Protective Effects of Lemon Leaf and Limonene against Indomethacin-Induced Gastric Ulcers in Rats: An In Vivo and In Silico Study

Abstract This paper aims to assess the possible protective effects of the lemon leaves and its main component, limonene, which is known for its active principles and health benefits, against indomethacin-induced oxidative stress in the rats. In this study, the rats were given the ethanol extract from the lemon (Citrus L.) leaf and famotidine, a medication used for treating duodenal and gastric ulcers. The extracts (0.25, 0.5, and 1 g/kg) and/or famotidine (20 mg/kg) were administered to the treated rats via oral gavage at the doses determined for each group. Five minutes later, the rats were orally given a single dose of indomethacin (25 mg/kg). After six hours, the stomach tissues of the rats were collected for biochemical analysis. The treatment significantly improved gastric ulcer conditions by reducing oxidative stress, a key contributor to ulcer formation. Notably, the rats that received the highest dose of the extract exhibited significantly reduced MDA levels, an indicator of oxidative stress, in comparison to the control group. Furthermore, these rats showed a significant increase in SOD activities and GSH levels. The present study also focused on the mechanism underlying the gastroprotective action of limonene, a primary component of Citrus L., against PGE2, Na+/K+-ATPase, and H+/K+-ATPase under in silico conditions. The findings from this study might have significant implications for treating numerous global health disorders due to the antioxidant properties of the ethanol extract from the lemon leaf.