casticin and Osteoarthritis

Casticin, a flavonoid isolated from Vitex trifolia, has been shown to have anti-inflammatory and antitumor effects in previous studies. Osteoarthritis (OA) is a disease based on degenerative pathological changes. The disease process is often accompanied by inflammatory pathological changes. However, there is no safe and effective drug for prevention and treatment. In the present study, we aimed to clarify the role of casticin in the murine model of destabilization of the medial meniscus (DMM). Male BALB/c mice were randomly divided into three groups: Sham, DMM-induced OA treated with vehicle, and DMM-induced OA treated with casticin. Our results indicated that the casticin treatments markedly reduced the destruction of cartilage and OARSI grades compared with those of the vehicle-treated mice. The levels of matrix metalloproteinase-13 (MMP13) in cartilage were also significantly reduced in the casticin-treated mice. Casticin also significantly regulated oxidative stress and reduced inflammation in the cartilage of mice with OA. These results suggest that casticin prevents the development of posttraumatic OA in mice. Consequently, decreased reactive oxygen species levels and suppressed proinflammatory cytokine production were confirmed in casticin-treated IL-1β-stimulated ADTC5 cells. After casticin treatment, the NF-κB signaling pathway was significantly inhibited in the cells. It can be concluded that casticin can alleviate arthritis-related cartilage degeneration by inhibiting ROS-mediated NF-κB signaling pathway in vitro and in vivo.

Topics: Animals; Cartilage, Articular; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Flavonoids; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Osteoarthritis; Random Allocation; Reactive Oxygen Species; Signal Transduction

Casticin, an active compound isolated from Vitex rotundifolia L., was reported to possess anti-inflammatory activity. However, the effect of casticin on inflammatory response in human osteoarthritis (OA) chondrocytes remains unclear. In the current study, we examined the anti-inflammatory effects of casticin on chondrocytes exposed to interleukin-1β (IL-1β). Our results demonstrated that casticin treatment significantly improved cell viability in chondrocytes exposed to IL-1β. Casticin significantly inhibited IL-1β-induced NO and PGE2 production, and iNOS and COX-2 expression in human OA chondrocytes. It also suppressed the levels of TNF-α and IL-6, as well as decreased production of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 in IL-1β-stimulated chondrocytes. Furthermore, casticin prevented IL-1β-induced NF-κB activation in chondrocytes. Taken together, these findings showed that casticin attenuates inflammatory responses in chondrocytes stimulated with IL-1β, possibly through the NF-κB signaling pathway. Thus, casticin may serve as a potential anti-inflammatory agent in the treatment of OA.

Topics: ADAMTS Proteins; Cell Survival; Chondrocytes; Cyclooxygenase 2; Cytoprotection; Dinoprostone; Flavonoids; Gene Expression Regulation, Enzymologic; Humans; Inflammation; Interleukin-1beta; Interleukin-6; Matrix Metalloproteinases; Nitric Oxide; Nitric Oxide Synthase Type II; Osteoarthritis; Signal Transduction; Transcription Factor RelA; Tumor Necrosis Factor-alpha