Isoginkgetin protects chondrocytes and inhibits osteoarthritis through NF-κB and P21 signaling pathway

OBJECTIVE: Osteoarthritis (OA) is the most prevalent chronic articular disease in adults. The degree of cartilage degradation and matrix depletion in OA have been substantially connected with chondrocyte inflammatory response. Consequently, pharmacological anti-inflammatory agents provide OA patients a new therapeutic option. Isoginkgetin (IGK), a bioactive bioflavonoid derived from the medicinal herb Ginkgo Biloba, defends against obesity-induced heart diastolic dysfunction and harmful remodeling. Whether IGK has a regulatory effect on OA remains unknown. This study investigated whether IGK could attenuate the progression of OA both in vivo and in vitro. METHODS: Cell Counting Kit-8 (CCK8) was used to measure the vitality of chondrocytes. Mediators of inflammation, anabolism and catabolism were tested by Western blot and RT-PCR. Safranin-O staining, Hematoxylin-Eosin (H&E) staining, immunofluorescence, and Osteoarthritis Research Society International (OARSI) standards were used to assess the severity of OA and the degradation of articular cartilage. The phenotype of cartilage, NF-κB and P21 signaling pathway were measured by Western Blot. The mRNA sequencing was selected to find the differentially expressed genes and potential pathway. Pain of mice was measured by Von Frey hair mechanosensitivity. The senescence level of chondrocyte was SA-β-Gal staining. RESULTS: IGK inhibited catabolism and promoted anabolism after stimulating by IL-1β in vitro. Following destabilization of the medial meniscus (DMM) surgery, administration of IGK significantly reduced OARSI scores and attenuated AGGRECAN and COLLAGEN2 loss, overexpression of MMP3 and articular cartilage deterioration. IGK relieved pain of mice after DMM. Besides, PI3K/AKT/NF-κB, P53, Autophagy, Ferroptosis pathway and reactive oxygen species (ROS), senescence of cartilage were changed after IGK treatment. CONCLUSION: IGK protects articular cartilage and reduces the progression of OA in a mouse model and shows promise as a potential therapeutic strategy for OA.