Table_2_Deciphering the Pharmacological Mechanisms of the Huayu-Qiangshen-Tongbi Formula Through Integrating Network Pharmacology and In Vitro Pharmacological Investigation.xlsx

Rheumatoid arthritis is a chronic inflammatory autoimmune disease, causing articular and extra-articular dysfunctions among patients, and it could result in irreversible joint damages or disability if untreated. A traditional Chinese medicine formula, Huayu-Qiangshen-Tongbi (HT) formula, has been observed successful in controlling rheumatoid arthritis progression in traditional Chinese medicine clinics. In this study, we conducted a systematic analysis of the HT formula with a purpose of proposing for its potential mechanism of action using network pharmacological methods. The potential targets of the formula were collected and screened according to the topological features of their protein–protein interaction network, and we subsequently validated our prediction results through in vitro experiments. We proposed that the HT formula could interfere with the bone metabolism and the inflammatory pathways of the body. The experimental validation results indicated that HT formula could exhibit anti-inflammatory effects by regulating several signaling pathways specifically the Toll-like receptor signaling pathway, phosphoinositide-3-kinase–Akt signaling pathway, hypoxia-inducible factor 1 signaling pathway, mitogen-activated protein kinase signaling pathway and activator protein 1 signaling pathway.

类风湿关节炎（Rheumatoid arthritis）是一种慢性炎症性自身免疫疾病，可导致患者出现关节及关节外功能障碍，若未接受治疗，可引发不可逆的关节损伤甚至残疾。化瘀强肾通痹方（Huayu-Qiangshen-Tongbi, HT）作为一种中药方剂，在中医临床中被证实可有效控制类风湿关节炎的病情进展。本研究采用网络药理学方法对HT方剂展开系统分析，旨在阐明其潜在的作用机制。研究首先通过蛋白质相互作用网络的拓扑特征，筛选并获取该方剂的潜在作用靶点，随后通过体外实验对预测结果进行验证。本研究提出，HT方剂可干预机体的骨代谢与炎症通路；实验验证结果显示，HT方剂可通过调控多条信号通路发挥抗炎作用，具体包括Toll样受体信号通路、磷脂酰肌醇3-激酶-Akt信号通路、缺氧诱导因子1信号通路、丝裂原活化蛋白激酶信号通路以及激活蛋白1信号通路。