Luteolin ameliorates Indomethacin-Induced Gastric Ulcer in Rats via Activation of Nrf2/HO-1 Pathway

Abstract

Objectives: To examine the protective impacts of luteolin on gastric ulcers caused by indomethacin (IND), as well as to elucidate the underlying processes responsible for these effects. Background: Gastric ulcer is a communal gastrointestinal disorder induced by an imbalance between protective as well as detrimental factors. Methods: This experimental study used 30 male Wister albino rats categorized into three groups (n=10/group): Control, ulcer, as well as Ulcer+Lut groups. At the end of the study, rats underwent gastric acidity and gastric lesions measurement, in addition to an assessment of malondialdehyde (MDA), interleukin 1β (IL-1β), gastric tumor necrosis factor-alpha (TNF-α), superoxide dismutase (SOD), and prostaglandin E2 (PGE2). Additionally, real-time PCR assessment of nuclear factor erythroid 2–related factor 2 (Nrf2), as well as gastric hemeOxygenase-1 (HO-1) gene expression, were assessed. Similarly, the stomach was subjected to histological and immunohistochemistry evaluation. Results: The study revealed that administering IND led to the progression of gastric ulcers, as evidenced by a notable rise in the gastric ulcer index (GUI), gastric TNF-α, IL-1β, and MDA. Additionally, it induced a substantial elevation in gastric acidity and decrease in PGE2 and SOD levelsbesides downregulation of gastric HO-1 and Nrf2 gene expression and upregulated gastric Bax and NF-κB immunoreaction. Luteolin supplementation reversed these changes induced by IND. Conclusion: Luteolin had the potential to be a valuable antiulcer agent., where it could relieve the gastric ulcer caused using IND in rats via antiapoptotic, anti-inflammatory, antioxidant, and upregulated Nrf2/HO-1 pathway mechanisms.