LC-MS profiling and antiulcer mechanisms of Rumex pictus extract and its isolated emodin-8-O-β-glucoside against ethanol-induced gastric damage.

Abstract

Peptic ulcer disease is considered a global health concern, commonly caused by Helicobacter pylori infection, chronic NSAID use, and ethanol-induced gastric mucosal injury. Although proton pump inhibitors and anti-secretory drugs are effective, their prolonged use increases risks of fractures, infections, and nutrient deficiencies, highlighting the urgent need for safer alternatives. The Rumex genus, particularly R. pictus Forssk. aerial parts, has long been employed in Middle Eastern traditional medicine to alleviate gastric inflammation and ulcers. The antiulcer bioassays of the 70% aqueous methanolic R. pictus extract (RPE) (150-300 mg/kg) and its isolated emodin-8-O-β-glucoside (EGL) (15-30 mg/kg) were assessed using an in vivo ethanol-induced gastric injury model. Additionally, LC-ESI-MS/MS was used to identify the phenolic constituents from RPE. 42 Metabolites were identified from LC-ESI-MS/MS profiling of RPE including phenolic acids (e.g. caffeic, ferulic, chlorogenic), flavonoid C- and O-glycosides (e.g. orientin, isoorientin, vitexin, isovitexin, hyperoside), and anthraquinones (e.g. emodin, chrysophanol, physcion, and their glycosides). Both RPE and EGL restored gastric antioxidant defenses by elevating glutathione and glutathione-S-transferase while lowering MDA levels, downregulated pro-inflammatory cytokines: TNF-α and IL-1β, and enhanced cytoprotective PGE2 production. Notably, the higher dose of EGL (30 mg/kg) produced superior gastroprotection as it demonstrated greater suppression of oxidative stress and cytokine release alongside enhanced mucosal regeneration. Histopathological analysis further confirmed reduced hemorrhage, edema, and epithelial necrosis, particularly at higher doses. These findings establish RPE and EGL as promising gastroprotective candidates, reinforcing their ethnomedicinal value and supporting further development as safer alternatives for peptic ulcer management.