Canolol Alleviates Ethanol-Induced Gastric Ulcer by Inhibiting p38 MAPK/NF-κB/NLRP3 Pathway

Abstract

Gastric ulcer (GU) is among the most prevalent digestive disorders globally. This study investigates the protective effects of canolol, a natural phenolic compound derived from crude rapeseed oil, on ethanol-induced GU in rats. Our results demonstrated that canolol pretreatment notably reduced gastric mucosal damage, as evidenced by lower ulcer indices and improved histopathological scores. Ethanol exposure severely disrupted the gastric mucosal defense systems, characterized by reduced gastric wall mucus secretion, lower NP-SH levels, suppressed heat shock protein 70 expression, and decreased gastric mucosal blood flow; however, these effects were counteracted by canolol pretreatment. Canolol also alleviated ethanol-induced inflammation by reducing the levels of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), enhancing the level of the anti-inflammatory cytokine (IL-10), and normalizing myeloperoxidase activity in the gastric mucosa. Additionally, canolol enhanced antioxidant defenses by increasing the activities of antioxidant enzymes (SOD, CAT, and GPx) and the GSH level, thereby mitigating ethanol-induced oxidative stress in the stomach. Moreover, canolol suppressed ethanol-induced apoptosis in the gastric mucosa, evidenced by a decrease in TUNEL-positive areas and downregulation of the expression of apoptotic markers BAX and caspase-3. Mechanistically, canolol substantially reduced the activities of p38 MAPK and NF-κB, consequently preventing NLRP3 activation. These findings indicate that canolol has potential benefits in preventing the onset and progression of ethanol-induced GU by inhibiting the p38 MAPK/NF-κB/NLRP3 pathway.