RESUMO
Context: Polygonum hydropiper L. (P. hydropiper) has outstanding clinical efficacy in treating both acute and chronic gastroenteritis. However, the definite mechanism remains unclear. Objective: This study aimed to explore the potential mechanisms of the total flavonoid of P. hydropiper (FPH) in stress-induced gastric mucosal damage (SGMD) rats through a combination of network pharmacology, molecular docking, and animal experiments. Methods: Network pharmacology and molecular docking were utilized to predict the potential mechanisms of FPH against SGMD. In experimental studies, SGMD rat models were established using water-immersion restraint stress (WIRS). FPH was administered at doses of 140, 70, and 35 mg/kg, with ranitidine serving as a positive control, through gavage once daily for 6 consecutive days after model establishment. Stomach and serum specimens were analyzed using HE staining, Western blotting, qPCR, and ELISA to investigate the protective mechanism of FPH in SGMD. Results: The network pharmacology analysis identified 16 active ingredients and 183 common targets, with potential pathways including PI3K/Akt, MAPK and Keap1/Nrf2. In vivo experiments demonstrated that FPH intervention alleviated SGMD pathological changes, reduced elevated serum IL-6 and TNF-α levels, and enhanced SOD and GSH activity in rats. Additionally, FPH increased the protein expression of p62, Nrf2, HO-1, PI3K, and p-Akt, along with mRNA levels of Nrf2, p62, and HO-1. Conclusions: FPH exerts a gastric mucosal protective effect by upregulating antioxidant gene expression through the PI3K/Akt and Keap1/Nrf2 pathways. This study provides an experimental basis for the potential clinical treatment of SGMD with the traditional Chinese medicine P. hydropiper.
RESUMO
The present study was conducted to investigate the underlying mechanisms and effective components of Polygonum hydropiper in ethanol-induced acute gastric mucosal lesions. The ethanol extract was purified on an AB-8 macroporous resin column and eluted with 60% ethanol and was then injected into the HPLC system for quantitative analysis. Sprague-Dawley rats were orally pretreated with P. hydropiper extract (PHLE; 50, 100, and 200 mg/kg) for 5 days and then absolute ethanol was administered to induce gastric mucosal damage. One hour after ethanol ingestion, the rats were euthanized and stomach samples were collected for biochemical analysis. Antioxidant enzymes and anti-inflammatory cytokines were quantified. Western blotting was used to detect the expression levels of proteins. Cell proliferation was assayed by CCK-8 assays. The proportion of total flavonoids in the final extract of P. hydropiper was 50.05%, which contained three major bioactive flavonoid constituents, including rutin, quercitrin, and quercetin. PHLE significantly increased cell viability and effectively protected human gastric epithelial cells-1 against alcohol-induced damage in vitro. PHLE pretreatment attenuated gastric mucosal injuries in a dose-dependent manner in rats, and increased the activity of superoxide dismutase, glutathione peroxidase, and glutathione, and decreased the levels of malondialdehyde in gastric tissue. Pretreatment with PHLE also reduced the generation of the pro-inflammatory cytokines tumor necrosis factor-α and interleukin-1ß in gastric tissue by downregulating the expression of nuclear factor-kappa B. PHLE exerted protective effects against gastric injury through antioxidant and anti-inflammatory pathways. Flavonoids might be the main effective components of P. hydropiper against gastric mucosal injury.