Oroxylin A attenuates IL‑1β‑induced inflammatory reaction via inhibiting the activation of the ERK and PI3K/AKT signaling pathways in osteoarthritis chondrocytes

Abstract

Osteoarthritis (OA) is characterized by degradation of the articular cartilage, synovium inflammation, subchondral bone sclerosis and osteophyte formation. OA is the most common degenerative joint disorder among the elderly population. In particular, currently available therapeutic strategies, such as non-steroidal anti-inflammatory drugs (NSAIDs) may cause severe side-effects. Therefore, novel candidate targets for OA therapy are urgently needed. Oroxylin A (OrA) is a natural mono-flavonoid that can be extracted from Scutellariae radix. The present study aimed to investigate the potential effects of OrA on interleukin (IL)-1β-induced chondrocytes inflammatory reactions. The current study performed quantitative PCR, western blotting and cell immunofluorescence to evaluate the effect of Oroxylin A in chondrocyte inflammation. The results demonstrated that OrA significantly attenuated the upregulation of inducible nitric oxide synthase and cyclooxygenase 2 by IL-1β at both protein and mRNA levels. IL-1β-stimulated upregulation of matrix metalloproteinase (MMP)-3 and MMP-13 expression, in addition to disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5 expression, were all inhibited by OrA. Treatment with OrA significantly reversed the degradation of type II collagen and aggrecan by IL-1β. Mechanistically, OrA suppressed the IL-1β induced activation of ERK1/2 and PI3K/AKT signaling pathways. In conclusion, these findings suggest that OrA can serve as a potential therapeutic agent for the treatment of OA.