桃红四物汤“异病同治”类风湿性关节炎和骨关节炎的网络药理学及分子对接分析

Network pharmacology and molecular docking analysis on Taohong Siwu Decoction for rheumatoid arthritis and osteoarthritis based on the concept of“Treating Different Diseases with the Same Therapeutic Principle”

背景:桃红四物汤已成为中医临床使用最广泛的活血化瘀方剂之一,也是异病同治的典型方剂。但是中药复方化学成分复杂,临床疗效的表现是其多成分、多靶点、多途径的协同作用;网络药理学的整体性、系统性和注重药物间相互作用的特点与中医药学的基本特点相吻合。运用网络药理学与生物信息学阐述经典名方与疾病可能潜在的成分-靶点-通路-疾病之间的关联,是该方剂现代应用中亟待探究的关键问题。目的:运用网络药理学、生物信息学和分子对接方法,基于异病同治的思想,探讨桃红四物汤治疗类风湿性关节炎和骨关节炎的分子机制。方法:利用GEO数据库筛选与类风湿性关节炎和骨关节炎作用的靶点,运用Cytoscape对化合物-靶点网络可视化,DAVID数据库进行GO、KEGG富集分析,并对核心靶点进行分子对接。结果与结论:筛选出有效化合物44个;与类风湿性关节炎和骨关节炎相关的靶点201个;GO、KEGG分析主要与AGE-RAGE,MAPK,IL-17等信号通路相关;通过分子对接验证实验可知,桃红四物汤可能主要通过常春藤素、芍药苷、β-胡萝卜素、豆甾醇等有效化合物发挥治疗类风湿性关节炎和骨关节炎的作用。说明桃红四物汤治疗类风湿性关节炎和骨关节炎是通过IL-17信号通路、AGEs/AGE-RAGE信号通路、TNF信号通路、MAPK信号通路、Toll样受体信号通路等信号通路,促使促凋亡和抗凋亡信号之间的平衡,减少炎症细胞因子的分泌,从而延缓或改善骨关节软骨的退变,为桃红四物汤治疗类风湿性关节炎和骨关节炎作用机制的方法研究提供了新思路和新方法。

BACKGROUND:Taohong Siwu Decoction has become one of the most widely used clinical prescriptions for promoting blood circulation and removing blood stasis in Chinese medicine,and it is also a typical prescription for treating different diseases with the same treatment.However,the chemical components of traditional Chinese medicine compounds are complex,and the clinical efficacy is manifested by the synergy of its multiple components,multiple targets,and multiple pathways.The integrality,systemicity,and emphasis on drug interactions of network pharmacology are similar to the basic characteristics of traditional Chinese medicine.The use of network pharmacology and bioinformatics to explain the relationship between the classic prescription and the possible potential component-target-pathway-disease of the disease is a key issue that needs to be explored in the modern application of the prescription.OBJECTIVE:To explore the molecular mechanism of Taohong Siwu Decoction in the treatment of rheumatoid arthritis and osteoarthritis based on the idea of“Treating Different Diseases with the Same Therapeutic Principle”by using network pharmacology,bioinformatics,and molecular docking methods.METHODS:The GEO database was used to screen the targets that interact with rheumatoid arthritis and osteoarthritis.Cytoscape was used to visualize the compound-target network.The DAVID database was used for GO and KEGG enrichment analysis,and the core targets were molecularly docked.RESULTS AND CONCLUSION:Totally 44 effective compounds were screened;201 targets related to rheumatoid arthritis and osteoarthritis.GO and KEGG analyses were mainly related to AGE-RAGE,MAPK,and IL-17 signaling pathways.The molecular docking verification experiment demonstrated that Taohong Siwu Decoction is mainly used to treat rheumatoid arthritis and osteoarthritis through effective compounds,such as hederin,paeoniflorin,β-carotene,and stigmasterol.It is concluded that Taohong Siwu Decoction treats rheumatoid arthritis and osteoarthritis through IL-17 signaling pathway,AGEs/AGE-RAGE signaling pathway,TNF signaling pathway,MAPK signaling pathway,and Toll-like receptor signaling pathway to promote the balance between pro-apoptotic and anti-apoptotic signals,reduces the secretion of inflammatory cytokines,thereby delaying or improving the degeneration of bone and articular cartilage,which provides new ideas and new methods for the study regarding the mechanism of action of Taohong Siwu Decoction in the treatment of rheumatoid arthritis and osteoarthritis.