Andrographolide mitigates IL-1β-induced human nucleus pulposus cells degeneration through the TLR4/MyD88/NF-κB signaling pathway

Intervertebral disc degeneration (IDD) is a multifactorial disease with few efficacious clinical drugs, which has been demonstrated to be associated with nucleus pulposus (NP) cells apoptosis and degeneration of the extracellular matrix (ECM). Interleukin (IL)-1β, a common proinflammatory cytokine, is considered to be one of key regulators in IDD development. Andrographolide (AG), extracted from Andrographis paniculata, has been suggested to possess marked anti-inflammatory properties. However, the effects of AG on IDD has not been well explored. The present study aimed to investigate the effects and the mechanisms of AG on IDD in human NP cells. NP cells were treated with IL-1β in the absence or presence of AG to investigate the effects on cell viability, cellular apoptosis, production of ECM and matrix metalloproteinase (MMP)-3, MMP-9 and MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4 and ADAMTS-5. It was identified that IL-1β-induced NP cellular apoptosis was significantly inhibited by AG treatment. Furthermore, AG mitigated the IL-1β-induced degeneration of the ECM, which was paralleled by a decrease in MMPs and ADAMTS levels. In addition, AG exhibited marked inhibitory properties against the activation of Toll-like receptors (TLRs), Myeloid differentiation factor 88 (MyD88) and the nuclear translocation of Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Taken together, these results demonstrated that AG treatment mitigated IL-1β-induced NP cells degeneration through the TLR4/MyD88/NF-κB signaling pathway, and suggested that AG may be a potential agent for IDD prevention and therapy.