volume 75 issue 5 pages 612-624

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

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
Publication typeJournal Article
Publication date2023-02-28
scimago Q2
wos Q2
SJR0.717
CiteScore6.1
Impact factor3.2
ISSN00223573, 20427158, 23282150
PubMed ID:  36856818
Pharmacology
Pharmaceutical Science
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.

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GOST Copy
Gong Y. et al. Limonin delays the progression of intervertebral disc degeneration in vivo and in vitro: the key role of the MAPK/NF-κB and necroptosis pathways // Journal of Pharmacy and Pharmacology. 2023. Vol. 75. No. 5. pp. 612-624.
GOST all authors (up to 50) Copy
Gong Y., Jiang T., Lu F., Sun J., Xu W., Qiu J., Zhang W., Zheng X., Yang G., Chu B., Ye J., Mi S., Hong Z. Limonin delays the progression of intervertebral disc degeneration in vivo and in vitro: the key role of the MAPK/NF-κB and necroptosis pathways // Journal of Pharmacy and Pharmacology. 2023. Vol. 75. No. 5. pp. 612-624.
RIS |
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RIS Copy
TY - JOUR
DO - 10.1093/jpp/rgac094
UR - https://doi.org/10.1093/jpp/rgac094
TI - Limonin delays the progression of intervertebral disc degeneration in vivo and in vitro: the key role of the MAPK/NF-κB and necroptosis pathways
T2 - Journal of Pharmacy and Pharmacology
AU - Gong, Yuhang
AU - Jiang, Ting
AU - Lu, Fangying
AU - Sun, Jiacheng
AU - Xu, Wangjin
AU - Qiu, Jianxin
AU - Zhang, Weikang
AU - Zheng, Xiaohang
AU - Yang, Guangyong
AU - Chu, Binxiang
AU - Ye, Jiajing
AU - Mi, Shuang
AU - Hong, Zhenghua
PY - 2023
DA - 2023/02/28
PB - Wiley
SP - 612-624
IS - 5
VL - 75
PMID - 36856818
SN - 0022-3573
SN - 2042-7158
SN - 2328-2150
ER -
BibTex |
Cite this
BibTex (up to 50 authors) Copy
@article{2023_Gong,
author = {Yuhang Gong and Ting Jiang and Fangying Lu and Jiacheng Sun and Wangjin Xu and Jianxin Qiu and Weikang Zhang and Xiaohang Zheng and Guangyong Yang and Binxiang Chu and Jiajing Ye and Shuang Mi and Zhenghua Hong},
title = {Limonin delays the progression of intervertebral disc degeneration in vivo and in vitro: the key role of the MAPK/NF-κB and necroptosis pathways},
journal = {Journal of Pharmacy and Pharmacology},
year = {2023},
volume = {75},
publisher = {Wiley},
month = {feb},
url = {https://doi.org/10.1093/jpp/rgac094},
number = {5},
pages = {612--624},
doi = {10.1093/jpp/rgac094}
}
MLA
Cite this
MLA Copy
Gong, Yuhang, et al. “Limonin delays the progression of intervertebral disc degeneration in vivo and in vitro: the key role of the MAPK/NF-κB and necroptosis pathways.” Journal of Pharmacy and Pharmacology, vol. 75, no. 5, Feb. 2023, pp. 612-624. https://doi.org/10.1093/jpp/rgac094.