Marein ameliorates the progression of osteoarthritis: An in vitro and in vivo studies

Osteoarthritis (OA) is a prevalent, degenerative joint disease that requires effective treatments to prevent its progression. Therefore, the development of novel therapeutic strategies to address this unmet clinical challenge is paramount. Marein (MA), the principal active compound of Coreopsis tinctoria Nutt, exhibits anti-inflammatory and anti-oxidant properties in various diseases, indicating its potential as a therapeutic agent for OA. In this study, we assessed the ability of marein to mitigate the inflammatory response in OA and reverse cartilage degradation. The results demonstrated that MA exerted a concentration -dependent effect (10, 25, 50 μM), facilitating the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), reversing the suppression of nuclear factor kappa B (NF-κB) activation, and mitigating the inflammatory response, ultimately alleviating joint cartilage damage. In cellular assays, MA (10, 25, 50 μM) markedly decreased the expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), matrix metalloproteinase-13 (MMP-13) and a metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), simultaneously decreasing reactive oxygen species production by enhancing Nrf2 nuclear translocation. Furthermore, in animal models, MA (50 μM) significantly improved knee joint cartilage damage and effectively reduced OA progression. Further studies are needed to determine the long-term safety and therapeutic potential of MA and to expand its application scope. Moreover, preclinical studies are required to evaluate the efficacy of MA in humans. Overall, MA is a promising therapeutic candidate and may be an effective treatment for patients with OA.