The potential role for berberine, an alkaloid dietary supplement, in mitigating the subclinical pathology and delaying onset of rheumatoid arthritis

Abstract Berberine (BBR), a dietary supplement, is primarily marketed for the alleviation of polycystic ovary syndrome, type II diabetes, and inflammatory bowel disorders, with evidence from successful clinical trials. However, evidence also suggests that BBR might alleviate symptoms of rheumatoid arthritis in vivo, and have a potential prophylactic role from in vitrostudies. We examined BBR’s prophylactic potential for delaying onset of collagen-induced arthritis (CIA) in DBA/1J mice. To induce arthritis, mice were injected with a collagen/CFA emulsion on day 0 and a booster injection of collagen/IFA on day 18. Mice were either treated with 1 mg/kg of BBR daily (CIA+BBR group) or a vehicle control (CIA+PBS) via IP injections from day 0 to day 28, were left untreated (CIA group), or were in a non-arthritic control group. Incidence of arthritis by day 28 in CIA+BBR mice was 40%, compared to 90% in the CIA and CIA+PBS groups. Populations of B cells and T cells from the spleens and draining lymph nodes were examined from random mice across treatment groups during the pre-clinical stage of arthritis (day 14), and from the remaining mice on day 28 when arthritic signs and symptoms were expected to be apparent. Expression of co-stimulatory molecules CD80, CD86, MHC Class II, and CD40 was quantified on CD19+ B cells, and CD40L and CD28 on CD4+/CD3+ T cells. The concentrations of collagen type II-specific IgG2a, IgG1, and total IgG was obtained via ELISA. Finally, leukocyte infiltration into synovial tissue was imaged via confocal microscopy and compared across treatment groups on day 14 and day 28. The results indicate that there may be a potential role for BBR as a prophylactic supplement, although further examination into mechanism of action must be elucidated.