ScRNA‐Seq Reveals Jiangfu Zhixie Formula Alleviates IBS‐D by Inhibiting Macrophage M1 Polarization through HIF‐1α‐Glycolysis Axis
- 1Research Center, Hebei Provincial Hospital of Chinese Medicine Hebei China
- 2Department of Spleen and Stomach Diseases Hebei Provincial Hospital of Chinese Medicine Hebei China
Abstract
Background: Irritable bowel syndrome with diarrhea (IBS‐D) remains a challenging condition to manage due to its chronic nature and the limited long‐term efficacy of current treatments. The traditional Chinese herbal formula Jiangfu Zhixie (JFZX) has shown clinical benefits, but its underlying mechanisms remain unclear.
Aim: This study aimed to investigate the therapeutic effects of JFZX on IBS‐D and elucidate its molecular mechanisms, focusing on macrophage polarization and the HIF‐1α‐glycolysis axis.
Methods: An IBS‐D mouse model was established by senna leaf infusion combined with restraint stress. Mice were treated with varying doses of JFZX or pinaverium bromide (positive control) for 14 days. Diarrhea symptoms, visceral hypersensitivity, and intestinal barrier integrity were assessed. Single‐cell RNA sequencing (scRNA‐seq) was performed on colon tissues to analyze cellular composition and intercellular interactions. In vitro, LPS‐stimulated RAW264.7 macrophages were treated with JFZX‐medicated serum to evaluate M1 polarization, cytokine secretion (IL‐1β, TNF‐α), and expression of HIF‐1α and glycolysis‐related proteins (GLUT1, LDHA).
Results: JFZX treatment significantly ameliorated diarrhea, reduced visceral hypersensitivity, and restored intestinal barrier integrity in IBS‐D mice, accompanied by upregulation of tight junction proteins ZO‐1 and Occludin. scRNA‐seq revealed that JFZX reshaped the colonic cellular landscape, attenuating myeloid‐epithelial interactions and reducing the proportion of pro‐inflammatory M1‐like macrophages. Mechanistically, HIF‐1α was identified as a key driver of M1 polarization in IBS‐D. JFZX suppressed HIF‐1α expression and its downstream glycolytic pathway (GLUT1, LDHA) both in vivo and in vitro, thereby inhibiting M1 macrophage polarization and decreasing IL‐1β and TNF‐α secretion in LPS‐stimulated macrophages.
Conclusion: JFZX alleviates IBS‐D by inhibiting M1 macrophage polarization through suppression of the HIF‐1α‐glycolysis axis, highlighting its potential as a therapeutic agent for IBS‐D and identifying HIF‐1α as a promising target for intervention.
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BibTeX
@article{xu2026scrnaseq,
title = {{ScRNA‐Seq Reveals Jiangfu Zhixie Formula Alleviates IBS‐D by Inhibiting Macrophage M1 Polarization through HIF‐1α‐Glycolysis Axis}},
author = {Xiaosong Xu and Yao Du and Lipeng Du and Wanning Zhang and Bowen Guo and Yanru Cai and Tianyi Zhang},
journal = {Immunity, Inflammation and Disease},
year = {2026},
month = nov,
doi = {10.1002/iid3.70599},
url = {https://doi.org/10.1002/iid3.70599},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - ScRNA‐Seq Reveals Jiangfu Zhixie Formula Alleviates IBS‐D by Inhibiting Macrophage M1 Polarization through HIF‐1α‐Glycolysis Axis
AU - Xiaosong Xu
AU - Yao Du
AU - Lipeng Du
AU - Wanning Zhang
AU - Bowen Guo
AU - Yanru Cai
AU - Tianyi Zhang
PY - 2026
DA - 2026/11/05
JO - Immunity, Inflammation and Disease
DO - 10.1002/iid3.70599
UR - https://doi.org/10.1002/iid3.70599
AB - Background: Irritable bowel syndrome with diarrhea (IBS‐D) remains a challenging condition to manage due to its chronic nature and the limited long‐term efficacy of current treatments. The traditional Chinese herbal formula Jiangfu Zhixie (JFZX) has shown clinical benefits, but its underlying mechanisms remain unclear. Aim: This study aimed to investigate the therapeutic effects of JFZX on IBS‐D and elucidate its molecular mechanisms, focusing on macrophage polarization and the HIF‐1α‐glycolysis axis. Methods: An IBS‐D mouse model was established by senna leaf infusion combined with restraint stress. Mice were treated with varying doses of JFZX or pinaverium bromide (positive control) for 14 days. Diarrhea symptoms, visceral hypersensitivity, and intestinal barrier integrity were assessed. Single‐cell RNA sequencing (scRNA‐seq) was performed on colon tissues to analyze cellular composition and intercellular interactions. In vitro, LPS‐stimulated RAW264.7 macrophages were treated with JFZX‐medicated serum to evaluate M1 polarization, cytokine secretion (IL‐1β, TNF‐α), and expression of HIF‐1α and glycolysis‐related proteins (GLUT1, LDHA). Results: JFZX treatment significantly ameliorated diarrhea, reduced visceral hypersensitivity, and restored intestinal barrier integrity in IBS‐D mice, accompanied by upregulation of tight junction proteins ZO‐1 and Occludin. scRNA‐seq revealed that JFZX reshaped the colonic cellular landscape, attenuating myeloid‐epithelial interactions and reducing the proportion of pro‐inflammatory M1‐like macrophages. Mechanistically, HIF‐1α was identified as a key driver of M1 polarization in IBS‐D. JFZX suppressed HIF‐1α expression and its downstream glycolytic pathway (GLUT1, LDHA) both in vivo and in vitro, thereby inhibiting M1 macrophage polarization and decreasing IL‐1β and TNF‐α secretion in LPS‐stimulated macrophages. Conclusion: JFZX alleviates IBS‐D by inhibiting M1 macrophage polarization through suppression of the HIF‐1α‐glycolysis axis, highlighting its potential as a therapeutic agent for IBS‐D and identifying HIF‐1α as a promising target for intervention.
SN - 2050-4527
ER -