Ipomoea carnea mitigates ethanol-induced ulcers in irradiated rats via Nrf2/HO-1 pathway: an in vivo and in silico study.

The aim of this study was to investigate the potential of Ipomoea carnea flower methanolic extract (ICME) as a natural gastroprotective therapy against ethanol-induced gastric ulcers, particularly in individuals exposed to ionizing radiation (IR). The study focused on the Nrf2/HO-1 signaling pathway, which plays a crucial role in protecting the gastrointestinal mucosa from oxidative stress and inflammation. Male Wistar rats were divided into nine groups, the control group received distilled water orally for one week, while other groups were treated with ethanol to induce stomach ulcers, IR exposure, omeprazole, and different doses of ICME in combination with ethanol and/or IR. The study conducted comprehensive analyses, including LC-HRESI-MS/MS, to characterize the phenolic contents of ICME. Additionally, the Nrf2/HO-1 pathway, oxidative stress parameters, gastric pH, and histopathological changes were examined. The results showed that rats treated with IR and/or ethanol exhibited histopathological alterations, increased lipid peroxidation, decreased antioxidant enzyme activity, and reduced expression levels of Nrf2 and HO-1. However, pretreatment with ICME significantly improved these parameters. Phytochemical analysis identified 39 compounds in ICME, with flavonoids, hydroxybenzoic acids, and fatty acids as the predominant compounds. Virtual screening and molecular dynamics simulations suggested that ICME may protect against gastric ulceration by inhibiting oxidative stress and inflammatory mediators. In conclusion, this study demonstrates the potential of ICME as a natural gastroprotective therapy for preventing gastric ulcers. These findings contribute to the development of novel interventions for gastrointestinal disorders using natural plant extracts particularly in individuals with a history of radiation exposure.

Co-treatment with Esculin and erythropoietin protects against renal ischemia-reperfusion injury via P2X7 receptor inhibition and PI3K/Akt activation.

Renal ischemia/reperfusion (RI/R) is a critical clinical outcome with slightly reported improvement in mortality and morbidity. Effective therapies are still crucially required. Accordingly, the therapeutic effects of esculin (ESC, LCESI-MS/MS-isolated compound from Vachellia farnesiana flowers extract, with reported P2X7 receptor inhibitor activity) alone and in combination with erythropoietin (EPO) were investigated against RI/R injury and the possible underlying mechanisms were delineated. ESC and EPO were administered for 7 days and 30 min prior to RI, respectively. Twenty-four hour following reperfusion, blood and kidney samples were collected. Results revealed that pretreatment with either ESC or EPO reduced serum nephrotoxicity indices, renal oxidative stress, inflammatory, and apoptosis markers. They also ameliorated the renal histopathological injury on both endothelial and tubular epithelial levels. Notably, ESC markedly inhibited P2X7 receptors and NLRP3 inflammasome signaling (downregulated NLRP3 and Caspase-1 gene expressions), whereas EPO significantly upregulated PI3K and Akt gene expressions, also p-PI3K and p-Akt levels in renal tissues. ESC, for the first time, demonstrated effective protection against RI/R-injury and its combination with EPO exerted maximal renoprotection when compared to each monotherapy, thereby representing an effective therapeutic approach via inhibiting oxidative stress, inflammation, renal tubular and endothelial injury, apoptosis, and P2X7 receptors expression, and activating PI3K/Akt pathway.