Work

Eucalyptol attenuates indomethacin-induced gastric ulcers in rats by modulating the ICAM-1, eNOS and COX/LOX pathways: Insights from in silico, in vitro and in vivo approaches

Year: 2025

Type: article

Abstract: In order to evaluate anti-inflammatory role of eucalyptol (100, 200, and 400 mg/kg orally), inflammation was induced in rats using 0.1 ml of histamine and 0.1 ml of formaldehyde. Furthermore, in vivo gastroprotective potential of eucalyptol (100, 200 and 400 mg/kg) was determined via the intraperitoneal injection of 25 mg/kg indomethacin as an ulcerative agent and omeprazole (30 mg/kg) orally as a standard. Estimation of biochemical (PGE 2, ICAM-1, COX-I, COX-II, eNOS and 5-LOX) and oxidative stress (SOD, CAT, GSH, and MDA) markers were carried out in gastric tissues using ELISA. The morphological and histopathological features of the gastric tissues were studied. In vitro , eucalyptol stabilized red blood cell membranes and inhibited protein denaturation , with the maximum effect observed at a concentration of 6400 μg/mL. Eucalyptol significantly reduced rat paw edema in histamine- and formaldehyde-induced inflammation models. It increased gastric PGE 2, COX-I and eNOS levels, and decreased COX-II, 5-LOX and ICAM-1. Eucalyptol reduced ulcer indices and improved histopathological changes. Eucalyptol also increased antioxidants levels with decreased MDA levels in isolated rat stomach tissues. Therefore, eucalyptol shows gastroprotective effects against histamine- and formaldehyde induced inflammation and indomethacin-induced gastric ulcers through the modulation of the COX/LOX, ICAM-1, eNOS pathways and oxidative stress biomarkers. • In vitro study of Eucalyptol showed inhibiting protein denaturation, with the peak effect at a concentration of 6400 μg/mL. • Eucalyptol reduced rat paw edema in the histamine- and formaldehyde-induced inflammation models. • Eucalyptol reduced indomethacin-induced gastric ulcers indices and improved histopathological changes. • Eucalyptol increased the gastric PGE 2, COX-I and eNOS levels, while decreased the COX-II, 5-LOX and ICAM-1 levels. • The protective effects of eucalyptol are possibly through modulating the COX/LOX, ICAM-1, eNOS pathways and oxidative stress.

Source: Food and Chemical Toxicology

DOI: 10.1016/j.fct.2025.115319