Periplogenin inhibits pathologic synovial proliferation and infiltration in rheumatoid arthritis by regulating the JAK2/3-STAT3 pathway

• Published in: International immunopharmacology 2024-02, Vol.128, p.111487-111487, Article 111487
• Main Authors: Zhong, Xiaoqin, Feng, Wei, Liu, Lianjie, Liu, Qingping, Xu, Qiang, Liu, Minying, Liu, Xiaobao, Xu, Shudi, Deng, Minzhen, Lin, Changsong
• Format: Article
• Language: English
• Subjects: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Cell Proliferation; Cells, Cultured; Digitoxigenin - analogs & derivatives; Fibroblasts; Humans; Inflammation - metabolism; JAK2/3-STAT3; Janus Kinase 2 - metabolism; Periplogenin; Rheumatoid arthritis; STAT3 Transcription Factor - metabolism; Synovial fibroblasts; Synovial Membrane - pathology; Synoviocytes
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2024.111487

•The migration and infiltration of fibroblast-like synoviocytes in rheumatoid arthritis have been observed both in vivo and in vitro studies.•The JAK2/3-STAT3 pathway was activated in both in vivo and in vitro studies.•Periplogenin has been found to inhibit the activation of the JAK2/3-STAT3 pathway in both in vivo and in vitro studies, which can help alleviate the symptoms of rheumatoid arthritis. Rheumatoid arthritis (RA) is an autoimmune disease that affects joints, causing inflammation, synovitis, and erosion of cartilage and bone. Periplogenin is an active ingredient in the anti-rheumatic and anti-inflammatory herb, cortex periplocae. We conducted a study using a CIA model and an in vitro model of fibroblast-like synoviocytes (FLS) induced by Tumor Necrosis Factor-alpha (TNF-α) stimulation. We evaluated cell activity, proliferation, and migration using the CCK8 test, EDU kit, and transwell assays, as well as network pharmacokinetic analysis of periplogenin targets and RA-related effects. Furthermore, we measured inflammatory factors and matrix metalloproteinases (MMPs) expression using ELISA and qRT-PCR assays. We also evaluated joint destruction using HE and Safranin O-Fast Green Staining and examined the changes in the JAK2/3-STAT3 pathway using western blot. The results indicated that periplogenin can effectively inhibit the secretion of inflammatory factors, suppress the JAK2/3-STAT3 pathway, and impede the proliferation and migration of RA FLS. Thus, periplogenin alleviated the Synovial inflammatory infiltration of RA.