菟丝子治疗骨关节炎:网络药理学分析及实验验证  

Semen cuscutae in the treatment of osteoarthritis:network pharmacology analysis and experimental validation

作　　者：张天栋 彭青平 刘欢 冯建国 易茜 黄文华 Zhang Tiandong;Peng Qingping;Liu Huan;Feng Jianguo;Yi Qian;Huang Wenhua(School of Integrated Traditional Chinese and Western Medicine,Southwest Medical University,Luzhou 646000,Sichuan Province,China;Department of Orthopedics,The Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University,Luzhou 646000,Sichuan Province,China;Department of Anesthesiology,the Affiliated Hospital of Southwest Medical University,Luzhou 646000,Sichuan Province,China;Department of Physiology,School of Basic Medical Science,Southwest Medical University,Luzhou 646000,Sichuan Province,China;Guangdong Engineering Research Center for Translation of Medical 3D Printing Application,Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics,National Key Discipline of Human Anatomy,Southern Medical University,Guangzhou 510515,Guangdong Province,China)

机构地区：[1]西南医科大学,中西医结合学院,四川省泸州市646000 [2]西南医科大学,西南医科大学附属中医医院骨科,四川省泸州市646000 [3]西南医科大学附属医院麻醉科,四川省泸州市646000 [4]西南医科大学,基础医学院生理学院,四川省泸州市646000 [5]南方医科大学基础医学院人体解剖学国家重点学科,广东省数字医学与生物力学重点实验室,广东省医学3D打印应用转化工程技术研究中心,广东省广州市510515

出　　处：《中国组织工程研究》2024年第28期4516-4521,共6页Chinese Journal of Tissue Engineering Research

基　　金：西南医科大学高层次人才(钟世镇团队)专项支援项目(02061648361),项目负责人:黄文华;国家重点研发计划项目(2022YFB4600600),项目负责人:黄文华;国家自然科学基金项目(32271181),项目负责人:黄文华;泸州市科技计划项目(2021-JYJ-71),项目负责人:易茜;四川省科技计划联合创新专项项目(2022YFS0609),项目负责人:易茜;四川省自然科学基金项目(22NSFSC3871),项目负责人:易茜。

摘　　要：背景:菟丝子具有补肝肾、益精髓的功效,而骨关节炎的主要病机为肝肾亏虚,推测菟丝子与骨关节炎之间有一定的联系。目的:基于网络药理学和分子对接的分析手段挖掘骨关节炎和菟丝子之间的潜在联系,对中药本草菟丝子的作用机制进行合理的推测与验证。方法:先在中草药数据库TCMSP中筛选菟丝子的有效活性成分和作用靶点,另在疾病数据库GeneCards、OMIM、TTD中收集骨关节炎的相关基因;取交集后进行一系列分析,并筛选出核心基因;通过对核心基因的富集分析选择菟丝子作用于骨关节炎的通路,通过分子对接验证核心基因的作用,并依此选择合适的有效活性成分进行实验验证。结果与结论:①筛选出11种菟丝子的有效活性成分,菟丝子和骨关节炎有66个交集靶点基因,后续筛选出12个核心基因,包括肿瘤坏死因子、白细胞介素1B、TP53、RACα丝氨酸/苏氨酸蛋白激酶(AKT1)、血管内皮生长因子A、基质金属蛋白酶9、前列腺素过氧合酶2、胱天蛋白酶3、表皮生长因子、过氧化物酶体增生激活受体γ、白细胞介素10、血管细胞黏附因子1;②对核心基因进行富集分析后,选择经典炎症通路核因子κB信号通路进行后续菟丝子缓解骨关节炎炎症的分析验证;根据各活性成分和通路核心基因前列腺素过氧合酶2进行分子对接后得到的结果,选择亲和力最高的芝麻素进行后续细胞实验验证,结果证实了菟丝子的有效成分芝麻素可以通过抑制白细胞介素1β诱导的核因子κB信号通路降低环氧合酶2的表达;③结果表明,菟丝子的活性有效成分芝麻素通过抑制白细胞介素1β诱导的核因子κB信号通路降低环氧合酶2的表达,达到改善骨关节炎炎症的作用,证实了菟丝子在骨关节炎方面的治疗效果。BACKGROUND:Semen cuscutae has the effect of tonifying the liver and kidney system and benefiting the essence.The main pathogenesis of osteoarthritis is deficiency of the liver and kidneys.Therefore,it is hypothesized that there is a link between semen cuscutae and osteoarthritis.OBJECTIVE:To explore the potential relationship between osteoarthritis and semen cuscutae and validate the mechanism of semen cuscutae based on the network pharmacology and molecular docking analysis.METHODS:First,the active ingredients and targets of semen cuscutae were screened in TCMSP,and the genes related to osteoarthritis were collected in the disease databases GeneCard’s,OMIM and TTD.The intersected genes were taken and then subjected to a series of analyses and screened for hub genes.Through the enrichment analysis of hub genes,the pathway of semen cuscutae acting on osteoarthritis was selected.The role of hub genes was verified by molecular docking.Therefore,the appropriate active ingredients of semen cuscutae were selected for experimental verification.RESULTS AND CONCLUSION:There were 11 active ingredients of semen cuscutae,66 intersection target genes of semen cuscutae and osteoarthritis,and 12 hub genes,including tumor necrosis factor,interleukin 1B,TP53,RAC-alpha serine/threonine protein kinase(AKT1),vascular endothelial growth factor A,matrix metalloproteinase 9,prostaglandin peroxidase 2,cystatinase 3,epidermal growth factor,peroxisome proliferator-activated receptor gamma,interleukin 10,vascular cell adhesion factor 1.After the enrichment analysis of the hub genes,the classical inflammatory pathway,nuclear factor-κB signaling pathway,was selected for subsequent validation of semen cuscutae to alleviate osteoarthritic inflammation.Through the results obtained after molecular docking of each active ingredient and the hub gene of the pathway prostaglandin peroxidase 2,sesamin with the highest affinity was selected for subsequent cell experiments,and the experimental results confirmed that sesamin,the active ingredient of

关 键 词：菟丝子 骨关节炎 芝麻素 核因子ΚB信号通路 环氧合酶2 网络药理学 分子对接 炎症反应 

分 类 号：R459.9[医药卫生—治疗学] R319[医药卫生—临床医学] R684.3