Berberine Inhibits the Gene Expression and Production of Proinflammatory Cytokines by Mononuclear Cells in Rheumatoid Arthritis and Healthy Individuals

Objective: Rheumatoid arthritis (RA) is the most prevalent autoimmune arthritis. Berberine is an alkaloid isolated from Berberis vulgaris, and its anti-inflammatory effect has been identified. Methods: Twenty newly diagnosed RA patients and 20 healthy controls participated. Peripheral mononuclear cells were prepared and stimulated with bacterial lipopolysachharide (LPS,1 μg/ml), exposed to different concentrations of berberine (10 and 50μM) and dexamethasone (10-7 M) as a reference. The toxicity of compounds was evaluated by WST-1 assay. The expression of TNF-α and IL-1β was determined by quantitative real-time PCR. Protein level of secreted TNF-α and IL-1β was measured by using ELISA. Results: Berberine did not have any toxic effect on cells, whereas Lipopolysaccharide (LPS) stimulation caused a noticeable rise in TNF-α and IL-1β production. Berberine markedly downregulated the expression of both TNF-α and IL-1β, and inhibited TNF-α and IL-1β secretion from LPS-stimulated PBMCs. Discussion: This study provided a molecular basis for anti-inflammatory effect of berberine on human mononuclear cells through the suppression of TNF-a and IL-1secretion. Our findings highlighted the significant inhibitory effect of berberine on proinflammatory responses of mononuclear cells from rheumatoid arthritis individuals, which may be responsible for antiinflammatory property of Barberry. We observed that berberine at high concentration exhibited anti-inflammatory effect in PBMCs of both healthy and patient groups by suppression of TNF-a and IL-1cytokines at both mRNA and protein levels. Conclusion: Berberine may inhibit the gene expression and production of pro-inflammatory cytokines by mononuclear cells in rheumatoid arthritis and healthy individuals without affecting cell viability. Future studies with a larger sample size are needed to prove the idea.