摘要
目的探讨中医经典方剂在类风湿关节炎(RA)治疗中的用药规律与组方特征,并利用网络药理学方法阐释其核心活性成分的作用机制。方法选取临床常用于RA治疗的5种经典方剂(麻黄加术汤、桂枝芍药知母汤、宣痹汤、独活寄生汤及补肾驱寒治尪汤)。通过TCMSP数据库筛选复方活性成分并预测潜在作用靶点,同时结合GeneCards数据库获取RA相关靶点基因,采用Venn分析获得5种方剂的共同作用靶点及药物-疾病交集靶点。利用STRING数据库构建蛋白质互作(PPI)网络,基于拓扑学参数筛选关键调控靶点,并在R 4.4.2中进行GO功能和KEGG通路富集分析,解析其作用机制。结果5种方剂共包含37味中药,去重后获得287种活性成分,对应695个潜在作用靶点。其中,β-谷甾醇、豆甾醇、山奈酚、槲皮素和儿茶素为出现频率最高的5种活性成分。5方共有199个共同靶点,RA相关靶点共4210个,药物-疾病交集靶点140个,连接度最高的5种化合物为槲皮素、木犀草素、山奈酚、汉黄芩素和β-谷甾醇。核心作用靶点包括蛋白激酶B(AKT1)、肿瘤坏死因子(TNF)、白细胞介素(IL)-6、TP53和IL-1β等。GO功能分析表明,这些靶点主要涉及外源性药物反应、分子刺激应答、激酶调节活性、细胞膜与囊泡功能等生物过程;KEGG富集分析显示,其主要作用通路包括糖化终产物及其受体(AGE-RAGE)信号通路、磷脂酰肌醇3激酶-蛋白激酶(PI3K-Akt)信号通路、动脉粥样硬化及IL-17信号通路等。结论上述5种经典方剂可能通过多成分、多靶点、多通路协同作用发挥治疗RA的作用。本研究为RA的机制研究与临床应用提供了理论参考。
Objective To investigate the medication patterns and formulation characteristics of classical traditional Chinese medicine(TCM)prescriptions for rheumatoid arthritis(RA)treatment and to elucidate the mechanisms of their core active compounds using network pharmacology.Methods Five classical TCM prescriptions commonly used in RA treatment were selected,which were Mahuang Jiazhu decoction,Guizhi Shaoyao Zhimu decoction,Xuanbi decoction,Duhuo Jisheng decoction,and Bushen Quhan Zhiwang decoction.Active compounds were screened using the TCMSP database to predict potential targets,and RA-related disease target genes were obtained from the GeneCards database.Common targets among the five prescriptions as well as drug-disease intersection targets were dentified by Venn analysis.A protein-protein interaction(PPI)network was constructed using the STRING database,and key regulatory targets were identified based on topological parameters.GO and KEGG pathway enrichment analyses were conducted in R 4.4.2 to elucidate the mechanisms of action.Results The five prescriptions contained a total of 37 Chinese herbal medicines,from which 287 active compounds were identified after deduplication,corresponding to 695 potential targets.The top five most frequently occurring active compounds wereβ-sitosterol,stigmasterol,kaempferol,quercetin,and catechin.A total of 199 common targets were obtained from the five prescriptions,and 4,210 RArelated targets were retrieved,with 140 overlapping drug-disease targets identified.The compounds with the highest degrees were quercetin,luteolin,kaempferol,wogonin,andβ-sitosterol,while the core targets included AKT1,TNF,IL6,TP53,and IL1B.GO enrichment analysis indicated that these targets are primarily involved in biological processes such as response to xenobiotic stimulus,response to molecular stimulus,kinase regulator activity,and cellular membrane and vesicle functions.KEGG enrichment analysis revealed that the main pathways involved include the AGE-RAGE signaling pathway,PI3K-Akt signaling pathway,atherosclerosis,and IL-17 signaling pathway.Conclusion The active compounds of these five classical prescriptions may exert therapeutic effects on RA through multi-target and multi-pathway synergistic mechanisms.This study provides a theoretical basis for further basic research and clinical application in RA treatment.
作者
朱珊珊
周军挺
吴婷
ZHU Shanshan;ZHOU Junting;WU Ting(Department of Pharmacy,Lishui People's Hospital,Lishui 323000,Zhejiang Province,China)
出处
《药学前沿》
2025年第8期1280-1287,共8页
China Pharmacist
关键词
类风湿关节炎
网络药理学
核心成分
GO功能分析
KEGG通路富集分析
多靶点
Rheumatoid arthritis
Network pharmacology
Core active components
GO functional analysis
KEGG pathway enrichment analysis
Multi-targets
