2. Academic Validation
  3. Limonin delays the progression of intervertebral disc degeneration in vivo and in vitro: the key role of the MAPK/NF-κB and necroptosis pathways

Limonin delays the progression of intervertebral disc degeneration in vivo and in vitro: the key role of the MAPK/NF-κB and necroptosis pathways

  • J Pharm Pharmacol. 2023 Feb 28;rgac094. doi: 10.1093/jpp/rgac094.
Yuhang Gong 1 2,  Ting Jiang 1 2,  Fangying Lu 1 2,  Jiacheng Sun 1 2,  Wangjin Xu 3,  Jianxin Qiu 1 2,  Weikang Zhang 2 4,  Xiaohang Zheng 1 2,  Guangyong Yang 1 2,  Binxiang Chu 1 2,  Jiajing Ye 1 2,  Shuang Mi 1 2,  Zhenghua Hong 1 2
Affiliations

Affiliations

  • 1 Department of Orthopaedics, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, Zhejiang, China.
  • 2 Bone Development and Metabolism Research Center, Taizhou Hospital of Zhejiang Province, Linhai, Zhejiang, China.
  • 3 Department of General Surgery, Taizhou Hospital Affiliated to Wenzhou Medical University, Linhai, Zhejiang, China.
  • 4 Guangzhou Laboratory, Huazhong University of Science and Technology, Guangzhou, Guangdong, China.
PMID: 36856818 DOI: 10.1093/jpp/rgac094
Abstract

Objectives: Limonin has received significant attention due to its multiple biological effects, intervertebral disc degeneration (IDD) is also of interest due to the high prevalence of this disease. In this study, we determined the effects of limonin on IDD and the underlying mechanism of action to find novel ways to treat IDD.

Methods: An IL-1β-induced cell inflammation model and a lumbar instability model inducing IDD were established to assess the progression of IDD with or without limonin treatment. We further evaluated MAPK/NF-κB and Necroptosis pathways and alterations in the extracellular matrix specific within the disc.

Key findings: Limonin suppresses inflammation in the nucleus pulposus in vitro by reducing the production of pro-inflammatory markers such as iNOS and COX-2. Limonin reduced the activation of the MAPK/NF-κB signalling pathway and the RIP1/RIP3/MLKL Necroptosis pathway in the NP cells. Moreover, limonin delays the IDD progression in the lumbar instability model.

Conclusions: Limonin could potentially delay IDD by inhibiting NP cell Necroptosis and modulating peripheral matrix proteins within the intervertebral disc and is a potential pharmacological research direction for the therapy in patients with IDD.

Keywords

Intervertebral disc degeneration; MAPK; NK-κB; inflammation; limonin; necroptosis.

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