Loganin inhibits the ROS-NLRP3-IL-1β axis by activating the NRF2/HO-1 pathway against osteoarthritis

Background Loganin is a cyclic enol ether glycoside extracted from Cornus officinalis Siebold & Zucc which has long been used in treatment of OA in traditional Chinese medicine. However, the potential mechanism of Loganin in the treatment of OA is poorly known. Aim of the study: The present study aims to investigate whether Loganin could modulate the ROS-NLRP3-IL-1β axis by activating the NRF2/HO-1 pathway to alleviate osteoarthritis. Methods In vitro, chondrocytes were stimulated with LPS to construct an inflammatory model and treated with LOG. ROS levels were measured using fluorometric analysis. QRT-PCR, Western blot and Immunofluorescence examined the expression of NLRP3 and NRF2. Furthermore, we constructed a mouse osteoarthritis model by DMM surgery. We then assessed the progression of osteoarthritis by Micro-CT, H&E staining and S&F staining and immunohistochemistry. Results Loganin decreased LPS-induced ROS levels in chondrocytes and suppressed the NLRP3 inflammasome activation. Furthermore, LOG activated the NRF2 signaling, and the NRF2 inhibitor ML385 abolished the inhibitory effect of LOG on the NLRP3 inflammasome. In vivo results indicated that LOG reduced the DMM surgery-induced cartilage deterioration and bone flab formation. IHC results showed that LOG reduced the NLRP3 activation and increased the expression of NRF2. Conclusions In conclusion, our study suggested that Loganin inhibits the ROS-NLRP3-IL-1β axis by activating the NRF2/HO-1 pathway, thereby delaying the progression of OA.