Brazilin blocks catabolic processes in human osteoarthritic chondrocytes via inhibition of NFKB1/p50

This study aimed to evaluate the chondroprotective and anti-inflammatory activity of brazilin in human osteoarthritic (OA) cartilage and chondrocytes with particular focus on the nuclear factor-kappa B (NF-κB) pathway. Therefore, brazilin was isolated from Caesalpinia sappan and identified using high performance liquid chromatography (HPLC). The effect of brazilin was assessed in cartilage explants treated with 10 ng/ml interleukin (IL)-1β and 10 ng/ml tumor necrosis factor (TNF)-α using histological and biochemical glycosaminoglycan (GAG) analyses and in primary chondrocytes treated with 10 ng/ml IL-1β using RT-qPCR, ELISA, and Western blot. The involvement of NF-κB signaling was examined using a human NF-κB signaling array and in silico pathway analysis. Brazilin was found to reduce the GAG loss from cartilage explants stimulated with IL-1β and TNF-α. NF-κB pathway analysis in chondrocytes revealed NFKB1/p50 as a central player regulating the anti-inflammatory activities of brazilin. Brazilin suppressed the IL-1β-mediated up-regulation of OA markers and the induction of NFKB1/p50 in chondrocytes. In conclusion, brazilin effectively attenuates catabolic processes in human OA cartilage and chondrocytes—at least in part due to the inhibition of NFKB1/p50—which indicates a chondroprotective potential of brazilin in OA.