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.

Automated summary

This study aimed to explore the therapeutic effect and mechanism of berberine on rheumatoid arthritis (RA). It was found that berberine could inhibit the proliferation and adhesion of RA cells and significantly reduce the expression of related factors. Transcriptional results revealed that berberine intervention mainly regulated the FOXO signal pathway, prolactin signal pathway, neurotrophic factor signal pathway, and hypoxia-inducible factor 1 (HIF-1) signal pathway in RA cells.