Ganoderic Acid A alleviates the degeneration of intervertebral disc via suppressing the activation of TLR4/NLRP3 signaling pathway

As a multifactorial disease, intervertebral disc degeneration (IVDD) causes many spinal-related diseases, which causes disability in the workforce and heavy social costs all over the world. Recently, Ganoderic Acid A (GAA) has been reported to play many pharmacological effects. However, its effect on IVDD remains unclear. In the present study, our study determined that GAA significantly inhibited H₂O₂ induced apoptosis, release of inflammatory cytokines and oxidative stress mediators in the nucleus pulposus (NP) cells. Moreover, GAA also suppressed H₂O₂ induced major matrix degrading proteases (MMP-3, MMP-13, ADAMTS4 and ADAMTS5) associated with NP degradation. Additionally, we found NP protective ability of GAA by up-regulating extra cellular matrix anabolic factors like type II collagen (Col II) and aggrecan in NP cells. Furthermore, we also demonstrated that GAA suppressed the activation of TLR4/NLRP3 in H₂O₂-stimulated NP cells. Thus, our results demonstrate that GAA inhibited the H₂O₂ induced apoptosis, oxidative stress, and inflammatory responses through the depression of TLR4/NLRP3 signaling axis. GAA possess NP protective properties and may be of value in suppressing the pathogenesis of IVDD.