The protective effect of tangeretin and pomegranate separately and in combination on ethanol-induced acute gastric ulcer model

Purpose: This study was designed to find an answer to the question, "Is it beneficial to use pomegranate (POM) and tangeretin (TAN) separately or in combination, for the prevention of acute gastric ulcer?". Materials and Methods: The gastroprotective effect of tangeretin and pomegranate was determined by measuring the levels of the selected inflammatory cytokines [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β and IL-10], lipid peroxides, and enzymatic activities of antioxidants in gastric tissue samples. Results: When all groups are written as control, gastric ulcer, POM+EtOH, TAN+EtOH and POM+TAN+EtOH, respectively; IL-1β cytokine levels were measured as 0.147, 0.24, 0.228, 0.195 and 0.182 pg/g protein. IL-6 levels; 16,857, 25,923, 19,797, 18,838 and 17,896 pg/mg protein. TNF-α levels were 39,916, 49.97, 44,678, 41,673 and 40,844 pg/mg protein. Finally, IL-10 levels were measured as 33,496, 28,071, 29,693, 30,073 and 30,008 pg/mg protein. SOD activities were determined as 18,038, 13,731, 15,506, 14,439, and 15,943. CAT activities were 674,638, 639,964, 673,382, 664,691, and 671,203. Protein carbonyl levels were measured as 26,799, 40,30, 33,052, 34,579 and 32,79. Finally, MDA levels were found as 5,239, 9,814, 6,695, 5,771 and 5,836. Briefly, POM and TAN showed their antioxidant functions by decreasing the levels of malondialdehyde (MDA), and protein carbonyl and increasing the activity of superoxide dismutase (SOD) and catalase (CAT). And also, these protective agents exhibited their anti-inflammatory functions by decreasing the content of TNF-α, IL-6, and IL-1β, and increasing the IL-10 levels. Conclusion: Tangeretin and pomegrenate have a potential gastroprotective effect against ethanol-induced acute gastric ulcer and that the combined treatment is more beneficial than the effect of POM or TAN alone. In addition, this effect is thought to be due to the fact that both selected flavonoids can show a synergistic effect, reducing the levels of inflammation parameters and increasing antioxidant levels.

[1]  K. Msaada,et al.  Antioxidant potentialities and gastroprotective effect of Reichardia picroides extracts on Ethanol/HCl induced gastric ulcer rats , 2023, International journal of environmental health research.

[2]  M. Kılınç,et al.  In twin pregnancies, zinc and iron decreased, while copper increased minimally , 2022, Middle Black Sea Journal of Health Science.

[3]  Murilo Piologo Ciciliato,et al.  Anti-Inflammatory Effect of Vanillin Protects the Stomach against Ulcer Formation , 2022, Pharmaceutics.

[4]  T. Homma,et al.  Superoxide Radicals in the Execution of Cell Death , 2022, Antioxidants.

[5]  Hao Zhang,et al.  The global, regional and national burden of peptic ulcer disease from 1990 to 2019: a population-based study , 2022, BMC Gastroenterology.

[6]  I. Bektas,et al.  Protective effects of rosmarinic acid against azoxymethane‐induced colorectal cancer in rats , 2021, Journal of biochemical and molecular toxicology.

[7]  A. Ashraf,et al.  Tangeretin ameliorates bisphenol induced hepatocyte injury by inhibiting inflammation and oxidative stress , 2021, Saudi journal of biological sciences.

[8]  T. Aljutaily,et al.  Gastroprotective Effects of Spirulina platensis, Golden Kiwifruit Flesh, and Golden Kiwifruit Peel Extracts Individually or in Combination against Indomethacin-Induced Gastric Ulcer in Rats , 2021, Nutrients.

[9]  Guojin Gong,et al.  Gastroprotective effect of cirsilineol against hydrochloric acid/ethanol-induced gastric ulcer in rats , 2021, The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology.

[10]  Jinghui Sun,et al.  Protective Effects of Anwulignan against HCl/Ethanol-Induced Acute Gastric Ulcer in Mice , 2021, Evidence-based complementary and alternative medicine : eCAM.

[11]  H. Kelebek,et al.  Elucidation of Volatiles, Anthocyanins, Antioxidant and Sensory Properties of cv. Caner Pomegranate (Punica granatum L.) Juices Produced from Three Juice Extraction Methods , 2021, Foods.

[12]  D. Elgamal,et al.  Interplay of Biochemical, Genetic, and Immunohistochemical Factors in the Etio-Pathogenesis of Gastric Ulcer in Rats: A Comparative Study of the Effect of Pomegranate Loaded Nanoparticles Versus Pomegranate Peel Extract , 2021, Frontiers in Physiology.

[13]  El‐Shaimaa A. Arafa,et al.  Therapeutic Implications of a Polymethoxylated Flavone, Tangeretin, in the Management of Cancer via Modulation of Different Molecular Pathways , 2021, Advances in pharmacological and pharmaceutical sciences.

[14]  V. Assadollahi,et al.  The effects of pomegranate peel extract on the gene expressions of antioxidant enzymes in a rat model of alloxan-induced diabetes , 2021, Archives of physiology and biochemistry.

[15]  A. Çelikkol,et al.  Royal jelly attenuates gastric mucosal injury in a rat ethanol-induced gastric injury model , 2020, Molecular Biology Reports.

[16]  Sally E Abu-Risha,et al.  The potential beneficial effects of sildenafil and diosmin in experimentally-induced gastric ulcer in rats , 2020, Heliyon.

[17]  I. Ahmed,et al.  Carvedilol safeguards against aspirin-induced gastric damage in rats , 2020, Human & experimental toxicology.

[18]  Ş. Çetinel,et al.  Potent therapeutic effects of ruscogenin on gastric ulcer established by acetic acid. , 2020, Asian journal of surgery.

[19]  M. Güler,et al.  Agomelatine prevents indomethacin-induced gastric ulcer in rats , 2020, Pharmacological Reports.

[20]  I. Fatemi,et al.  Ameliorating effect of troxerutin in unilateral ureteral obstruction induced renal oxidative stress, inflammation, and apoptosis in male rats , 2020, Naunyn-Schmiedeberg's Archives of Pharmacology.

[21]  M. Rahmani,et al.  The effect of oleuropein on unilateral ureteral obstruction induced-kidney injury in rats: the role of oxidative stress, inflammation and apoptosis , 2019, Molecular Biology Reports.

[22]  E. A. Elsayed,et al.  Antiulcerogenic effect of Cuphea ignea extract against ethanol-induced gastric ulcer in rats , 2019, BMC Complementary and Alternative Medicine.

[23]  U. Abdelmohsen,et al.  Gastro-Protective and Anti-Oxidant Potential of Althaea officinalis and Solanum nigrum on Pyloric Ligation/Indomethacin-Induced Ulceration in Rats , 2019, Antioxidants.

[24]  E. Tamaddonfard,et al.  Safranal, a constituent of saffron, exerts gastro-protective effects against indomethacin-induced gastric ulcer. , 2019, Life sciences.

[25]  M. Shahzad,et al.  Oxyresveratrol ameliorates ethanol-induced gastric ulcer via downregulation of IL-6, TNF-α, NF-ĸB, and COX-2 levels, and upregulation of TFF-2 levels. , 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[26]  O. Akinloye,et al.  First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): Their fundamental role in the entire antioxidant defence grid , 2018, Alexandria Journal of Medicine.

[27]  Xu Liu,et al.  Antichronic Gastric Ulcer Effect of Zinc-Baicalin Complex on the Acetic Acid-Induced Chronic Gastric Ulcer Rat Model , 2018, Gastroenterology research and practice.

[28]  M. Vaiyapuri,et al.  Orientin, a flavanoid, mitigates 1, 2 dimethylhydrazine-induced colorectal lesions in Wistar rats fed a high-fat diet , 2018, Toxicology reports.

[29]  S. Yumnam,et al.  Identification of a novel biomarker in tangeretin-induced cell death in AGS human gastric cancer cells , 2018, Oncology reports.

[30]  Chi-Tang Ho,et al.  Immature Citrus reticulata Extract Promotes Browning of Beige Adipocytes in High-Fat Diet-Induced C57BL/6 Mice. , 2018, Journal of agricultural and food chemistry.

[31]  S. Mousa,et al.  Protective Effects of Miswak (Salvadora persica) against Experimentally Induced Gastric Ulcers in Rats , 2018, Oxidative medicine and cellular longevity.

[32]  H. Tae,et al.  Anti-Inflammatory and Gastroprotective Roles of Rabdosia inflexa through Downregulation of Pro-Inflammatory Cytokines and MAPK/NF-κB Signaling Pathways , 2018, International journal of molecular sciences.

[33]  A. Wojdyło,et al.  Influence of osmotic dehydration pre-treatment and combined drying method on physico-chemical and sensory properties of pomegranate arils, cultivar Mollar de Elche. , 2017, Food chemistry.

[34]  Chi-Tang Ho,et al.  Pharmacokinetics, bioavailability, tissue distribution and excretion of tangeretin in rat , 2017, Journal of food and drug analysis.

[35]  K. Amirshahrokhi,et al.  Methylsulfonylmethane is effective against gastric mucosal injury. , 2017, European journal of pharmacology.

[36]  Gulzar Ahmad Nayik,et al.  Citrus peel as a source of functional ingredient: A review , 2016, Journal of the Saudi Society of Agricultural Sciences.

[37]  K. Hahm,et al.  Quality of healing of gastric ulcers: Natural products beyond acid suppression. , 2014, World journal of gastrointestinal pathophysiology.

[38]  X. Niu,et al.  Protective effect of chelerythrine against ethanol-induced gastric ulcer in mice. , 2014, Chemico-biological interactions.

[39]  H. Matsui,et al.  The pathophysiology of non-steroidal anti-inflammatory drug (NSAID)-induced mucosal injuries in stomach and small intestine , 2011, Journal of clinical biochemistry and nutrition.

[40]  Y. Sun,et al.  A simple method for clinical assay of superoxide dismutase. , 1988, Clinical chemistry.

[41]  N. Ilhan,et al.  The therapeutic effects of thalidomide and etanercept on septic rats exposed to lipopolysaccharide. , 2019, Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTES.

[42]  Chi-Tang Ho,et al.  Bioactive Constituents , Metabolites , and Functions Antioxidant Protection of Nobiletin , 5-Demethylnobiletin , Tangeretin , and 5-Demethyltangeretin from Citrus Peel in Saccharomyces cerevisiae , 2018 .

[43]  Ahmet Arslan,et al.  WSSPAS: An Interactive Web Application for Sample Size and Power Analysis with R Using Shiny , 2018 .