淫羊藿苷元治疗骨关节炎分子机制的网络药理学和生物信息学分析  

Molecular mechanism of anhydroicaritin in the treatment of osteoarthritis:an analysis based on network pharmacology and bioinformatics

作　　者：陈锋[1] 章晓云[1,2] 陈跃平 廖建钊[1] 李嘉骏 宋世雷 赖渝 Chen Feng;Zhang Xiaoyun;Chen Yueping;Liao Jianzhao;Li Jiajun;Song Shilei;Lai Yu(Department of Orthopedics,Ruikang Hospital,Guangxi University of Chinese Medicine,Nanning 530011,Guangxi Zhuang Autonomous Region,China;Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,Jiangxi Province,China)

机构地区：[1]广西中医药大学附属瑞康医院创伤骨科,广西壮族自治区南宁市530011 [2]江西中医药大学,江西省南昌市330004

出　　处：《中国组织工程研究》2021年第23期3704-3710,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金资助项目(81760796,81960803);广西自然科学基金青年基金(2020GXNSFBA159053),项目负责人:章晓云;广西高校青年教师基础能力提升项目(2019KY0352);广西中医药大学2019年校级科研课题(2019QN027);广西中医药大学一流学科课题(2019XK026,2019XK029);广西崇左市科技计划项目(崇科FC2019006);2016年全国名老中医传承工作室建设项目(桂卫中医发{2016}11号);广西中医药大学岐黄工程高层次人才团队培育项目(04B1804804)。

摘　　要：背景:现代药理学研究表明淫羊藿苷元具有雌激素样作用,对骨关节炎的治疗起着非常积极的作用。由于淫羊藿苷元在分子水平上治疗骨关节炎的机制尚不明确,因此利用网络药理学和生物信息学从分子水平来探究淫羊藿苷元治疗骨关节炎的作用机制,可为后期药物研发及疾病治疗提供一定理论依据。目的:基于网络药理学和生物信息学初步探讨淫羊藿苷元治疗骨关节炎的关键分子机制,为骨关节炎的治疗提供新的靶点。方法:通过TCMSP数据库来评估淫羊藿苷元的药物动力学特性,检索GEO数据库中关于淫羊藿苷元和骨关节炎的相关芯片,借助R语言分析差异基因,分别构建淫羊藿苷元和骨关节炎差异基因的蛋白互作网络来明确淫羊藿苷元治疗骨关节炎的关键基因,并在淫羊藿苷元和关键基因之间进行分子对接验证,最后利用DAVID数据库对关键基因进行GO和KEGG通路富集分析。结果与结论:①淫羊藿苷元的口服生物利用度为45.41%,类药性为0.44;②检索GEO数据库获得编号为GSE85871的淫羊藿苷元芯片,利用R语言分析筛选出152个差异基因;检索GEO数据库获得编号为GSE1919的骨关节炎芯片,利用R语言分析筛选出1142个差异基因;③通过GeneMANIA数据库分别构建淫羊藿苷元和骨关节炎作用靶点的PPI网络图,利用R语言映射获得44个关键基因;④通过分子对接验证得到淫羊藿苷元和关键基因之间具有良好的结合活性;⑤通过DAVID数据库富集分析显示,淫羊藿苷元治疗骨关节炎的生物学过程主要涵盖对钙离子及金属离子、类固醇激素、有机磷的反应等,信号通路主要涉及MAPK信号通路、破骨细胞分化通路、PI3K-AKT信号通路、白细胞介素17(IL−17)信号通路等。利用网络药理学和生物信息学对GEO数据库的原始基因芯片数据进行了有效的分析,通过分析芯片内含的生物学信息,不仅能识别目前已知的�BACKGROUND:Modern pharmacological studies have shown that anhydroicaritin has an estrogen-like effect and plays a very positive role in the treatment of osteoarthritis.Because of anhydroicaritin's unclear mechanism underlying the treatment of osteoarthritis at the molecular level,network pharmacology and bioinformatics are introduced to explain the potential molecular mechanism of anhydroicaritin in the treatment of osteoarthritis.This can provide a theoretical basis for future drug development and disease treatment.OBJECTIVE:To preliminarily analyze the key molecular mechanism of anhydroicaritin in the treatment of osteoarthritis based on network pharmacology and bioinformatics,thereby providing new potential targets in treating osteoarthritis.METHODS:The pharmacokinetic properties of anhydroicaritin were assessed using TCMSP database.The GEO databases were searched for chips related to anhydroicaritin and osteoarthritis.The differentially expressed genes were analyzed by R language.Then protein-protein interaction networks of anhydroicaritin and osteoarthritis-related differential genes were respectively constructed to screen the hub genes of anhydroicaritin in the treatment of osteoarthritis,and molecular docking verification between anhydroicaritin and hub genes was performed.Finally,the DAVID database was used to enrich the hub genes for GO and KEGG pathway analysis.RESULTS AND CONCLUSION:The oral bioavailability and drug-likeness of anhydroicaritin were 45.41%and 0.44,respectively.The anhydroicaritin and osteoarthritis chips numbered GSE85871 and GSE1919 respectively were obtained in the GEO database,and the R language analysis screened out 152 and 1142 differential genes,respectively.The GeneMANIA database was used to construct the protein-protein interaction networks of the targets of anhydroicaritin and osteoarthritis,and 44 hub genes were merged by R language.We used molecular docking to find that anhydroicaritin and hub genes have good binding activity.The enrichment analysis of the DAVID database show

关 键 词：骨关节炎 骨 淫羊藿苷元 生物信息学 网络药理学 GEO数据库 分子对接 

分 类 号：R459.9[医药卫生—治疗学] R242[医药卫生—临床医学]