RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Peucedanum praeruptorum Dunn (PPD) was used to treat gastrointestinal disease in China before the Tang Dynasty, and it was considered a "Top-grade" herb in Shennong Bencaojing, known for its ability to relieve the stomach Qi and indigestion. AIM OF THE STUDY: Alcohol consumption can induce severe gastric mucosal injury that lacks effective and safe interventions. We aimed to investigate the gastroprotective effects of Peucedanum praeruptorum Dunn leaf (PPL) after bolting in alcohol-induced gastric damage in mice. MATERIALS AND METHODS: Mice were orally administered PPL aqueous extract at doses of 2.5, 5, and 10 g/kg for 5 consecutive days prior to the induction of gastric damage model with ethanol. Gastric tissue was stained by hematoxylin and eosin (H&E), and the levels of pro-inflammatory cytokines and oxidative stress indicators were determined using ELISA and RT-qPCR. RNA-seq was used to detect differentially expressed genes (DEGs) in the gastric tissue, while Western blotting was employed to measure the expressions of IL-17, TNF-a, and AKT pathways. RESULTS: Treatment with PPL alleviated alcohol-induced gastric damage in mice, whereas dried root (PPD) and stem (PPS) of Peucedanum praeruptorum Dunn had no gastroprotective function. The content of peucedanocoumarin I was higher in the dried PPL compared to PPD and PPS, with an increase in peucedanocoumarin I content in PPL after boiling. Additionally, PPL administration (5, 10 g/kg) decreased pro-inflammatory factors, such as interleukin-6 (IL-6), IL-8, IL-4, IL-1ß, IL-18, and tumor necrosis factor (TNF-a) in alcohol-induced gastric injury mice (p < 0.05), and improved oxidative stress markers, including superoxide dismutase enzymes (SOD), catalase (CAT), and malondialdehyde (MDA) (p < 0.05). RNA-seq data revealed that PPL treatment inhibited alcohol-induced inflammation-related signals, including IL-17 and TNF pathways, and restored alcohol-inhibited gastric digestive and metabolic functions, such as xenobiotics metabolism of cytochrome P450, and protein digestion and absorption pathways. Notably, treatment with PPL downregulated the expressions of IL-17 A, TNF-a, monocyte chemoattractant protein-1 (MCP-1), and AKT-phosphorylation induced by ethanol exposure (p < 0.05). Thus, the aqueous extract of PPL provided protection against alcohol-induced gastric injury by mitigating inflammation and oxidative stress in mice, suggesting a potential novel therapeutic approach for alcohol-induced gastric damage.