Berberine Prevents Bone and Cartilage Destruction and Influences Cell Senescence in Experimental Arthritis

Abstract

Background: Berberine (BB) is a protoberberine alkaloid with a wide spectrum of pharmacological activities considered to be a selective Janus kinase (Jak)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 cartilage and bone destruction, and on 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 haematoxylin and eosin (H&E), toluidine blue and Sudan Black B (SBB) staining. Bone marrow (BM) cells were shifted to osteoblast differentiation and alkaline phosphatase (ALP) positive cells were determined together with ALP activity in the cell lysates. Calvarial osteoblast generation was determined by von Cossa staining. Results: Berberine decreased cartilage and bone erosion. The loss of glycosaminoglycans (GAGs) was lower in BB-treated group (72.0 +/- 2.9% in ZIA mice vs 25.7 +/- 2.2 in BB group). BB inhibited the generation of senescent cells and decreased the ALP activity of these cells (0.550 +/- 0.006 for non-arthritic, 1.725.8 +/- 0.110 for ZIA and 0.750 +/- 0.0.064 for ZIA+BB). Conclusion: Berberine showed potential anti-arthritic properties in a model of erosive RA perspective for administration in joint disorders.