Ginseng-derived extracellular vesicles alleviate ulcerative colitis by regulating macrophage glycolytic reprogramming and H3K18la-mediated epigenetic modification
6 affiliations
- 1The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, China; Key Laboratory of Gastrointestinal Cancer Etiology and Prevention, Shenyang, China
- 2Key Laboratory of Gastrointestinal Cancer Etiology and Prevention, Shenyang, China; Department of Anorectal Surgery, The First Hospital of China Medical University, Shenyang, China
- 3School of Clinical Medicine, Jiangxi University of Chinese Medicine, Nanchang, China
- 4Department of Laboratory Medicine, Shengjing Hospital of China Medical University, No. 36, San Hao Street, Shenyang, China; Corresponding author.
- 5The First Laboratory of Cancer Institute, The First Hospital of China Medical University, Shenyang, China; Key Laboratory of Gastrointestinal Cancer Etiology and Prevention, Shenyang, China; Corresponding author. The First Laboratory of Cancer Institute, The First Hospital of China Medical University, NO.155, North Nanjing Street, Heping District, Shenyang City, 110001, China.
- 6Key Laboratory of Gastrointestinal Cancer Etiology and Prevention, Shenyang, China; Department of Anorectal Surgery, The First Hospital of China Medical University, Shenyang, China; Corresponding author. Department of Anorectal Surgery, The First Hospital of China Medical University, Shenyang, China.
Abstract
Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited treatment options due to adverse effects and variable response rates. Plant-derived extracellular vesicles have emerged as promising therapeutic agents owing to their biocompatibility. Although Panax ginseng exhibits anti-inflammatory properties, the role of ginseng-derived extracellular vesicles (GEs) in UC remains unclear. Methods: GEs were isolated and characterized. The therapeutic effects of GEs were evaluated in DSS-induced UC mice. Single-cell RNA sequencing was performed to profile colonic immune cells. In vitro experiments using RAW264.7 macrophages and Caco-2 intestinal epithelial cells were conducted to investigate macrophage polarization, glycolytic metabolism, histone lactylation, and barrier function. Gut microbiota and short-chain fatty acid (SCFA) profiles were analyzed by 16S rRNA sequencing and gas chromatography. Results: GEs alleviated DSS-induced colitis symptoms, reduced pro-inflammatory cytokines, restored tight junction proteins, and exhibited good biosafety. Single-cell sequencing revealed that GEs remodeled colonic macrophage subsets, reducing pro-inflammatory Ccl7 + macrophages while increasing Pmepa1 + and Vcam1 + populations, and suppressed glycolytic signatures. In vitro, GEs were internalized by macrophages, inhibited LPS-induced M1 polarization, downregulated GLUT1 and LDHA expression, and reduced ATP and lactate production. Mechanistically, GEs specifically decreased H3K18la enrichment at the IL6, TNFA, and INOS promoters, an effect reversed by exogenous lactate. Additionally, GEs restored gut dysbiosis and elevated levels of propionic, acetic, butyric, and isovaleric acids, which correlated with improved disease phenotypes. Conclusion: This study demonstrates that GEs alleviate UC by inhibiting macrophage glycolysis, reducing H3K18la-mediated pro-inflammatory gene expression, protecting the intestinal barrier, and modulating the gut microbiota. These results offer new experimental support for GE-based UC therapy and establish a basis for mechanistic and translational follow-up studies.
Related
- Hydatid Cyst Fluid of Echinococcus granulosus Alleviates Experimental Ulcerative Colitis by Suppressing Inflammation and Oxidative Stress and Regulating the Gut Microbiota
- Host Metabolic Reprogramming Defines Macrophage Antifungal Activity Against Cryptococcus neoformans
- Mesaconate-Based Polyester Nanoparticles Reveal How Metabolite Isomerism Shapes Polymer Behavior, Macrophage Reprogramming, and Systemic Immunomodulation
- Polarized macrophage-derived microvesicles differentially modulate intestinal barrier dysfunction and endoplasmic reticulum stress in ulcerative colitis.
- PPARγ brakes cytosolic DNA-induced macrophage inflammation by super-enhancer metabolic reprogramming
BibTeX
@article{zhang2026ginsengderived,
title = {{Ginseng-derived extracellular vesicles alleviate ulcerative colitis by regulating macrophage glycolytic reprogramming and H3K18la-mediated epigenetic modification}},
author = {Yuzhe Zhang and Ruipeng Li and Yuan Yang and Fang Li and Jianzhong Liang and Shupeng Chen and Lina Wu and Ye Zhang and Yanke Li},
journal = {Journal of Ginseng Research},
year = {2026},
month = aug,
doi = {10.1016/j.jgr.2026.101123},
url = {https://doi.org/10.1016/j.jgr.2026.101123},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Ginseng-derived extracellular vesicles alleviate ulcerative colitis by regulating macrophage glycolytic reprogramming and H3K18la-mediated epigenetic modification
AU - Yuzhe Zhang
AU - Ruipeng Li
AU - Yuan Yang
AU - Fang Li
AU - Jianzhong Liang
AU - Shupeng Chen
AU - Lina Wu
AU - Ye Zhang
AU - Yanke Li
PY - 2026
DA - 2026/08/06
JO - Journal of Ginseng Research
DO - 10.1016/j.jgr.2026.101123
UR - https://doi.org/10.1016/j.jgr.2026.101123
AB - Background: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with limited treatment options due to adverse effects and variable response rates. Plant-derived extracellular vesicles have emerged as promising therapeutic agents owing to their biocompatibility. Although Panax ginseng exhibits anti-inflammatory properties, the role of ginseng-derived extracellular vesicles (GEs) in UC remains unclear. Methods: GEs were isolated and characterized. The therapeutic effects of GEs were evaluated in DSS-induced UC mice. Single-cell RNA sequencing was performed to profile colonic immune cells. In vitro experiments using RAW264.7 macrophages and Caco-2 intestinal epithelial cells were conducted to investigate macrophage polarization, glycolytic metabolism, histone lactylation, and barrier function. Gut microbiota and short-chain fatty acid (SCFA) profiles were analyzed by 16S rRNA sequencing and gas chromatography. Results: GEs alleviated DSS-induced colitis symptoms, reduced pro-inflammatory cytokines, restored tight junction proteins, and exhibited good biosafety. Single-cell sequencing revealed that GEs remodeled colonic macrophage subsets, reducing pro-inflammatory Ccl7 + macrophages while increasing Pmepa1 + and Vcam1 + populations, and suppressed glycolytic signatures. In vitro, GEs were internalized by macrophages, inhibited LPS-induced M1 polarization, downregulated GLUT1 and LDHA expression, and reduced ATP and lactate production. Mechanistically, GEs specifically decreased H3K18la enrichment at the IL6, TNFA, and INOS promoters, an effect reversed by exogenous lactate. Additionally, GEs restored gut dysbiosis and elevated levels of propionic, acetic, butyric, and isovaleric acids, which correlated with improved disease phenotypes. Conclusion: This study demonstrates that GEs alleviate UC by inhibiting macrophage glycolysis, reducing H3K18la-mediated pro-inflammatory gene expression, protecting the intestinal barrier, and modulating the gut microbiota. These results offer new experimental support for GE-based UC therapy and establish a basis for mechanistic and translational follow-up studies.
SN - 1226-8453
SN - 2093-4947
ER -