Pachymic acid suppresses the inflammatory response of chondrocytes and alleviates the progression of osteoarthritis via regulating the Sirtuin 6/NF-κB signal axis

Abstract

Articular cartilage degeneration is a characteristic pathological change of osteoarthritis (OA). Pachymic acid (PA) is an active ingredient found in Poria cocos. Previous studies have shown that PA has anti-inflammatory effects on a variety of diseases. However, the role of PA in OA and its underlying mechanisms has not been clearly elucidated. In this study, we investigated potential protective effect of PA on OA through cell experiments in vitro and animal experiments in vivo. PA inhibited interleukin-1β-induced inflammatory mediator production in chondrocytes, which includes nitric oxide, inducible nitric oxide synthase, prostaglandin E2, cyclooxygenase-2, tumor necrosis factor alpha and interleukin-6. Meanwhile, PA also reversed the up-regulation of matrix metalloproteinase-3 and thrombospondin motifs 5, and the down-regulation of collagen type II and aggrecan in IL-1β-treated chondrocytes. Mechanistically, our findings revealed that PA-mediated overexpression of SIRT6 inhibited the NF-κB signaling pathway. In vivo, PA contributes to improve cartilage damage in the mouse OA model. In summary, PA inhibited IL-1β-induced inflammation and extracellular matrix degeneration by promoting SIRT6 expression and inhibiting the NF-κB signaling pathway, which indicates that PA is beneficial for the treatment of OA.