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

China Aims Rheumatoid arthritis (RA) is a common chronic immune disease. Berberine, as its main ac-tive 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.Methods Cell Counting Kit -8 was used to evaluate the effect of berberine on the proliferation of RA fibroblast -like synoviocyte (RA -FL S) cells. The effect of berberine on matrix metalloprotein-ase (MMP)- 1, MMP- 3, receptor activator of nuclear factor kappa-Beta ligand (RANKL), tumour necrosis factor alpha (TNF-alpha), and other factors was determined by enzyme-linked immu-noassay (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.Results Berberine inhibited proliferation and adhesion of RA -FL S cells, and significantly reduced the expression of MMP- 1, MMP- 3, RANKL, and TNF-alpha. 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.Conclusion The effect of berberine on RA was related to the regulation of RAS/mitogen-activated protein kinase/FOXO/HIF- 1 signal pathway in RA -FL S cells.