The Gastroprotective Effect of Naringenin against Ethanol-Induced Gastric Ulcers in Mice through Inhibiting Oxidative and Inflammatory Responses

• Published in: International journal of molecular sciences Vol. 22; no. 21; p. 11985
• Main Authors: Li, Wei-Sung, Lin, Shih-Chao, Chu, Chien-Hui, Chang, Yu-Kang, Zhang, Xiang, Lin, Chi-Chien, Tung, Yu-Tang
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 05.11.2021; MDPI
• Subjects: Acidity; Animals; Anti-Ulcer Agents - pharmacology; Antioxidants; Central Nervous System Depressants - toxicity; Citrus fruits; Cyclooxygenase-2; Cytokines; Disease Models, Animal; Drugs; Edema; Epithelial cells; Epithelium; Ethanol; Ethanol - toxicity; Flavanones - pharmacology; gastric ulcers; Hemorrhage; In vivo methods and tests; Inflammation; Inflammation - chemically induced; Inflammation - drug therapy; Inflammation - immunology; Inflammation - pathology; Interleukin 6; Interleukin 8; Kinases; Leukocytes; Male; Malondialdehyde; MAP kinase; Medicin och hälsovetenskap; Mice; Mice, Inbred BALB C; Naringenin; Natural products; Neutrophils; NF-kappa B - metabolism; NF-κB protein; Nitric oxide; Nitric-oxide synthase; Oral administration; Oxidative stress; Oxidative Stress - drug effects; Peroxidase; Phosphorylation; Physiology; Pretreatment; Protein kinase; Proteins; Stomach Ulcer - chemically induced; Stomach Ulcer - drug therapy; Stomach Ulcer - metabolism; Stomach Ulcer - pathology; Tangerines; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Ulcers; naringenin; gastric ulcers; inflammation; ethanol; oxidative stress
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms222111985

Naringenin is a major flavanone found in grapes, tangelos, blood oranges, lemons, pummelo, and tangerines. It is known to have anti-inflammatory, antioxidant, anticancer, antimutagenic, antifibrogenic, and antiatherogenic pharmacological properties. This study aims to investigate the anti-inflammatory effects of naringenin in ethanol-induced gastric damage in vivo and ethanol-stimulated KATO III cells in vitro. Our results showed that pretreatment with naringenin significantly protected mice from ethanol-induced hemorrhagic damage, epithelial cell loss, and edema with leucocytes. It reduced gastric ulcers (GU) by suppressing ethanol-induced nuclear factor-κB (NF-κB) activity and decreasing the levels of nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and myeloperoxidase (MPO). In addition, pretreatment with naringenin might inhibit the secretion of TNF-α, IL-6, and IL-8, as well as the proteins cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) via the suppression of NF-κB and mitogen-activated protein kinase (MAPK) signaling in ethanol-stimulated stomach epithelial KATO III cells. Together, the results of this study highlight the gastroprotective effect of naringenin in GU of mice by inhibiting gastric secretion and acidity, reducing inflammation and oxidative stress, suppressing NF-κB activity, and restoring the histological architecture. These findings suggested that naringenin has therapeutic potential in the alleviation of ethanol-induced GU.