The Function And Regulative Mechanism Of Honokiol In Nucleus Pulposus Degeneration

Objective:To evaluate the role of Honokiol in the degeneration of the nucleus pulposus and to explore the mechanism of related function.Methods:The activity of cells,apoptosis,the level of SOD and MDA,inflammatory mediators,extracellular matrix,TXNIP/NLRP3 inflammasome axis,and potential signal pathway were evaluated in nucleus pulposus cells.And the effect of honokiol was checked in a rat IVDD model induced by puncture.The mRNA expression of pro-inflammatory cytokines(iNOS,COX-2 and IL-6),metalloproteinases,aggrecanases,TXNIP,NLRP3 inflammasomes,caspase-1,and IL-1? was determined by real-time polymerase chain reaction(PCR)analysis.The protein expression of the above genes and signal pathways were detected by western blot analysis.Results:Our results showed honokiol suppressed the expression of caspase-9,caspase-3 and bax induced by H2O2 in nucleus pulposus cells,and restored the activity of cells.Then,we found that honokiol exhibit potent anti-inflammatory effects through the suppression of inflammatory mediators(IL-6 and iNOS)in nucleus pulposus cells,and restored the balance between the anabolic and catabolic processes by up-regulating Col II and SOX9 and down-regulating MMP-3,MMP-13,ADAMTS-5,and ADAMTS-4.What's more,H2O2 treatment significantly increased the ROS production in nucleus pulposus cells whereas,pretreatment of cells with honokiol significantly suppressed the H2O2-induced generation of ROS.Results indicated that the activation of TXNIP/NLRP3 inflammasome and the cleavage of caspase-1 induced by H2O2 can be attenuated by honokiol through inhibition of NF-kB and JNK signaling.In addition,MRI evalution showed honokiol could not reverse IVDD progression,but it delayed the progression of IVDD in vivo.Conclusions:Honokiol,a small molecular weight natural product,inhibits the H2O2-induced apoptosis,levels of oxidative stress,expression of inflammatory mediators,major proteases associated with degradation.Honokiol exerted the protective effect may through suppressing the phosphorylation of NF-?B and JNK,and activation of TXNIP/NLRP3 inflammasome in H2O2-stimulated nucleus pulposus cells,thereby inhibiting the activation of downstream inflammatory mediators such as IL-1?.Thus,our results suggest that honokiol possess nucleus pulposus protective properties and may be of value in suppressing the pathogenesis of IVDD.