Inhibitory Effect of Jinwujiangu Prescription on Peripheral Blood Osteoclasts in Patients with Rheumatoid Arthritis and the Relevant Molecular Mechanism

• Published in: Mediators of inflammation Vol. 2023; pp. 4814412 - 17
• Main Authors: Huang, Ying, Gao, Xueqin, An, Yang, Zeng, Ping, Chen, Changming, Ma, Wukai, Yao, Xueming
• Format: Journal Article
• Language: English
• Published: United States Hindawi 08.02.2023; John Wiley & Sons, Inc; Hindawi Limited
• Subjects: Apoptosis; Arthritis; Arthritis, Rheumatoid - metabolism; Autoimmune diseases; Autophagy; Care and treatment; Cell culture; Cholecystokinin; Disease; Drug dosages; Flow cytometry; Humans; Hydroxychloroquine; Hypoxia-inducible factor 1a; Interleukin 17; Leukocytes, Mononuclear - metabolism; Medicine, Chinese; Medicine, Chinese Traditional; Molecular modelling; NF-κB protein; Osteoclasts; Osteoclasts - metabolism; Pathogenesis; Peripheral blood mononuclear cells; Pharmacology; Rheumatoid arthritis; Rheumatoid factor; Signal transduction; Toll-like receptors; TOR protein; TOR Serine-Threonine Kinases - metabolism; Toxicity; Traditional Chinese medicine; China
• ISSN: 0962-9351; 1466-1861
• DOI: 10.1155/2023/4814412

Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease characterized with high recurrence, high disability, poor prognosis, and long treatment cycles. Versus western medicine, traditional Chinese medicine has the traits of definite efficacy, low toxicity, and side effects in the treatment of RA. Moreover, traditional Chinese medicine also has the advantages of multiple targets, multiple links, and multiple approaches. This study was committed to exploring the effect of Jinwujiangu prescription on peripheral blood osteoclasts in those patients with RA and relevant molecular mechanisms. We first identified 159 common targets by online pharmacology, and there were correlations among these targets; besides, the main signaling pathways involved were inclusive TNF signaling pathway, rheumatoid arthritis, IL-17 signaling pathway, NF-kappa B signaling pathway, Toll-like receptor signaling pathway, etc. Through experimental verification, we found that PBMC cells extracted from human peripheral blood could be successfully induced into osteoclasts, and Jinwujiangu prescription inhibited the generation of osteoclasts from PBMCs of RA patients. CCK-8 and flow cytometry showed that osteoclast viability was significantly decreased and osteoclast apoptosis was significantly increased in the HIF-1α interference group; low-, medium-, and high-dose Jinwujiangu prescription groups; sinapine group; and hydroxychloroquine control group. Moreover, Jinwujiangu prescription and sinapine could inhibit the production of cytokines in peripheral blood osteoclasts and inhibit autophagy in RA patients. The expression level of mTOR was significantly increased in both Jinwu middle- and high-dose groups. In conclusion, this study demonstrated that sinapine, the active target in Jinwujiangu prescription, can act as a HIF-1α inhibitor; activate the mTOR pathway; downregulate the level of autophagy rate, ATG5, beclin-1, and LC3 expression; and inhibit the occurrence of autophagy. The trial registration number of the study is KYW2021010.