Cargando…

Gallic Acid Alleviates Neuropathic Pain Behaviors in Rats by Inhibiting P2X7 Receptor-Mediated NF-κB/STAT3 Signaling Pathway

Neuropathic pain is a complex disease with high incidence. Adenosine triphosphate (ATP) and its activated P2X7 receptor are involved in the signal transmission of neuropathic pain. Gallic acid (3,4,5-trihydroxybenzoic acid) is a traditional Chinese medicine obtained from natural plants that exhibit...

Descripción completa

Detalles Bibliográficos
Autores principales: Yang, Runan, Li, Zijing, Zou, Yuting, Yang, Jingjian, Li, Lin, Xu, Xiumei, Schmalzing, Günther, Nie, Hong, Li, Guilin, Liu, Shuangmei, Liang, Shangdong, Xu, Changshui
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423904/
https://www.ncbi.nlm.nih.gov/pubmed/34512324
http://dx.doi.org/10.3389/fphar.2021.680139
_version_ 1783749559855349760
author Yang, Runan
Li, Zijing
Zou, Yuting
Yang, Jingjian
Li, Lin
Xu, Xiumei
Schmalzing, Günther
Nie, Hong
Li, Guilin
Liu, Shuangmei
Liang, Shangdong
Xu, Changshui
author_facet Yang, Runan
Li, Zijing
Zou, Yuting
Yang, Jingjian
Li, Lin
Xu, Xiumei
Schmalzing, Günther
Nie, Hong
Li, Guilin
Liu, Shuangmei
Liang, Shangdong
Xu, Changshui
author_sort Yang, Runan
collection PubMed
description Neuropathic pain is a complex disease with high incidence. Adenosine triphosphate (ATP) and its activated P2X7 receptor are involved in the signal transmission of neuropathic pain. Gallic acid (3,4,5-trihydroxybenzoic acid) is a traditional Chinese medicine obtained from natural plants that exhibit anti-inflammatory, analgesic, and antitumor effects. However, the underlying mechanism for gallic acid in analgesia remains unknown. This study aims to reveal how gallic acid alleviates neuropathic pain behaviors in a rat model with chronic constriction injury (CCI). Real-time PCR, western blotting, double-label immunofluorescence, molecular docking, and whole-cell patch clamp technology were used to explore the therapeutic action of gallic acid on neuropathic pain. The results showed that after CCI rats were treated with gallic acid for 1 week, the mechanical withdrawal threshold and thermal withdrawal latency were increased, accompanied by inhibition of the upregulated expression of P2X7 and TNF-α at both mRNA and protein levels, and reduced NF-κB and phosphorylated-STAT3 in the dorsal root ganglia. At the same time, gallic acid significantly decreased the coexpression of P2X7 and glial fibrillary acidic protein in the dorsal root ganglia. In addition, gallic acid could suppress ATP-activated current in human embryonic kidney 293 (HEK293) cells transfected with the plasmid expressing P2X7 but had no effect on ATP activation current of P2X7-mutant plasmid (with the point mutation sequence of the key site where gallic acid binds to the P2X7 receptor). Therefore, our work suggests that gallic acid may alleviate neuropathic pain in CCI rats by inhibiting the P2X7 receptor and subsequent activation of the TNF-α/STAT3 signaling pathway.
format Online
Article
Text
id pubmed-8423904
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-84239042021-09-09 Gallic Acid Alleviates Neuropathic Pain Behaviors in Rats by Inhibiting P2X7 Receptor-Mediated NF-κB/STAT3 Signaling Pathway Yang, Runan Li, Zijing Zou, Yuting Yang, Jingjian Li, Lin Xu, Xiumei Schmalzing, Günther Nie, Hong Li, Guilin Liu, Shuangmei Liang, Shangdong Xu, Changshui Front Pharmacol Pharmacology Neuropathic pain is a complex disease with high incidence. Adenosine triphosphate (ATP) and its activated P2X7 receptor are involved in the signal transmission of neuropathic pain. Gallic acid (3,4,5-trihydroxybenzoic acid) is a traditional Chinese medicine obtained from natural plants that exhibit anti-inflammatory, analgesic, and antitumor effects. However, the underlying mechanism for gallic acid in analgesia remains unknown. This study aims to reveal how gallic acid alleviates neuropathic pain behaviors in a rat model with chronic constriction injury (CCI). Real-time PCR, western blotting, double-label immunofluorescence, molecular docking, and whole-cell patch clamp technology were used to explore the therapeutic action of gallic acid on neuropathic pain. The results showed that after CCI rats were treated with gallic acid for 1 week, the mechanical withdrawal threshold and thermal withdrawal latency were increased, accompanied by inhibition of the upregulated expression of P2X7 and TNF-α at both mRNA and protein levels, and reduced NF-κB and phosphorylated-STAT3 in the dorsal root ganglia. At the same time, gallic acid significantly decreased the coexpression of P2X7 and glial fibrillary acidic protein in the dorsal root ganglia. In addition, gallic acid could suppress ATP-activated current in human embryonic kidney 293 (HEK293) cells transfected with the plasmid expressing P2X7 but had no effect on ATP activation current of P2X7-mutant plasmid (with the point mutation sequence of the key site where gallic acid binds to the P2X7 receptor). Therefore, our work suggests that gallic acid may alleviate neuropathic pain in CCI rats by inhibiting the P2X7 receptor and subsequent activation of the TNF-α/STAT3 signaling pathway. Frontiers Media S.A. 2021-08-25 /pmc/articles/PMC8423904/ /pubmed/34512324 http://dx.doi.org/10.3389/fphar.2021.680139 Text en Copyright © 2021 Yang, Li, Zou, Yang, Li, Xu, Schmalzing, Nie, Li, Liu, Liang and Xu. 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, Runan
Li, Zijing
Zou, Yuting
Yang, Jingjian
Li, Lin
Xu, Xiumei
Schmalzing, Günther
Nie, Hong
Li, Guilin
Liu, Shuangmei
Liang, Shangdong
Xu, Changshui
Gallic Acid Alleviates Neuropathic Pain Behaviors in Rats by Inhibiting P2X7 Receptor-Mediated NF-κB/STAT3 Signaling Pathway
title Gallic Acid Alleviates Neuropathic Pain Behaviors in Rats by Inhibiting P2X7 Receptor-Mediated NF-κB/STAT3 Signaling Pathway
title_full Gallic Acid Alleviates Neuropathic Pain Behaviors in Rats by Inhibiting P2X7 Receptor-Mediated NF-κB/STAT3 Signaling Pathway
title_fullStr Gallic Acid Alleviates Neuropathic Pain Behaviors in Rats by Inhibiting P2X7 Receptor-Mediated NF-κB/STAT3 Signaling Pathway
title_full_unstemmed Gallic Acid Alleviates Neuropathic Pain Behaviors in Rats by Inhibiting P2X7 Receptor-Mediated NF-κB/STAT3 Signaling Pathway
title_short Gallic Acid Alleviates Neuropathic Pain Behaviors in Rats by Inhibiting P2X7 Receptor-Mediated NF-κB/STAT3 Signaling Pathway
title_sort gallic acid alleviates neuropathic pain behaviors in rats by inhibiting p2x7 receptor-mediated nf-κb/stat3 signaling pathway
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8423904/
https://www.ncbi.nlm.nih.gov/pubmed/34512324
http://dx.doi.org/10.3389/fphar.2021.680139
work_keys_str_mv AT yangrunan gallicacidalleviatesneuropathicpainbehaviorsinratsbyinhibitingp2x7receptormediatednfkbstat3signalingpathway
AT lizijing gallicacidalleviatesneuropathicpainbehaviorsinratsbyinhibitingp2x7receptormediatednfkbstat3signalingpathway
AT zouyuting gallicacidalleviatesneuropathicpainbehaviorsinratsbyinhibitingp2x7receptormediatednfkbstat3signalingpathway
AT yangjingjian gallicacidalleviatesneuropathicpainbehaviorsinratsbyinhibitingp2x7receptormediatednfkbstat3signalingpathway
AT lilin gallicacidalleviatesneuropathicpainbehaviorsinratsbyinhibitingp2x7receptormediatednfkbstat3signalingpathway
AT xuxiumei gallicacidalleviatesneuropathicpainbehaviorsinratsbyinhibitingp2x7receptormediatednfkbstat3signalingpathway
AT schmalzinggunther gallicacidalleviatesneuropathicpainbehaviorsinratsbyinhibitingp2x7receptormediatednfkbstat3signalingpathway
AT niehong gallicacidalleviatesneuropathicpainbehaviorsinratsbyinhibitingp2x7receptormediatednfkbstat3signalingpathway
AT liguilin gallicacidalleviatesneuropathicpainbehaviorsinratsbyinhibitingp2x7receptormediatednfkbstat3signalingpathway
AT liushuangmei gallicacidalleviatesneuropathicpainbehaviorsinratsbyinhibitingp2x7receptormediatednfkbstat3signalingpathway
AT liangshangdong gallicacidalleviatesneuropathicpainbehaviorsinratsbyinhibitingp2x7receptormediatednfkbstat3signalingpathway
AT xuchangshui gallicacidalleviatesneuropathicpainbehaviorsinratsbyinhibitingp2x7receptormediatednfkbstat3signalingpathway