Plantamajoside suppresses the activation of NF-κB and MAPK and ameliorates the development of osteoarthritis

•This is the first report on the potential therapeutic effect of plantamajoside on osteoarthritis.•In vitro analyses, plantamajoside inhibits NF-κB (nuclear factor kappa-B) and MAPK (mitogen-activated protein kinase) signaling pathways, promoting chondrocyte repair.•In-vivo study demonstrated that plantamajoside could ameliorate progression in the mouse osteoarthritis model. Osteoarthritis (OA) is a common degenerative bone and joint disorder characterized by progressive cartilage degeneration and secondary synovial inflammation. It is a common chronic joint disorder that affects people of all ages (especially the old). Plantamajoside is a phenylpropanoside derived from plantain. It has a variety of biological properties, including antioxidant, anti-malignant cell proliferation, and anti-inflammatory properties. In this study, the latent mechanism of plantamajoside was explored by slowing the in-vivo and in-vitro progression of osteoarthritis. The results revealed that plantamajoside pre-conditioning inhibited IL-1β induced pro-inflammatory factors like COX-2, iNOS, IL-6, and TNF-α. Moreover, plantamajoside also reversed the IL-1 β mediated type II collagen and aggrecan degradation within the extracellular matrix (ECM). The protective effects of plantamajoside have been attributed to the inhibition of both MAPK and NF-κB pathways. Furthermore, our in-vivo research found that plantamajoside could slow the progression of OA in mice. Finally, all findings point to plantamajoside as a potential anti-OA therapeutic candidate.