Asperuloside-Mediated Activation of Nrf2 Inhibits the NF-κB Pathway and Suppresses Osteoarthritis Progression.

Abstract

As a widespread chronic degenerative joint disease that predominantly affects elderly populations worldwide, osteoarthritis (OA) is pathologically defined by the gradual breakdown of extracellular matrix (ECM), cellular apoptosis, and inflammatory processes. Asperuloside (ASP), an iridoid glycoside compound, demonstrates broad bioactivity encompassing inflammation modulation and oxidative stress mitigation across disease models. Nevertheless, the potential of ASP for OA treatment and its associated molecular mechanisms have not yet been completely deciphered. This investigation sought to clarify the therapeutic mechanisms of ASP in OA, thus providing experimental evidence supporting its potential as a novel disease-modifying treatment. Western blotting and immunofluorescent assay were utilized to explore ASP's protective role against IL-1β-mediated damage in primary chondrocytes in vitro. Healing effect of ASP was evaluated via micro-CT imaging, histopathological analysis and immunohistochemical staining were conducted using a rat model with destabilized medial meniscus (DMM) in vivo. ASP reversed IL-1β-induced pathological effects, including ECM degradation, inflammatory mediator secretion, and cellular apoptosis in chondrocytes. In the DMM rat model, ASP attenuated cartilage degeneration. Mechanistically, it suppressed OA progression via Nrf2/HO-1/NQO1 pathway signaling, suppressing both NF-κB activation and ROS accumulation. ASP alleviated OA progression by inhibiting chondrocyte apoptosis, inflammatory responses, and ECM degradation in both cellular and DMM rat models through Nrf2-mediated suppression of NF-κB signaling. Collectively, ASP may be a promising disease-modifying drug for OA.