Berberine inhibits RA-FLS cell proliferation and adhesion by regulating RAS/MAPK/FOXO/HIF-1 signal pathway in the treatment of rheumatoid arthritis

• Published in: Bone & joint research Vol. 12; no. 2; pp. 91 - 102
• Main Authors: Li, Zhiqi, Chen, Meilin, Wang, Zhaoyi, Fan, Qiqi, Lin, Zili, Tao, Xiaoyu, Wu, Jiarui, Liu, Zhenquan, Lin, Ruichao, Zhao, Chongjun
• Format: Journal Article
• Language: English
• Published: England The British Editorial Society of Bone & Joint Surgery 01.02.2023
• Subjects: Arthritis; berberine; enzyme-linked immunosorbent assay; fibroblast-like synoviocytes; hypoxia; matrix metalloproteinases (mmps); mmp-3; polymerase chain reaction; quantitative polymerase chain reaction; rheumatoid arthritis; traditional chinese medicine; western blot; Western blot; matrix metalloproteinases (MMPs); Berberine; hypoxia; arthritis; Rheumatoid arthritis; MMP-3; Traditional Chinese medicine; quantitative polymerase chain reaction; fibroblast-like synoviocytes; Enzyme-linked immunosorbent assay; polymerase chain reaction
• ISSN: 2046-3758; 2046-3758
• DOI: 10.1302/2046-3758.122.BJR-2022-0269.R1

Rheumatoid arthritis (RA) is a common chronic immune disease. Berberine, as its main active ingredient, was also contained in a variety of medicinal plants such as Berberaceae, Buttercup, and Rutaceae, which are widely used in digestive system diseases in traditional Chinese medicine with anti-inflammatory and antibacterial effects. The aims of this article were to explore the therapeutic effect and mechanism of berberine on rheumatoid arthritis. Cell Counting Kit-8 was used to evaluate the effect of berberine on the proliferation of RA fibroblast-like synoviocyte (RA-FLS) cells. The effect of berberine on matrix metalloproteinase (MMP)-1, MMP-3, receptor activator of nuclear factor kappa-Β ligand (RANKL), tumour necrosis factor alpha (TNF-α), and other factors was determined by enzyme-linked immunoassay (ELISA) kit. Transcriptome technology was used to screen related pathways and the potential targets after berberine treatment, which were verified by reverse transcription-polymerase chain reaction (RT-qPCR) and Western blot (WB) technology. Berberine inhibited proliferation and adhesion of RA-FLS cells, and significantly reduced the expression of MMP-1, MMP-3, RANKL, and TNF-α. Transcriptional results suggested that berberine intervention mainly regulated forkhead box O (FOXO) signal pathway, prolactin signal pathway, neurotrophic factor signal pathway, and hypoxia-inducible factor 1 (HIF-1) signal pathway. The effect of berberine on RA was related to the regulation of RAS/mitogen-activated protein kinase/FOXO/HIF-1 signal pathway in RA-FLS cells.Cite this article:  2023;12(2):91-102.