Ginkgetin Alleviates Intervertebral Disc Degeneration by Inhibiting Apoptosis, Inflammation, and Disturbance of Extracellular Matrix Synthesis and Catabolism via Inactivation of NLRP3 Inflammasome

BackgroundApoptosis, inflammation, and the extracellular matrix (ECM) synthesis and catabolism are compromised with intervertebral disc degeneration (IDD). Ginkgetin (GK) has been demonstrated to alleviate several diseases; however, its effect on IDD remains unknown.MethodsThe nucleus pulposus cells (NPCs) were stimulated with interleukin (IL)-1 beta to construct the IDD models in vitro. Rats were used for the construction of the IDD models in vivo via the fibrous ring puncture method. The effect and mechanism of GK on IDD were determined by cell counting kit-8 (CCK-8), flow cytometry, western blot, real-time quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), hematoxylin and eosin (HE) and safranine O staining, and immunohistochemistry (IHC) assays, respectively.ResultsGK increased the cell viability and upregulated the expressions of anti-apoptosis and ECM synthesis markers in NPCs treated with IL-1 beta. GK also decreased apoptosis rate, and downregulated the expressions of proteins related to pro-apoptosis, ECM catabolism, and inflammation in vitro. Mechanically, GK reduced the expression of nucleotide binding oligomeric domain like receptor protein 3 (NLRP3) inflammasome-related proteins. Overexpression of NLRP3 reversed the effect of GK on the proliferation, apoptosis, inflammation, and ECM degradation in IL-1 beta-induced NPCs. Moreover, GK attenuated the pathological manifestations, inflammation, ECM degradation, and NLRP3 inflammasome expression in IDD rats.ConclusionGK suppressed apoptosis, inflammation, and ECM degradation to alleviate IDD via the inactivation of NLRP3 inflammasome.