Molecular mechanisms of plant-derived saponins against ulcerative colitis: a narrative review
- 1Department of Basic Medicine, Heilongjiang University of Traditional Chinese Medicine
- 2Department of Neurology, The Third Affiliated Hospital of Heilongjiang University of Chinese Medicine
- 3Department of Internal Medicine, The First Affiliated Hospital of Heilongjiang University of Chinese Medicine
Abstract
Ulcerative colitis (UC) is a chronic, relapsing-remitting inflammatory disorder of the colorectal mucosa whose incidence is rising globally. Current therapies remain limited by incomplete efficacy and long-term safety concerns, underscoring the need for novel, multi-targeted therapeutic agents. Plant-derived saponins, a structurally diverse class of triterpenoid and steroidal glycosides widely distributed in botanical drugs, have emerged as promising candidates owing to their capacity to simultaneously modulate multiple pathogenic axes of UC. This structured narrative review provides an evidence-graded account of the physiological and pathological mechanisms of UC, the chemical characteristics and pharmacological basis of plant-derived saponins, and the molecular mechanisms through which saponins counteract experimental colitis. Five interconnected mechanistic axes are delineated: suppression of pro-inflammatory signaling cascades, particularly NF-kB/MAPK and NLRP3 inflammasome pathways; protection and renewal of the intestinal epithelial barrier through tight junction restoration and mucin regulation; remodeling of the gut microbiota and its metabolite output, including short-chain fatty acid production; regulation of intestinal immune homeostasis via macrophage polarization and Th17/Treg balance; and control of oxidative stress, ferroptosis, and immunometabolic reprogramming. Mechanistic claims are graded by evidence level-distinguishing direct target engagement, inhibitor/genetic validation, and correlative downstream readouts-and parent saponins are distinguished from their microbiota-derived deglycosylation metabolites. This review further discusses the structural determinants of saponin bioactivity, gut-microbiota-dependent biotransformation, and current limitations including poor oral bioavailability, hemolytic potential, scarcity of clinical trials, and inter-individual microbiome variability. Future directions encompass structure-activity-guided scaffold optimization, advanced colon-targeted delivery systems, microbiome-stratified biomarker development, and systems-level target integration. Collectively, convergent preclinical evidence identifies plant-derived saponins as selectively multi-targeted candidates for UC; however, no purified plant-derived saponin has yet been tested in a randomised controlled trial in UC, and therapeutic claims must await evaluation against STRIDE-II targets such as faecal calprotectin normalisation, endoscopic healing and histological remission.
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BibTeX
@article{qu2026molecular,
title = {{Molecular mechanisms of plant-derived saponins against ulcerative colitis: a narrative review}},
author = {Chuncheng Qu and Bo Wang and Hang Su and Jiaqi Zhao and Rui Niu and Jian Zhang},
journal = {Frontiers in Pharmacology},
year = {2026},
month = nov,
doi = {10.3389/fphar.2026.1978896},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2026.1978896/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Molecular mechanisms of plant-derived saponins against ulcerative colitis: a narrative review
AU - Chuncheng Qu
AU - Bo Wang
AU - Hang Su
AU - Jiaqi Zhao
AU - Rui Niu
AU - Jian Zhang
PY - 2026
DA - 2026/11/03
JO - Frontiers in Pharmacology
DO - 10.3389/fphar.2026.1978896
UR - https://www.frontiersin.org/articles/10.3389/fphar.2026.1978896/full
AB - Ulcerative colitis (UC) is a chronic, relapsing-remitting inflammatory disorder of the colorectal mucosa whose incidence is rising globally. Current therapies remain limited by incomplete efficacy and long-term safety concerns, underscoring the need for novel, multi-targeted therapeutic agents. Plant-derived saponins, a structurally diverse class of triterpenoid and steroidal glycosides widely distributed in botanical drugs, have emerged as promising candidates owing to their capacity to simultaneously modulate multiple pathogenic axes of UC. This structured narrative review provides an evidence-graded account of the physiological and pathological mechanisms of UC, the chemical characteristics and pharmacological basis of plant-derived saponins, and the molecular mechanisms through which saponins counteract experimental colitis. Five interconnected mechanistic axes are delineated: suppression of pro-inflammatory signaling cascades, particularly NF-kB/MAPK and NLRP3 inflammasome pathways; protection and renewal of the intestinal epithelial barrier through tight junction restoration and mucin regulation; remodeling of the gut microbiota and its metabolite output, including short-chain fatty acid production; regulation of intestinal immune homeostasis via macrophage polarization and Th17/Treg balance; and control of oxidative stress, ferroptosis, and immunometabolic reprogramming. Mechanistic claims are graded by evidence level-distinguishing direct target engagement, inhibitor/genetic validation, and correlative downstream readouts-and parent saponins are distinguished from their microbiota-derived deglycosylation metabolites. This review further discusses the structural determinants of saponin bioactivity, gut-microbiota-dependent biotransformation, and current limitations including poor oral bioavailability, hemolytic potential, scarcity of clinical trials, and inter-individual microbiome variability. Future directions encompass structure-activity-guided scaffold optimization, advanced colon-targeted delivery systems, microbiome-stratified biomarker development, and systems-level target integration. Collectively, convergent preclinical evidence identifies plant-derived saponins as selectively multi-targeted candidates for UC; however, no purified plant-derived saponin has yet been tested in a randomised controlled trial in UC, and therapeutic claims must await evaluation against STRIDE-II targets such as faecal calprotectin normalisation, endoscopic healing and histological remission.
SN - 1663-9812
ER -