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Sinomenine Ameliorates IL-1β-Induced Intervertebral Disc Degeneration in Rats Through Suppressing Inflammation and Oxidative Stress via Keap1/Nrf2/NF-κB Signaling Pathways

PURPOSE: To investigate the molecular mechanism underlying the inhibitory effect of sinomenine (SN) on interleukin-1β (IL-1β)-induced apoptosis in nucleus pulposus cells (NPCs), and to evaluate the potential role of SN in preventing intervertebral disk degeneration (IDD). METHODS: The Rat NPCs were...

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Autores principales: Lu, Gongbiao, Zhang, Cunxin, Li, Kang, Gao, Kai, Fu, Maoqing, Lyu, Chaoliang, Quan, Zhengxue
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10596063/
https://www.ncbi.nlm.nih.gov/pubmed/37881650
http://dx.doi.org/10.2147/JIR.S430423
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author Lu, Gongbiao
Zhang, Cunxin
Li, Kang
Gao, Kai
Fu, Maoqing
Lyu, Chaoliang
Quan, Zhengxue
author_facet Lu, Gongbiao
Zhang, Cunxin
Li, Kang
Gao, Kai
Fu, Maoqing
Lyu, Chaoliang
Quan, Zhengxue
author_sort Lu, Gongbiao
collection PubMed
description PURPOSE: To investigate the molecular mechanism underlying the inhibitory effect of sinomenine (SN) on interleukin-1β (IL-1β)-induced apoptosis in nucleus pulposus cells (NPCs), and to evaluate the potential role of SN in preventing intervertebral disk degeneration (IDD). METHODS: The Rat NPCs were cultured in vitro and identified using Hematoxylin-Eosin (HE) staining, toluidine blue staining, and immunofluorescence analysis. NPCs were pretreated with or without SN, then induced with IL-1β to assess cell viability, ROS levels, apoptotic rates, and wound healing ability. Relevant protein expression was detected using Elisa, qPCR and Western Blot techniques. NPCs were pretreated with SN, either alone or in combination with Nrf2-IN-1 or SC, before being induced to undergo apoptosis by IL-1β. Apoptosis was detected using Hoechst staining, while qPCR and Western Blot techniques assessed protein expression. Rat caudal intervertebral discs were induced with IDD, with or without SN injection, and then co-injected with IL-1β. The levels of IDD were evaluated using HE staining and modified saffron-O-fix green cartilage staining. Relevant protein expression was detected using Elisa, qPCR, and Western Blot techniques. RESULTS: IL-1β significantly reduced NPC activity, induced ROS accumulation and apoptosis, decreased cell healing rate, promoted the expression and secretion of inflammatory factors, and inhibited extracellular matrix synthesis. However, pretreatment with SN effectively reversed these effects. Inhibition of the Keap1/Nrf2 signaling pathway or activation of the NF-κB signaling pathway significantly attenuated the cytoprotective effects of SN and increased apoptosis. Acupuncture combined with IL-1β injection markedly induced intervertebral disc degeneration in rat caudal spine, upregulated inflammatory factors expression and secretion, and downregulated extracellular matrix synthesis. SN intervention notably enhanced antioxidant enzyme expression and reversed these outcomes. CONCLUSION: SN can prevent IL-1β-induced apoptosis of NPCs and ameliorate IDD by activating the Keap1/Nrf2 pathway and inhibiting the NF-κB signaling pathway.
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spelling pubmed-105960632023-10-25 Sinomenine Ameliorates IL-1β-Induced Intervertebral Disc Degeneration in Rats Through Suppressing Inflammation and Oxidative Stress via Keap1/Nrf2/NF-κB Signaling Pathways Lu, Gongbiao Zhang, Cunxin Li, Kang Gao, Kai Fu, Maoqing Lyu, Chaoliang Quan, Zhengxue J Inflamm Res Original Research PURPOSE: To investigate the molecular mechanism underlying the inhibitory effect of sinomenine (SN) on interleukin-1β (IL-1β)-induced apoptosis in nucleus pulposus cells (NPCs), and to evaluate the potential role of SN in preventing intervertebral disk degeneration (IDD). METHODS: The Rat NPCs were cultured in vitro and identified using Hematoxylin-Eosin (HE) staining, toluidine blue staining, and immunofluorescence analysis. NPCs were pretreated with or without SN, then induced with IL-1β to assess cell viability, ROS levels, apoptotic rates, and wound healing ability. Relevant protein expression was detected using Elisa, qPCR and Western Blot techniques. NPCs were pretreated with SN, either alone or in combination with Nrf2-IN-1 or SC, before being induced to undergo apoptosis by IL-1β. Apoptosis was detected using Hoechst staining, while qPCR and Western Blot techniques assessed protein expression. Rat caudal intervertebral discs were induced with IDD, with or without SN injection, and then co-injected with IL-1β. The levels of IDD were evaluated using HE staining and modified saffron-O-fix green cartilage staining. Relevant protein expression was detected using Elisa, qPCR, and Western Blot techniques. RESULTS: IL-1β significantly reduced NPC activity, induced ROS accumulation and apoptosis, decreased cell healing rate, promoted the expression and secretion of inflammatory factors, and inhibited extracellular matrix synthesis. However, pretreatment with SN effectively reversed these effects. Inhibition of the Keap1/Nrf2 signaling pathway or activation of the NF-κB signaling pathway significantly attenuated the cytoprotective effects of SN and increased apoptosis. Acupuncture combined with IL-1β injection markedly induced intervertebral disc degeneration in rat caudal spine, upregulated inflammatory factors expression and secretion, and downregulated extracellular matrix synthesis. SN intervention notably enhanced antioxidant enzyme expression and reversed these outcomes. CONCLUSION: SN can prevent IL-1β-induced apoptosis of NPCs and ameliorate IDD by activating the Keap1/Nrf2 pathway and inhibiting the NF-κB signaling pathway. Dove 2023-10-20 /pmc/articles/PMC10596063/ /pubmed/37881650 http://dx.doi.org/10.2147/JIR.S430423 Text en © 2023 Lu et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Lu, Gongbiao
Zhang, Cunxin
Li, Kang
Gao, Kai
Fu, Maoqing
Lyu, Chaoliang
Quan, Zhengxue
Sinomenine Ameliorates IL-1β-Induced Intervertebral Disc Degeneration in Rats Through Suppressing Inflammation and Oxidative Stress via Keap1/Nrf2/NF-κB Signaling Pathways
title Sinomenine Ameliorates IL-1β-Induced Intervertebral Disc Degeneration in Rats Through Suppressing Inflammation and Oxidative Stress via Keap1/Nrf2/NF-κB Signaling Pathways
title_full Sinomenine Ameliorates IL-1β-Induced Intervertebral Disc Degeneration in Rats Through Suppressing Inflammation and Oxidative Stress via Keap1/Nrf2/NF-κB Signaling Pathways
title_fullStr Sinomenine Ameliorates IL-1β-Induced Intervertebral Disc Degeneration in Rats Through Suppressing Inflammation and Oxidative Stress via Keap1/Nrf2/NF-κB Signaling Pathways
title_full_unstemmed Sinomenine Ameliorates IL-1β-Induced Intervertebral Disc Degeneration in Rats Through Suppressing Inflammation and Oxidative Stress via Keap1/Nrf2/NF-κB Signaling Pathways
title_short Sinomenine Ameliorates IL-1β-Induced Intervertebral Disc Degeneration in Rats Through Suppressing Inflammation and Oxidative Stress via Keap1/Nrf2/NF-κB Signaling Pathways
title_sort sinomenine ameliorates il-1β-induced intervertebral disc degeneration in rats through suppressing inflammation and oxidative stress via keap1/nrf2/nf-κb signaling pathways
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10596063/
https://www.ncbi.nlm.nih.gov/pubmed/37881650
http://dx.doi.org/10.2147/JIR.S430423
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