Mechanism of Paeonol in Alleviating Alcohol-induced Liver Injury in Mice Through Regulating SCFAs-GPR43/MAPK Signaling Pathway Mediated by Intestinal Flora
10.13422/j.cnki.syfjx.20250406
- VernacularTitle:丹皮酚通过调节肠道菌群介导的SCFAs-GPR43/MAPK信号通路减轻小鼠酒精性肝损伤的作用机制
- Author:
Shengnan JIANG
1
;
Qifeng WU
2
;
Zining WANG
1
;
Hao PU
1
;
Guiming YAN
2
Author Information
1. College of Pharmacy，Anhui University of Chinese Medicine，Hefei 230012，China
2. School of Integrated Chinese and Western Medicine，Anhui University of Chinese Medicine， Hefei 230012，China
- Publication Type:Journal Article
- Keywords:
paeonol;
acute alcohol-induced liver injury;
intestinal flora;
intestinal barrier;
short-chain fatty acids-specific receptor （GPR43）/mitogen-activated protein kinase （MAPK） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(12):129-139
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the ameliorative effect of paeonol on acute alcohol-induced hepatic inflammation in mice via the regulation of the short-chain fatty acids （SCFAs）-specific receptor GPR43/mitogen-activated protein kinase （MAPK） signaling pathway. MethodsC57BL/6 mice were randomly divided into five groups： blank control group， model group， low-dose paeonol group （120 mg·kg-1）， high-dose paeonol group （480 mg·kg-1）， and silybin group （36.8 mg·kg-1）. A mouse model of alcohol-induced liver disease （ALD） was established by ad libitum administration of a Lieber-DeCarli alcohol liquid diet. Serum lipid levels， liver function， inflammatory cytokines， and oxidative stress markers were measured. Liver hematoxylin-eosin （HE） staining and Oil Red O staining were performed to validate successful modeling. Western blot analysis was used to assess the expression levels of zonula occludens-1 （ZO-1）， Claudin-1， and proteins related to the GPR43/MAPK signaling pathway in the colonic tissue. Immunohistochemistry was employed to detect the protein expression of GPR43， ZO-1， and Claudin-1 in the colon. Then 16S rDNA sequencing was performed to analyze differences in intestinal flora between the model group and the high-dose paeonol group. Additionally， fecal microbiota transplantation （FMT） experiments were conducted to validate the regulatory effect of paeonol on ALD via modulation of intestinal flora. ResultsCompared with the blank control group， the model group showed significantly elevated serum lipid levels， oxidative stress， and inflammatory cytokine expression （P<0.01）. Liver histology revealed increased inflammatory infiltration and lipid droplet accumulation. Colonic mucosal injury and impaired intestinal barrier function were observed. Levels of MAPK pathway-related proteins in the colonic tissue were upregulated （P<0.01）， while GPR43， ZO-1， and Claudin-1 protein expression levels were significantly decreased （P<0.01）. The composition and abundance of the intestinal flora were markedly altered， with a reduced Bacteroidetes-to-Firmicutes ratio and decreased relative abundances of Eubacterium， Parabacteroides， Erysipelothrix， and Adlercreutzia， alongside increased abundances of Clostridium butyricum， Enterococcus， and Helicobacter pylori in the model group. Compared with the model group， paeonol significantly reduced serum lipid levels， oxidative stress responses， and the expression of inflammatory cytokines in ALD mice （P<0.05， P<0.01）. It also attenuated hepatic lipid accumulation， restored intestinal barrier function， and repaired the structural integrity of liver and colonic tissues. The protein expression levels of ZO-1， Claudin-1， and GPR43 in the colonic tissue were significantly increased （P<0.05， P<0.01）， while those of MAPK pathway-related proteins were significantly decreased （P<0.05， P<0.01）. The intestinal flora dysbiosis was effectively alleviated， rendering its composition closer to that of normal mice. The efficacy of paeonol in modulating ALD was further confirmed by FMT experiments， supporting its mechanistic involvement in the SCFAs-GPR43/MAPK signaling pathway. ConclusionPaeonol exerts a protective effect against ALD in mice， which may be mediated through regulation of the SCFAs-GPR43/MAPK signaling pathway， thereby achieving anti-inflammatory effects and improving intestinal barrier function.
