Asiatic acid attenuates indomethacin-induced gastric ulcer in rats: Association with reduced IFN-γ/JAK-1/STAT3 signaling.

Gastric ulceration is a common dose-limiting adverse effect associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs). Asiatic acid (AA) is a naturally occurring pentacyclic triterpenoid that has been reported to possess antioxidant, anti-inflammatory, and healing properties. The present study investigated the potential protective effect of AA against indomethacin-induced gastric ulceration in rats. Male rats were divided into five groups: control, indomethacin (50 mg/kg), indomethacin + AA (25 mg/kg), indomethacin + AA (50 mg/kg), and indomethacin + omeprazole (30 mg/kg). Indomethacin administration produced marked gastric mucosal injury, whereas pretreatment with AA significantly reduced ulceration as confirmed by a reduction in the macroscopic ulcer index and by histopathological examination. AA also reduced lipid peroxidation and prevented the depletion of endogenous antioxidant enzymes, indicating a protective antioxidant effect. In addition, AA suppressed the immuno-expression of cyclooxygenase-2, tumor necrosis factor-α, interleukin-6, and nuclear factor-κB, suggesting a significant anti-inflammatory action. AA was also associated with a reduction in the indomethacin-induced increase in the immuno-expression of interferon-γ (IFN-γ), JAK-1, and phosphorylated STAT3. At the molecular level, AA decreased the mRNA expression of the pro-apoptotic gene Bax and increased the expression of the anti-apoptotic gene Bcl-2. These findings indicate that AA ameliorates indomethacin-induced gastric ulceration in rats. This gastroprotective effect is associated with antioxidant, anti-inflammatory, and anti-apoptotic activities, as well as downregulation of the IFN-γ/JAK-1/STAT3 signaling pathway.