Orientin inhibits inflammation in chondrocytes and attenuates osteoarthritis through Nrf2/NF-κB and SIRT6/NF-κB pathway.

Abstract

Osteoarthritis (OA) is the most common form of degenerative joint disease. and chondrocyte inflammation plays an important role in OA development. The natural flavonoid compound Orientin (Orientin) has anti-inflammatory bioactive properties in the treatment of various diseases. Studies have not explored whether Orientin modulates OA progression. In our study, we researched the anti-osteoarthritis effects of Orientin, as well as the potential mechanisms that underlie its action. Effects of Orientin on OA were detected in chondrocytes and OA mouse model. Effects of Orientin on murine chondrocytes treated with interleukin-1β (IL-1β) were evaluated using qPCR, western blot analysis, ELISA and immunofluorescent staining in vitro. In vivo, We established a standard OA model by performing the destabilized medial meniscus (DMM) surgery on C57BL/6 mice, and assessed healing effect of Orientin by X-ray imaging, histopathological analysis, immunohistochemical staining. A significant suppression in IL-1β-mediated pro-inflammatory mediators and the degradation of cartilage extracellular matrix (ECM) was observed in vitro after a treatment with Orientin. In addition, Orientin abrogated DMM surgery induced cartilage degradation in mice. Mechanistic studies showed that Orientin suppressed OA development by downregulating activation of NF-κB by activating Nrf2/HO-1 axis and SIRT6 signaling pathway. The study indicates that Orientin inhibits inflammation of chondrocytes and ECM degradation, which are key contributors to OA progression. Effects of Orientin are mediated through Nrf2/NF-κB and the SIRT6/NF-κB pathways. These results provide evidence that Orientin serves as a potentially viable compound for the treatment of OA. This article is protected by copyright. All rights reserved.