝治疗骨质疏松症的分子机制  

Exploration into Molecular Mechanism of Ganoderma in the Treatment of Osteoporosis by Network Pharmacology

作　　者：冯平 李晓峰 霍乐乐 FENG Ping;LI Xiao-feng;HUO Le-le(Luoyang Orthopedic-Traumatological Hospital Of Henan Province(Henan Provincial Orthopedic Hospital),Zhengzhou 450016,China)

机构地区：[1]河南省洛阳正骨医院(河南省骨科医院),郑州450016

出　　处：《中国合理用药探索》2023年第10期116-122,共7页Chinese Journal of Rational Drug Use

基　　金：河南省中医药科学研究专项课题(2015ZY02068)。

摘　　要：目的:应用网络药理学方法对灵芝治疗骨质疏松症的主要活性成份及可能作用机制进行预测分析。方法:分别在中药系统药理学数据库与分析平台(TCMSP)、OMIM等数据库检索并筛选灵芝的活性成份及骨质疏松症相关靶点;利用Cytoscape3.2.1软件构建“灵芝活性成份-骨质疏松症-共同靶点”网络,采用String数据库构建蛋白质相互作用网络筛选关键靶点,利用David数据库对共同靶基因进行基因本体(GO)分析和京都基因与基因组百科全书(KEGG)分析。结果:筛选得到灵芝与骨质疏松症相关的61种活性成份和21个共同靶基因。其中β-谷甾醇、环氧灵芝醇B、环氧灵芝醇C、麦角甾-4,7,22-三烯-3,6-二酮、灵芝酮三醇、灵芝醇A、Lucialdehyde A、LucialdehydeB是灵芝治疗骨质疏松症的主要活性成份;MAPK3、MAPK1、NR3C1、ESR1、AR、CYP19A1、NOS3、HIF1A是骨质疏松症的治疗中的核心靶点。GO分析和KEGG分析显示,灵芝治疗骨质疏松症主要涉及核受体的活性、配体激活的转录因子活性、类固醇结合、类固醇激素受体活性、DNA结合转录激活剂活性、RNA特异性聚合酶Ⅱ等生物学过程,通过参与调节催乳素信号通路、雌激素信号通路、肾细胞癌、乳腺癌等发挥抗骨质疏松作用。结论:通过网络药理学初步预测了灵芝治疗骨质疏松症的潜在活性成份及其可能机制,揭示其可通过多成份、多靶点、多途径的方式发挥作用,为进一步开展灵芝抗骨质疏松作用机制的研究提供了新思路和新方法。Objective:The biological processes were employed to analyze the active ingredients and the potential molecular mechanism of Ganoderma in the treatment of osteoporosis(OP).Methods:The main active ingredients of Ganoderma and OP related targets were screened in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database and OMIM database.The ganoderma-active ingredients-potential targets network was constructed using Cytoscape3.2.1 software.The protein-protein interactions network mapping was constructed using the String database to select the key targets.The gene oncology(GO) and KEGG of the key targets were analyzed using DAVID.Results:A total of 61 active ingredients and 21 common targets of Ganoderma for OP treatment were screened.Among the active ingredients,beta-sitosterol,epoxyganoderiol B,epoxyganoderiol C,ergosta-4,7,22-trien-3,6-dione,ganodermatriol,ganodermenonol,Lucialdehyde A,Lucialdehyde B are the main active ingredients of Ganoderma in treating OP.MAPK3,MAPK1,NR3C1,ESR1,AR,CYP19A1,NOS3 and HIF1A are the key targets in treating OP.The GO-biological process and KEGG pathways enrichment analysis showed that the mechanisms of Ganoderm in treating OP mainly involve nuclear receptor activity,ligand-activated transcription factor activity,steroid binding,steroid hormone receptor activity,DNA-binding transcription activator activity,RNA polymerase Ⅱ-specific,by regulating prolactin signaling pathway,estrogen signaling pathway,renal cell carcinoma,breast cancer,and other signaling pathways to exert its anti-osteoporosis effect.Conclusion:The potential active ingredients of Ganoderma in the treatment of OP and their possible mechanisms were preliminarily predicted through network pharmacological,which revealed that it could play its role through multi-ingredients,multi-targets and multi-channels,providing new ideas and methods for further research on the anti-osteoporosis mechanism of Ganoderma.

关 键 词：灵芝 骨质疏松 网络药理学 生物过程 信号通路 

分 类 号：R285[医药卫生—中药学]