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Canolol Alleviates Ethanol-Induced Gastric Ulcer by Inhibiting p38 MAPK/NF-κB/NLRP3 Pathway
Congcong Ma1,2, Li Zhang3,4, Qingde Huang1,2
1Department of Nutriology, Oil Crops Research Institute, Chinese Academy of Agricultural Sciences, Wuhan 430062, China.
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.
Insights
Canolol, a compound from rapeseed oil, protects against stomach ulcers in rats. It reduces inflammation, boosts antioxidants, and prevents cell death by inhibiting key signaling pathways.
Area of Science:
- Gastroenterology
- Pharmacology
- Natural Product Chemistry
Background:
- Gastric ulcers (GU) are a widespread global health issue.
- Ethanol consumption is a significant risk factor for developing gastric ulcers.
- Natural compounds offer potential therapeutic avenues for digestive disorders.
Purpose of the Study:
- To investigate the gastroprotective effects of canolol against ethanol-induced gastric ulcers in a rat model.
- To elucidate the underlying molecular mechanisms of canolol's protective action.
Main Methods:
- Ethanol-induced gastric ulcer model in rats.
- Assessment of gastric mucosal damage (ulcer index, histopathology).
- Measurement of gastric wall mucus, NP-SH, heat shock protein 70, and mucosal blood flow.
- Quantification of pro-inflammatory (TNF-α, IL-1β, IL-6) and anti-inflammatory (IL-10) cytokines.
- Evaluation of antioxidant enzyme activities (SOD, CAT, GPx) and glutathione (GSH) levels.
- Assessment of apoptosis markers (TUNEL, BAX, caspase-3).
- Analysis of signaling pathway activation (p38 MAPK, NF-κB, NLRP3).
Main Results:
- Canolol pretreatment significantly reduced gastric ulcer index and improved histopathological scores.
- Canolol counteracted ethanol-induced disruption of mucosal defense mechanisms.
- Canolol alleviated gastric inflammation by modulating cytokine profiles and myeloperoxidase activity.
- Canolol enhanced antioxidant capacity and mitigated oxidative stress.
- Canolol suppressed ethanol-induced apoptosis in gastric mucosa.
- Canolol inhibited the p38 MAPK/NF-κB/NLRP3 signaling pathway.
Conclusions:
- Canolol exhibits significant gastroprotective effects against ethanol-induced gastric ulcers in rats.
- Canolol exerts its protective effects by reducing inflammation, oxidative stress, and apoptosis.
- The mechanism involves the inhibition of the p38 MAPK/NF-κB/NLRP3 pathway, highlighting its therapeutic potential.
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