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

Abstract

ABSTRACT 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.