LAUSR

Abstract Osteoarthritis (OA) is a progressive degenerative disease characterized by irreversible articular cartilage destruction. Butein, a polyphenolic compound isolated from the stem bark of cashews and Rhus verniciflua Stokes, has been reported to have anti‐inflammatory effects. This study aimed to assess the effect of butein on human OA chondrocytes and mice OA models induced by destabilization of the medial meniscus (DMM). In vitro, human OA chondrocytes were pretreated with butein at 10, 50 &mgr;M and subsequently stimulated with IL‐1&bgr; (10 ng/ml) for 24 h. Production of NO, PGE2, TNF‐&agr; and IL‐6 was evaluated by the Griess reaction and ELISAs. The mRNA expression of COX‐2, iNOS, TNF‐&agr;, IL‐6, MMP‐1, MMP‐3, MMP‐13, ADAMTS‐4, ADAMTS‐5, COL‐2 and SOX‐9 were measured by real‐time PCR. The protein expression of COX‐2, iNOS, MMP‐13, COL‐2, SOX‐9, p65 and I&kgr;B‐&agr; were detected by Western blot. P65 nuclear translocation was detected by immunofluorescence. In vivo, the severity of OA was determined by histological analysis. We found that butein significantly inhibited the IL‐1&bgr;‐induced production of NO and PGE2, expression of COX‐2, iNOS, TNF‐&agr;, IL‐6 and MMP‐13, degradation of COL‐2 and SOX‐9 at mRNA and protein levels as well as MMP‐1, MMP‐3, ADAMTS‐4 and ADAMTS‐5 gene expression. Furthermore, butein dramatically suppressed IL‐1&bgr;‐stimulated I&kgr;B‐&agr; degradation and NF‐kB p65 activation. In vivo, the cartilage in butein‐treated mice exhibited less Safranin O loss, cartilage erosion and lower OARSI scores. Butein also reduced subchondral bone plate thickness and alleviated synovitis. Taken together, these findings indicate that butein may be a potential agent in the treatment of OA. Graphical abstract Figure. No Caption available. HighlightsButein inhibited the IL‐1&bgr;‐induced inflammatory mediators in human osteoarthritis chondrocytes.Butein inhibited the IL‐1&bgr;‐induced degradation of type II collagen and SOX‐9 in human osteoarthritis chondrocytes.Butein inhibited the IL‐1&bgr;‐induced I&kgr;B‐&agr; degradation, NF‐kB p65 activation and NF‐&kgr;B p65 nuclear translocation in human osteoarthritis chondrocytes.Butein attenuated the arthritis in mice osteoarthritis models.