Ganoderic Acid A Attenuates IL-1β-Induced Inflammation in Human Nucleus Pulposus Cells Through Inhibiting the NF-κB Pathway.

Abstract

Intervertebral disc (IVD) degeneration is a major cause of low back pain associated with several pathological changes in the IVD, including dysfunction of nucleus pulposus (NP) cells. Ganoderic Acid A (GAA), one of triterpenoid extracts of Ganoderma lucidum (G. lucidum), has been reported to possess anti-inflammatory effect. In the current study, we aimed to evaluate the effect of Ganoderic Acid A (GAA) on the interleukin-1β (IL-1β)-induced inflammation in human NP cells. Our results showed that the IL-1β-stimulated production of inflammatory mediators including nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 were suppressed by GAA. In addition, treatment of NP cells with GAA significantly inhibited the production of inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in IL-1β-stimulated human NP cells. GAA improved the reduced expression levels of extracellular matrix (ECM) proteins, collagen II and aggrecan in IL-1β-stimulated human NP cells. GAA also alleviated IL-1β-induced the levels of matrix metalloproteinase (MMP)-3 and MMP-13. Furthermore, GAA inhibited the IL-1β-induced upregulation of the phosphorylation of p65 and downregulation of IκBα. Taken together, these findings indicated that GAA alleviated IL-1β-induced inflammation and ECM degradation in NP cells through regulating NF-κB pathway.