Chondroprotective and antiarthritic effects of Daphnetin used in vitro and in vivo osteoarthritis models

Aims: Daphnetin (DAP) is a traditional Chinese drug usually used to treat cardiovascular diseases. Studies have confirmed the anti-inflammatory, antioxidant, anti-bacterial and insecticidal, anti-tumor and neuro-protective effects of DAP. However, its anti-arthritic potential remains unexplored. The aim of this study is to investigate the in vitro and in vivo chondroprotective effects of DAP. Main methods: The effect of DAP on primary rabbit chondrocytes was examined using recombinant human IL-1 beta for 24 h. For the in vivo studies, rabbits were randomly divided into groups: a normal control group and osteoarthritis (OA) groups. The OA groups received three different doses of DAP for 4 or 8 weeks. The anti-arthritic effect of DAP was assessed using histopathological examinations, qRT-PCR, western blotting and immunohistochemical analysis. Key findings: Both in vitro and in vivo results indicate that DAP exerts a protective effect against IL-1 beta in chondrocytes. In vitro, DAP inhibits the expression of IL-6, IL-12, MMP-3, MMP-9 and MMP-13, induced by IL-1 beta in rabbit chondrocytes, and stimulates the production of IL-10. The inhibitory effect of DAP on the MMPs is partially regulated by the inhibition of the PI3K/AKT, MAPK and NF-kappa B signaling pathways. The effect of DAP on OA may be attributed to the suppression of inflammatory factor secretion, chondrocyte apoptosis observed by the decrease in pro-apoptotic Caspase-3 and BAX, and the activation of anti-apoptotic BCL-2. Significance: DAP has a broad range of prospects in the treatment of OA, which provides a novel therapeutic strategy for OA.