Effect and Mechanisms of Shaoyaotang on Murine Ulcerative Colitis via Modulating Macrophage Glycolytic Reprogramming and Polarization Through HIF-1α Pathway
10.13422/j.cnki.syfjx.20260541
- VernacularTitle:芍药汤通过HIF-1α通路干预巨噬细胞糖代谢重编程及极化治疗小鼠溃疡性结肠炎的作用与机制
- Author:
Yiqian YU
1
;
Hui CAO
1
;
Dongsheng WU
1
;
Bo ZOU
1
;
Ruoru HUANG
1
;
Qi CHENG
1
;
Youwei XIAO
1
;
Yan GONG
1
;
Jiachun XIONG
1
Author Information
1. The First Hospital of Hunan University of Chinese Medicine，Changsha 410007，China
- Publication Type:Journal Article
- Keywords:
ulcerative colitis;
Shaoyaotang;
glycolytic reprogramming;
macrophages
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(13):53-60
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the potential role and underlying mechanisms of Shaoyaotang in intervening macrophage glycolytic reprogramming in ulcerative colitis （UC）. MethodsForty-eight C57BL/6 mice were randomly divided into six groups： Normal control group， model group， mesalazine group （0.39 g·kg-1）， Shaoyaotang group （15.54 g·kg-1）， 2-deoxy-D-glucose （2-DG） group （glycolysis inhibitor， 100 mg·kg-1）， and 2-DG + Shaoyaotang combined group （100 mg·kg-1+15.54 g·kg-1）. Except for the normal control group， mice in the other five groups were induced to establish UC models using dextran sulfate sodium （DSS）. The normal control group was administered pure water via intragastric gavage， while the other groups received intragastric gavage of mesalazine solution， intragastric gavage of Shaoyaotang， and the 2-DG group was treated with 2-DG via intraperitoneal injection. After 7 consecutive days of treatment， colonic tissues were extracted. Hematoxylin and eosin （HE） staining was performed to evaluate histopathological changes and tissue injury in the colon. Enzyme-linked immunosorbent assay （ELISA） was used to detect the expression of interleukin-10 （IL-10） and tumor necrosis factor-α （TNF-α） in colonic tissues. Western blot analysis was employed to determine the expression levels of hypoxia-inducible factor-1α （HIF-1α）， glucose transporter （GLUT1）， lactate dehydrogenase A （LDHA）， pyruvate kinase M2 （PKM2）， and 6-phosphofructo-2-kinase/fructose-2，6-biphosphatase 3 （PFKFB3） in colonic tissues. Immunofluorescence was conducted to detect the expression of CD206 and inducible nitric oxide synthase （iNOS） in colonic tissues. Liquid chromatography-mass spectrometry （LC-MS） was utilized to measure lactate and citrate levels in colonic tissues. ResultsCompared with the normal control group， mice in the model group exhibited a significant increase in disease activity index （DAI） scores， accompanied by colonic mucosal congestion， edema， and inflammatory cell infiltration， significantly elevated expression of the inflammatory cytokine TNF-α （P<0.05）， significantly decreased IL-10 expression （P<0.05）， significantly increased levels of HIF-1α， GLUT1， LDHA， PKM2， and PFKFB3 in colonic tissues （P<0.05）， markedly elevated iNOS expression （P<0.05）， significantly decreased CD206 expression （P<0.05）， and significantly elevated lactate and citrate levels in colonic tissues （P<0.05）. In contrast to the model group， the Shaoyaotang group， inhibitor group， and Shaoyaotang combined with inhibitor group demonstrated amelioration of mucosal injury in colonic tissues， markely decreased expression levels of the inflammatory cytokine TNF-α （P<0.05）， elevated IL-10 expression levels， significantly decreased expression of HIF-1α， GLUT1， LDHA， PKM2， and PFKFB3 （P<0.05）， markedly reduced iNOS expression levels （P<0.05）， significantly increased CD206 expression （P<0.05） and significantly decreased lactate and citrate levels （P<0.05）. ConclusionShaoyaotang ameliorates symptoms of DSS-induced UC in mice， and its therapeutic mechanism may be associated with regulating macrophage glycolytic reprogramming via modulation of the HIF-1α signaling pathway.
