Related Experiment Video
Updated: Jul 15, 2026
Assessment of Gut Barrier Integrity in Mice Using Fluorescein-Isothiocyanate-Labeled Dextran
Published on: November 18, 2022
Polygonatum sibiricum polysaccharide ameliorates intestinal barrier dysfunction in aging mice via gut
Peiyao Guan1, Xin Zeng1, Ziye Li2
1Department of Nutrition Science and Food Hygiene, Xiangya School of Public Health, Central South University, Hunan, 410013, Changsha, China.
Background:
Intestinal barrier dysfunction is a critical pathological feature of aging-related diseases. Polygonatum sibiricum polysaccharide (PSP), a natural bioactive compound, has been reported to possess microbiota-regulatory and immunomodulatory properties; however, its protective effects against aging-induced intestinal barrier injury and the underlying mechanisms remain unclear.
Purpose:
This study aimed to investigate the protective effects of PSP on age-related intestinal barrier dysfunction and to elucidate the underlying mechanisms, with a particular focus on the microbiota-metabolism-immunity axis.
Study Design:
A combination of in vivo and in vitro experiments, together with multi-omics analyses and network pharmacology, was employed to systematically evaluate the effects and mechanisms of PSP in aging-associated intestinal barrier injury.
Methods:
Ultraviolet (UV) spectroscopy, gel permeation chromatography (GPC), high-performance liquid chromatography-mass spectrometry (HPLC-MS), and Fourier-transform infrared spectroscopy (FT-IR) were adopted to comprehensively characterize the purity and detailed structural profiles of PSP. Naturally aged mice were orally administered PSP (400 mg/kg) to assess intestinal barrier integrity, permeability, inflammatory responses, and gut microbiota composition. In vitro, D-galactose (D-gal)-induced senescent Caco-2 cells were treated with PSP (100, 200, and 400 μg/ml) to evaluate cellular senescence, tight junction protein expression, and pro-inflammatory cytokine production. Network pharmacology analysis was conducted to predict key signaling pathways involved, followed by experimental validation and reverse confirmation using a TLR4 agonist.
Results:
Characterization by UV spectroscopy and GPC confirmed the purity and molecular weight distribution of PSP, respectively; monosaccharide analysis revealed it was mainly composed of glucose, mannose, and galactose, and FT-IR identified its characteristic functional groups. In naturally aged mice, PSP administration significantly improved intestinal barrier integrity, reduced intestinal permeability, alleviated inflammatory responses, and reshaped gut microbiota composition. In Caco-2 cells, PSP dose-dependently attenuated D-gal-induced cellular senescence, restored tight junction protein expression, and suppressed pro-inflammatory cytokine production. Network pharmacology analysis identified the TLR4/NF-κB signaling pathway as a potential key target of PSP, which was further confirmed by both in vivo and in vitro experiments.
Conclusions:
Collectively, these findings demonstrate that PSP alleviates aging-associated intestinal barrier dysfunction through multi-level regulation involving the microbiota-metabolism-immunity axis and supports its potential as a natural therapeutic candidate for anti-aging interventions.
