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Higenamine Attenuates Neuropathic Pain by Inhibition of NOX2/ROS/TRP/P38 Mitogen-Activated Protein Kinase/NF-ĸB Signaling Pathway

Oxidative stress damage is known as one of the important factors that induce neuropathic pain (NP). Using antioxidant therapy usually achieves an obvious curative effect and alleviates NP. Previous pharmacological studies have shown that higenamine (Hig) performs to be antioxidant and anti-inflammat...

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Autores principales: Yang, Bing, Ma, Shengsuo, Zhang, Chunlan, Sun, Jianxin, Zhang, Di, Chang, Shiquan, Lin, Yi, Zhao, Guoping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497786/
https://www.ncbi.nlm.nih.gov/pubmed/34630095
http://dx.doi.org/10.3389/fphar.2021.716684
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author Yang, Bing
Ma, Shengsuo
Zhang, Chunlan
Sun, Jianxin
Zhang, Di
Chang, Shiquan
Lin, Yi
Zhao, Guoping
author_facet Yang, Bing
Ma, Shengsuo
Zhang, Chunlan
Sun, Jianxin
Zhang, Di
Chang, Shiquan
Lin, Yi
Zhao, Guoping
author_sort Yang, Bing
collection PubMed
description Oxidative stress damage is known as one of the important factors that induce neuropathic pain (NP). Using antioxidant therapy usually achieves an obvious curative effect and alleviates NP. Previous pharmacological studies have shown that higenamine (Hig) performs to be antioxidant and anti-inflammatory. However, the protective effect and mechanism of Hig on NP are still unclear. This study mainly evaluated the changes in reactive oxygen species (ROS) level, lipid peroxidation, and antioxidant system composed of superoxide dismutase (SOD) and glutathione (GSH) through chronic constrict injury (CCI) model rats and t-BHP-induced Schwann cell (SC) oxidative stress model. The expressions of two inflammatory factors, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were also assessed. The possible molecular mechanism of Hig in the treatment of NP was explored in conjunction with the expression of mitochondrial apoptosis pathway and NOX2/ROS/TRP/P38 mitogen-activated protein kinase (MAPK)/NF-ĸB pathway-related indicators. Hig showed substantial antioxidant and anti-inflammatory properties both in vivo and in vitro. Hig significantly reduced the upregulated levels of ROS, malondialdehyde (MDA), TNF-α, and IL-6 and increased the levels of SOD and GSH, which rebalanced the redox system and improved the survival rate of cells. In the animal behavioral test, it was also observed that Hig relieved the CCI-induced pain, indicating that Hig had a pain relief effect. Our research results suggested that Hig improved NP-induced oxidative stress injury, inflammation, and apoptosis, and this neuroprotective effect may be related to the NOX2/ROS/TRP/P38 MAPK/NF-ĸB signaling pathway.
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spelling pubmed-84977862021-10-09 Higenamine Attenuates Neuropathic Pain by Inhibition of NOX2/ROS/TRP/P38 Mitogen-Activated Protein Kinase/NF-ĸB Signaling Pathway Yang, Bing Ma, Shengsuo Zhang, Chunlan Sun, Jianxin Zhang, Di Chang, Shiquan Lin, Yi Zhao, Guoping Front Pharmacol Pharmacology Oxidative stress damage is known as one of the important factors that induce neuropathic pain (NP). Using antioxidant therapy usually achieves an obvious curative effect and alleviates NP. Previous pharmacological studies have shown that higenamine (Hig) performs to be antioxidant and anti-inflammatory. However, the protective effect and mechanism of Hig on NP are still unclear. This study mainly evaluated the changes in reactive oxygen species (ROS) level, lipid peroxidation, and antioxidant system composed of superoxide dismutase (SOD) and glutathione (GSH) through chronic constrict injury (CCI) model rats and t-BHP-induced Schwann cell (SC) oxidative stress model. The expressions of two inflammatory factors, tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), were also assessed. The possible molecular mechanism of Hig in the treatment of NP was explored in conjunction with the expression of mitochondrial apoptosis pathway and NOX2/ROS/TRP/P38 mitogen-activated protein kinase (MAPK)/NF-ĸB pathway-related indicators. Hig showed substantial antioxidant and anti-inflammatory properties both in vivo and in vitro. Hig significantly reduced the upregulated levels of ROS, malondialdehyde (MDA), TNF-α, and IL-6 and increased the levels of SOD and GSH, which rebalanced the redox system and improved the survival rate of cells. In the animal behavioral test, it was also observed that Hig relieved the CCI-induced pain, indicating that Hig had a pain relief effect. Our research results suggested that Hig improved NP-induced oxidative stress injury, inflammation, and apoptosis, and this neuroprotective effect may be related to the NOX2/ROS/TRP/P38 MAPK/NF-ĸB signaling pathway. Frontiers Media S.A. 2021-09-24 /pmc/articles/PMC8497786/ /pubmed/34630095 http://dx.doi.org/10.3389/fphar.2021.716684 Text en Copyright © 2021 Yang, Ma, Zhang, Sun, Zhang, Chang, Lin and Zhao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Yang, Bing
Ma, Shengsuo
Zhang, Chunlan
Sun, Jianxin
Zhang, Di
Chang, Shiquan
Lin, Yi
Zhao, Guoping
Higenamine Attenuates Neuropathic Pain by Inhibition of NOX2/ROS/TRP/P38 Mitogen-Activated Protein Kinase/NF-ĸB Signaling Pathway
title Higenamine Attenuates Neuropathic Pain by Inhibition of NOX2/ROS/TRP/P38 Mitogen-Activated Protein Kinase/NF-ĸB Signaling Pathway
title_full Higenamine Attenuates Neuropathic Pain by Inhibition of NOX2/ROS/TRP/P38 Mitogen-Activated Protein Kinase/NF-ĸB Signaling Pathway
title_fullStr Higenamine Attenuates Neuropathic Pain by Inhibition of NOX2/ROS/TRP/P38 Mitogen-Activated Protein Kinase/NF-ĸB Signaling Pathway
title_full_unstemmed Higenamine Attenuates Neuropathic Pain by Inhibition of NOX2/ROS/TRP/P38 Mitogen-Activated Protein Kinase/NF-ĸB Signaling Pathway
title_short Higenamine Attenuates Neuropathic Pain by Inhibition of NOX2/ROS/TRP/P38 Mitogen-Activated Protein Kinase/NF-ĸB Signaling Pathway
title_sort higenamine attenuates neuropathic pain by inhibition of nox2/ros/trp/p38 mitogen-activated protein kinase/nf-ĸb signaling pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497786/
https://www.ncbi.nlm.nih.gov/pubmed/34630095
http://dx.doi.org/10.3389/fphar.2021.716684
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