Asiaticoside ameliorates osteoarthritis progression through activation of Nrf2/HO-1 and inhibition of the NF-κB pathway

Osteoarthritis has become the fourth cause of disability in the world and its occurrence and development are caused by apoptosis and extracellular matrix (ECM) degradation of chondrocytes. Asiaticoside (ASI) is a triterpene saponin compound obtained from Centella Asiatica and has anti-inflammatory and anti-apoptotic effects in various diseases. However, its effects on OA are not clear. In this study, we reported that ASI has a protective effect on the occurrence and progression of OA in vivo and in vitro, and demonstrated its potential molecular mechanism. In vitro, ASI treatment inhibited the release of pro-apoptotic factors induced by TBHP and promoted the release of the anti-apoptotic proteins. In addition, ASI promotes the expression of Aggrecan and Collagen II, while inhibiting the expression of thrombospondin motifs 5 (ADAMTS5) and matrix metalloproteinase-13 (MMP-13), which causes extracellular matrix (ECM) degradation. Mechanistically, ASI exerts its anti-apoptotic effect by activating the Nrf2/HO-1 pathway and preventing p65 from binding to DNA. Similarly, in vivo, ASI has been shown to have a protective effect in a mouse OA model. The conclusion is that our research shows that ASI can be used as a potential drug for the treatment of OA.