digestion and fermentation of ginseng pectic polysaccharide GPS-1 and attenuation of its product on oleic acid-induced oxidative stress in HepG2 cells.

2026-02-18
Frontiers in pharmacology 17
- Xiwen Sun
- Li Liu
- Wenbo Jiao
- Ting Ren
- Ran Zhao
- Zirui Tan
- Ziye Jiang
- Jing Wang
- Bo Li
- Xiaoyu Zhang
- Lili Jiao

PubMed: 41788794
DOI: 10.3389/fphar.2026.1758770

Background

Based on prior evidence that red ginseng pectin GPS-1 ameliorates T2DM in rats and modulates gut microbiota, we report for the first time that GPS-1 interacts with the gut microbiota of T2DM rats, as demonstrated through an in vitro digestion-fermentation model. This study reports for the first time that GPS-1 is key to its anti-T2DM efficacy. Building on prior findings that GPS-1 modulates gut microbiota in diabetic rats, we employed an in vitro digestion-fermentation model to demonstrate how GPS-1 is metabolized by specific bacteria into beneficial metabolites (e.g., short-chain fatty acids), thereby clarifying the causal pathway through which GPS-1 improves host metabolic health.

Materials and methods

GPS-1 was subjected to simulated salivary-gastrointestinal digestion in vitro, followed by fecal fermentation. Its physicochemical properties, including molecular weight (Mw), monosaccharide composition, uronic acid and reducing sugar content, were monitored. Short-chain fatty acids (SCFAs) production was quantified by GC-MS, and changes in gut microbiota composition were analyzed by 16S rRNA sequencing. The hepatoprotective effect of the fermented product (GPS-1-I48) was evaluated in oleic acid-treated HepG2 cells by measuring levels of triglyceride (TG), malondialdehyde (MDA), and the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px).

Results

GPS-1 was highly resistant to in vitro digestion, with no significant changes in Mw or carbohydrate composition. However, it was effectively degraded during fermentation, showing marked decreases in Mw and uronic acid content, a shift in monosaccharide profile, and an increase in reducing sugars. Fermentation of GPS-1 significantly modulated the gut microbiota structure of T2DM rats. It also markedly promoted the production of SCFAs. Consequently, the fermented product GPS-1-I48 exhibited significantly enhanced hepatoprotective activity, increasing SOD, CAT, and GSH-Px activities while reducing MDA and TG levels in HepG2 cells.

Conclusion

This study demonstrates that the hepatoprotective effect of GPS-1 depends on gut microbial fermentation. GPS-1 resists digestion but is degraded by the microbiota, enriching Bacteroides, boosting propionate and acetate production, and generating fermented products with enhanced antioxidant and lipid-lowering activity. These findings suggest that GPS-1 has potential as a prebiotic functional ingredient for improving intestinal health and regulating lipid metabolism.

Research Insights

Supplement	Health Outcome	Effect Type	Effect Size
Dried Yeast Fermentate	Improved Total Antioxidant Status	Beneficial	Moderate
Dried Yeast Fermentate	Increased Short-Chain Fatty Acid Production	Beneficial	Moderate
Dried Yeast Fermentate	Reduced Lipid Accumulation	Beneficial	Moderate

&lt;i&gt;In vitro&lt;/i&gt; digestion and fermentation of ginseng pectic polysaccharide GPS-1 and attenuation of its product on oleic acid-induced oxidative stress in HepG2 cells.