Honokiol alleviates the degeneration of intervertebral disc via suppressing the activation of TXNIP-NLRP3 inflammasome signal pathway
| Autor: | Jiying Wang, Zhiwei Jie, Kangmao Huang, Xue-Sheng Jiang, Ziang Xie, Jia-Ming Gu, Yu Gu, Shunwu Fan, Pan Tang, Zhi-Jun Hu |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Honokiol Male Nucleus Pulposus Inflammasomes Type II collagen Cell Cycle Proteins Intervertebral Disc Degeneration medicine.disease_cause Biochemistry Antioxidants Lignans Rats Sprague-Dawley 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Physiology (medical) NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Chemistry Biphenyl Compounds Interleukin Inflammasome musculoskeletal system Cell biology Rats 030104 developmental biology medicine.anatomical_structure Apoptosis Carrier Proteins Nucleus 030217 neurology & neurosurgery TXNIP Oxidative stress medicine.drug Signal Transduction |
| Zdroj: | Free radical biologymedicine. 120 |
| ISSN: | 1873-4596 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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