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

Abstract

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.

Sigesbeckia orientalis L. Extract Alleviated the Collagen Type II–Induced Arthritis Through Inhibiting Multi-Target–Mediated Synovial Hyperplasia and Inflammation

“…According to our previous results from computational predictions, RA was frequently involved in multiple signal pathways ( Wang et al, 2019 ). The interactions of these pathways were associated with pathological mechanisms of RA.…”

Chinese Herbal Formula Huayu-Qiangshen-Tongbi Decoction Compared With Leflunomide in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis: An Open-Label, Randomized, Controlled, Pilot Study

“…Previous studies have shown that herbal medicine monotherapy or combination therapy has efficacy in relieving clinical symptoms, signs, and indicators of inflammatory activity for RA patients ( 12 , 32 ). According to previous pharmacological studies, the herbals in HQT formula are proven to have a variety of pharmacological effects, such as anti-inflammatory properties, analgesia, and immune suppression ( 33 , 34 ), supporting the clinical efficacy of HQT in RA treatment. The root and rhizoma of S. miltiorrhiza Bunge (Danshen) and the rhizoma of D. nipponica Makino (Chuanshanlong) are the most important components of HQT.…”

“…Previous studies have shown that herbal medicine monotherapy or combination therapy has efficacy in relieving clinical symptoms, signs, and indicators of inflammatory activity for RA patients (12,32). According to previous pharmacological studies, the herbals in HQT formula are proven to have a variety of pharmacological effects, such as anti-inflammatory properties, analgesia, and immune suppression (33,34) fibroblast-like synoviocytes obtained from RA patients (35,36). Also, tanshinone VI, an abietane diterpene extracted from the root of S. miltiorrhiza Bunge, could improve bone loss by inhibiting osteoclastic bone resorption through inhibition of nuclear factor-κB and receptor activator of nuclear factor kappaκ ligand pathways (37).…”

Traditional Chinese medicine Biqi capsule compared with leflunomide in combination with methotrexate in patients with rheumatoid arthritis: a randomized controlled trial

“…Previously, we have explored potential mechanisms of action (MoA) for TCMs in treating RA and other rheumatic disorders through a number of pre-clinical studies including in silico network modeling [20], in vitro cellular assays [20,21] and in vivo animal experiment [22]. Although insightful, results of these studies warrant further validation in the clinical settings.…”