Isobavachalcone ameliorates the progression of osteoarthritis by suppressing NF-κB signaling pathway.

Abstract

Isobavachalcone (IBC), an active component isolated from Psoralea corylifolia L., has been used extensively to treat a wide range of inflammation-associated diseases. However, little is known regarding the potential effect of IBC in the treatment of osteoarthritis (OA). The purpose of this research was to investigate the potential therapeutic effectsof IBC on OA by performingin vitroand in vivo experiments. Meanwhile, the underlying mechanism responsibles for that effect was also explored. Primary rat chondrocytes were isolated from the knee cartilage, and then pretreated with various concentrations of IBC followed by stimulation with or without LPS (1µg/ml) for the indicated times. In vitro, the expression levels of iNOS, COX-2, MMP3, MMP13, ADAMTS5, aggrecan, and collagen II were determined by qRT-PCR, western blot, and immunofluorescence staining. In addition, western blot analysis and immunofluorescence were used to assess alterations to the NF-κB signaling pathway. In vivo, an ACLT-induced rat OA model was established in order to determine the protective effect of IBC. The results showed that IBC treatment inhibited the upregulation of inflammatory factors such as iNOS and COX-2 in response to LPS stimulation. Moreover, IBC significantly suppressed the expression of MMP-3, MMP-13, and ADAMTS5 induced by LPS in a dose-dependent manner. Furthermore, the LPS-induced reduction of collagen II and aggrecan was reversed by IBC. Mechanistically, IBC significantly decreased LPS-induced p65 phosphorylation and IκBα degradation as well as suppressed nuclear translocation of p65 in rat chondrocytes as evidenced by western blot analysis and immunofluorescence staining, indicating that IBC effectively inhibited the LPS-induced activation of the NF-κB pathway. In vivo, IBC treatment prevented cartilage degeneration in the ACLT-induced rat model. In summary, our results suggest that IBC may be able to act as a promising therapeutic drug for treating OA.