Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 120, Issue -, Pages 368-379Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2018.04.008
Keywords
Intervertebral disc degeneration; Honokiol; TXNIP; NLRP3; ROS
Funding
- National Natural Science Foundation of China [81472064, 81501912, 81672150, 81672208, 81601924, 81601925]
- Natural Science Foundation of Zhejiang Province [Z15H060002, LY16H060004, LY16H060002]
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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 NFkB 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-1 beta. 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 - 1 beta 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.
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