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

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.