Influence of Berberine on Megakaryocyte and Apoptotic Cell Populations in Erosive Arthritis

Background: Berberine (BB) is a protoberberine alkaloid with a wide spectrum of pharmacological activities considered to be a Janus kinase (Jak)2/3 inhibitor. Nevertheless, the mechanisms of berberine’s actions on joint inflammation have not been well clarified. Aim: This study evaluated the effect of berberine on the processes of apoptosis and on the generation of senescent cells. Methodology: The experiments were conducted in a murine model of erosive arthritis induced by intra-articular (i.a.) injection of zymosan (zymosan-induced arthritis, ZIA). Histopathologic changes were evaluated by Sudan Black B (SBB) staining. Bone marrow (BM) cell differentiation was assessed by TRAP and -galactosidase staining. The apoptosis and the expression of Bcl-2 and Bax was determined by flowcytometry. Results: Berberine decreased the generation of apoptotic and senescent cells in BM and bone, and lowered TRAIL-induced osteoclast formation. The alkaloid did not change the expression of anti-apoptotic BcL-2 and increased the expression of pro-apoptotic Bax in synovial cells. Berberine inhibited the elevation of megakaryocyte number in BM. Conclusion: Berberine limited the accelerated generation of apoptotic and senescent cells in arthritic mice that may result in amelioration of joint inflammation.