Gallic Acid Alleviates Paclitaxel-Induced Neuroinflammation through Regulation of the NLRP3 Inflammasome Pathway
10.14148/j.issn.1672-0482.2024.1178
- VernacularTitle:没食子酸通过调控NLRP3炎症体通路缓解紫杉醇所致神经炎症的研究
- Author:
Yang CHEN
1
;
Jiayi CHEN
;
Jing ZHU
Author Information
1. 南京中医药大学药学院,江苏 南京 210023
- Keywords:
paclitaxel;
gallic acid;
NLRP3 inflammasome;
peripheral nerve injury;
neuroinflammation
- From:
Journal of Nanjing University of Traditional Chinese Medicine
2024;40(11):1178-1188
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the protective effect and mechanism of gallic acid(GA)on paclitaxel-induced peripheral neuropathy.METHODS The primary dorsal root ganglion(DRG)was extracted to establish an in vitro model of paclitaxel-induced DRG cell injury;CCK-8 assay was used to evaluate the neuroprotective effects of GA on this model.The paclitaxel-induced neuro-pathic pain model in C57BL/6J mice was established,and the behavioral test was used to analyze effects of GA alleviating paclitaxel-induced peripheral neuropathy and to explore whether GA alleviated paclitaxel-induced peripheral neuropathic pain by inhibiting the activation of NLRP3 inflammatory and reducing the release of pro-inflammatory cytokine.qPCR was used to detect the expression lev-els of NLRP3,Caspase-1,and IL-1β mRNA in DRG cells;Western blot was used to detect the change of protein levels of NLRP3,Caspase-1,and IL-1β;and the fluorescence intensity of NLRP3,Caspase-1,and IL-1β proteins was analyzed by immunofluores-cence staining.RESULTS GA exerts a protective effect and improved the survival rate of paclitaxel-stimulated DRG cells;reduced mechanical,cold and thermal pain hyperalgesia in mice;effectively reversed the elevated expression levels of NLRP3 and Caspase-1 in paclitaxel-stimulated DRG cells and reduced the release of pro-inflammatory cytokine IL-1β,which ameliorated the neuroinflam-matory response induced by paclitaxel.CONCLUSION Gallic acid improves paclitaxel-induced neuroinflammation by regulating the NLRP3 inflammasome pathway.The NLRP3/Caspase-1/IL-1β pathway is one of the potential mechanisms for the treatment of pacli-taxel-induced peripheral neuropathy.