Intervertebral disc degeneration (IVDD) is a multifactorial disease and responsible
for many spine related disorders, causes disability in the workforce and heavy social
costs all over the world. Honokiol, a low molecular weight natural product, could
penetrate into and distribute in IVDs to achieve therapeutic effect in a rat tail
model. Therefore, the present study was undertaken to examine the antiinflammatory,
antioxidation and IVD-protective effect of honokiol using nucleus pulposus cells and
investigate its mechanisms to provide a new basis for future clinical treatment of
IVDD. In the current study, we demonstrated that honokiol inhibits the H2O2-induced
apoptosis (caspase-9, caspase-3, and bax), levels of oxidative stress mediators (ROS,
MDA), expression of inflammatory mediators (Interleukin-6, COX-2, and iNOS), major
matrix degrading proteases (MMP-3, MMP-13, ADAMTS5, and ADAMTS4) associated with nucleus
pulposus degradation. Furthermore, we found nucleus pulposus protective ability of
honokiol by up-regulating extra cellular matrix anabolic factors like type II collagen
(Col II) and SOX9 in nucleus pulposus. We also found that honokiol suppressed the
phosphorylation of NF-kB and JNK, and activation of TXNIP-NLRP3 inflammasome in H2O2-stimulated
nucleus pulposus cells, thereby inhibiting the activation of downstream inflammatory
mediators such as Interleukin-1β. Furthermore, honokiol showed a cartilage protective
effect in the progression of IVDD in a rat model induced by puncture. Thus, our results
demonstrate that honokiol inhibited the H2O2 induced apoptosis, oxidative stress,
and inflammatory responses through the depression of TXNIP/NLRP3/caspase-1/ Interleukin
- 1β signaling axis and the activation of NF-kB and JNK. Honokiol possess nucleus
pulposus protective properties and may be of value in suppressing the pathogenesis
of IVDD.