The Potential Anti-ulcerogenic Effects of Baicalein and/or Empagliflozin in Induced Gastric Ulcer in Rats: Modulating HO-1/SIRT1 / HMGB1 signaling Pathway

Background: Gastric ulcer is one of the most ubiquitous gastrointestinal tract disorders, causing high morbidity. The goal of this study was to explore at the mechanistic effects of Baicalein (BA) and/or Empagliflozin (EMP) treatment on gastric ulcer caused by indomethacin and prednisolone, with an emphasis on the role of the HO-1/SIRT1 / HMGB1 signaling pathway.Material and methods: Fifty adult albino rats were allocated into 5 equal groups: control, ulcer (Prednisolone 10mg/kg for 6 days followed by indomethacin as single oral dose 30 mg/kg), BA (30 mg/kg), EMP (10 mg/kg), and BA + EMP groups. The volume of gastric juice, pH, free and total acidity was estimated. The gene expression of HO-1 and SIRT1 in gastric tissues was assessed by qRT PCR. Biochemical analysis of gastric tissues homogenates including HMGB-1, PGE2 & nitrites levels was performed. Assay of inflammatory markers and redox status were detected. Additionally, histological, scanning electron microscopic and immunohistochemical analyses were determined.Results: After 4 weeks of treatment, there was remarkable improvement of the histological architecture of rat gastric tissues. Upregulation of HO-1 and SIRT1 gene expression, as well as a decrease in HMGB1 level, resulted in improved inflammatory and oxidative stress biomarkers. Furthermore, immunohistochemical analysis revealed increase in Bcl-2 expression and decreased expression of Bax in the treated groups. Conclusion: Concurrent usage of BA & EMP against gastric ulcer in rats could be related to the interaction of their anti-oxidant, antiinflammatory, and anti-apoptotic activities via modulation of HO-1/SIRT1 / HMGB1 signaling pathway.. Keywords