Mechanisms of ginsenoside Rg1 in preventing ETEC‑induced diarrhea: Maintaining ileal integrity and eliminating inflammation

Abstract

Background: Enterotoxigenic Escherichia coli (ETEC) can cause severe watery diarrhea and rapid dehydration or death of newborn animals, resulting in significant economic losses of animal farms around the world. The endotoxin produced by ETEC usually causes inflammation and damage to the integrity of the intestinal mucosa, which leads to the destruction of intestinal homeostasis. To date, ETEC infections have been treated widely using drugs and antibiotics. Unfortunately, after high-dose or long-term antibiotic treatment, ETEC might develop drug or antibiotic resistance, and the animal products might also contain their residues. Therefore, the development of antibiotic substitutes has been explored widely by scholars. The main phytocomponent of Ginseng is ginsenoside Rg1 (GRg1), which has shown anti‐inflammatory properties in animal models and cell lines.Methods: Mice were infected with ETEC after 14 days of treatment with different doses of GRg1, and the diarrhea index, ileal pathological changes, and inflammatory factors in plasma were compared. Changes to the proteins in the ileum were assessed using proteomics.Results: ETEC challenge not only increased the serum content of inflammatory cytokines, such as interleukin (IL) 1β, IL6, and tumor necrosis factor alpha (TNFα), (P < 0.05), but also induced pathological changes in the ileum such as reduction of villus height, crypt depth (P < 0.05), and inflammatory cell infiltration. However, different doses of GRg1 treatment significantly reversed the above changes, with no significant dose dependence (P > 0.05). Proteomic analysis identified 55 differentially abundant proteins in the ileum of ETEC-infected mice treated with and without GRg1. Bioinformatic analysis indicated that these proteins were involved in 15 signaling pathways, particularly, the complement and coagulation cascade pathway and the platelet activation pathway. Western blotting identified that the key proteins complement C3, fibrinogen (Fg)A, FgB and FgG in these signaling pathways were significantly downregulated by GRg1 (P < 0.05), which was consistent with the proteomic analysis.Conclusion: GRg1 alleviates ETEC diarrhea in mice by eliminating the infection‑related inflammatory reaction and maintaining the integrity of intestinal mucosa.

Protective effect of Limosilactobacillus reuteri‐fermented yogurt on mouse intestinal barrier injury induced by enterotoxigenic Escherichia coli

“…The main signs of intestinal injury induced by ETEC are intestinal inflammation and tissue destruction, shortened jejunal villi, increased crypt depth and inflammatory symptoms such as neutrophil infiltration and destruction of crypts in the colon. 40 After H&E staining, the villus length and crypt depth of the jejunum were measured, and then the colon histological score was determined. The colon histological score of the Ctr group indicated no inflammation.…”