Etanol ile indüklenmiş akut gastrik ülser modelinde tangeretin ve pomegrenatın ayrı ayrı ve kombinasyon halinde koruyucu etkisi

Year 2023, Volume: 48 Issue: 3, 859 - 867, 30.09.2023

Solmaz Susam , Nevin İlhan , Fatma Tedik , Buket Berk , Ayşe Şebnem İlhan

https://doi.org/10.17826/cumj.1314757

Abstract

Amaç: Bu çalışma, "Akut gastrik ülserinden korunma konusunda pomegrenat ve tangeretinin ayrı ayrı veya birlikte kullanılması yararlı mıdır?" sorusuna cevap bulmak amacıyla tasarlanmıştır.
Gereç ve Yöntem: Mide dokusunda tangeretin and pomegranatın gastroprotektif etkisi, seçili inflamatuar sitokinler [tümör nekroz faktörü-α (TNF-α), interlökin-6 (IL-6), IL-1β ve IL-10)], lipid peroksit düzeyleri ve enzimatik antioksidan aktiviteleri ölçülerek değerlendirildi.
Bulgular: Tüm gruplar kontrol, gastrik ülser, POM+EtOH, TAN+EtOH ve POM+TAN+EtOH şeklinde sırasıyla yazıldığında; IL-1β sitokin düzeyleri: 0,147, 0,24, 0,228, 0,195 ve 0,182 pg/g protein olarak ölçüldü. IL-6 düzeyleri; 16,857, 25,923, 19,797, 18,838 ve 17,896 pg/ mg protein idi. TNF-α düzeyleri 39,916, 49,97, 44,678, 41,673 ve 40,844 pg/mg protein idi. Son olarak IL-10 düzeyleri ise 33,496, 28,071, 29,693, 30,073 ve 30,008 pg/mg protein olarak ölçüldü. SOD aktiviteleri 18,038, 13,731, 15,506, 14,439, 15,943 olarak tayin edildi. CAT aktiviteleri ise 674,638, 639,964, 673,382, 664,691, 671,203 idi. Protein karbonil düzeyleri 26,799, 40,30, 33,052, 34,579 ve 32,79 olarak ölçüldü. Son olarak MDA düzeyleri ise 5,239, 9,814, 6,695, 5,771 ve 5,836 olarak bulundu. Kısaca; POM ve TAN, antioksidan fonksiyonlarını malondialdehit (MDA) ve protein karbonil düzeylerini düşürerek ve süperoksit dismutaz (SOD) ve katalaz (CAT) aktivitesini artırarak gösterdiler. Ayrıca bu ajanlar anti-inflamatuar etkilerini TNF-α, IL-6 ve IL-1β düzeylerini azaltarak ve IL-10 düzeylerini yükselterek sergilemişlerdir.
Sonuç: Tangeretin ve pomegrenatın etanol kaynaklı akut gastrik ülserine karşı potansiyel bir gastroprotektif etkiye sahip olduğu ve kombine tedavinin tek başına POM veya TAN'ın etkisinden daha faydalı olduğunu göstermektedir. Ayrıca bu etkinin, seçilen her iki flavonoidin sinerjistik etki göstererek inflamasyon parametrelerinin düzeylerini azaltabilmesi ve antioksidan düzeylerini yükseltebilmesinden kaynaklandığı düşünülmektedir.

Keywords

Mide ülseri, pomegranate, tangeretin, etanol, rat

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

Abstract

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.

Keywords

Gastric ulcer, pomegranate, tangeretin, ethanol; rat

References

• Xie X, Ren K, Zhou Z, Dang C, Zhang H. The global, regional and national burden of peptic ulcer disease from 1990 to 2019: a population-based study. BMC Gastroenterol. 2022;22:58.
• Omar H, Nordin N, Hassandarvish P, Hajrezaie M, Azizan AHS, Fadaeinasab M et al. Methanol leaf extract of actinodaphne sesquipedalis (lauraceae) enhances gastric defense against ethanol-induced ulcer in rats. Drug Des Devel Ther. 2017;11:1353-1365.
• Aleid IS, Alfheeaid HA, Aljutaily T, Alhomaid RM, Alharbi HF, Althwab SA 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. nutrients. 2021;13:3499.
• Oueslati S, Serairi Beji R, Zar Kalai F, Soufiani M, Zorrig W, Aissam S et al. Antioxidant potentialities and gastroprotective effect of reichardia picroides extracts on Ethanol/HCl induced gastric ulcer rats. Int J Environ Health Res. 2023:1-12.
• Aziz RS, Siddiqua A, Shahzad M, Shabbir A, Naseem N. 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. Biomed Pharmacother. 2019;110:554-560.
• Ciciliato MP, de Souza MC, Tarran CM, de Castilho ALT, Vieira AJ, Rozza AL. Anti-inflammatory effect of vanillin protects the stomach against ulcer formation. Pharmaceutics. 2022;14:755.
• İlhan N, Susam S, Gül HF, İlhan N. The therapeutic effects of thalidomide and etanercept on septic rats exposed to lipopolysaccharide. Ulus Travma Acil Cerrahi Derg. 2019;25:99-104.
• Abd el-Rady NM, Dahpy MA, Ahmed A, Elgamal DA, Hadiya S, Ahmed MA 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. Front Physiol. 2021;12:649462.
• Thangaraj K, Natesan K, Palani M, Vaiyapuri M. Orientin, a flavanoid, mitigates 1, 2 dimethylhydrazine-induced colorectal lesions in Wistar rats fed a high-fat diet. Toxicol Rep. 2018;5:977-987.
• Zaghlool SS, Abo-Seif AA, Rabeh MA, Abdelmohsen UR, Messiha BA. Gastro-protective and anti-oxidant potential of althaea officinalis and solanum nigrum on pyloric ligation/indomethacin-induced ulceration in rats. Antioxidants. 2019;8:512.
• Arafa E-SA, Shurrab NT, Buabeid MA. Therapeutic implications of a polymethoxylated flavone, tangeretin, in the management of cancer via modulation of different molecular pathways. Adv Pharmacol Pharm Sci. 2021;2021:4709818.
• Rafiq S, Kaul R, Sofi S, Bashir N, Nazir F, Nayik GA. Citrus peel as a source of functional ingredient: a review. J Saudi Soc Agric Sci. 2018;17:351-58.
• Hung W-L, Chang W-S, Lu W-C, Wei G-J, Wang Y, Ho C-T et al. Pharmacokinetics, bioavailability, tissue distribution and excretion of tangeretin in rat. J Food Drug Anal. 2018;26:849-57.
• Wang M, Meng D, Zhang P, Wang X, Du G, Brennan C et al. Antioxidant protection of nobiletin, 5-demethylnobiletin, tangeretin, and 5-demethyltangeretin from citrus peel in Saccharomyces cerevisiae. J Agric Food Chem. 2018;66:3155-60.
• Yumnam S, Raha S, Kim SM, Venkatarame Gowda Saralamma V, Lee HJ, Ha SE et al. Identification of a novel biomarker in tangeretin‑induced cell death in AGS human gastric cancer cells. Oncol Rep. 2018;40:3249-60.
• Chou Y-C, Ho C-T, Pan M-H. Immature Citrus reticulata extract promotes browning of beige adipocytes in high-fat diet-induced C57BL/6 mice. J Agric Food Chem. 2018;66:9697-9703.
• Ijaz MU, Shahab MS, Samad A, Ashraf A, Al-Ghanim K, Mruthinti SS et al. Tangeretin ameliorates bisphenol induced hepatocyte injury by inhibiting inflammation and oxidative stress. Saudi J Biol Sci. 2022;29:1375-79.
• Nazari Soltan Ahmad S, Rashtchizadeh N, Argani H, Roshangar L, Ghorbanihaghjo A, Sanajou D et al. Tangeretin protects renal tubular epithelial cells against experimental cisplatin toxicity. Iran J Basic Med Sci. 2019;22:179-86.
• Budiene J, Guclu G, Oussou KF, Kelebek H, Selli S. Elucidation of volatiles, anthocyanins, antioxidant and sensory properties of cv. caner pomegranate (Punica granatum L.) juices produced from three juice extraction methods. Foods. 2021;10:1497.
• Bagheri S, Khorramabadi RM, Assadollahi V, Khosravi P, Cheraghi Venol A, Veiskerami S et al. The effects of pomegranate peel extract on the gene expressions of antioxidant enzymes in a rat model of alloxan-induced diabetes. Arch Physiol Biochem. 2023;129:870-8.
• Cano-Lamadrid M, Lech K, Michalska A, Wasilewska M, Figiel A, Wojdyło A 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. Food Chem. 2017;232:306-15.
• Lebda MA, El-Far AH, Noreldin AE, Elewa YH, Al Jaouni SK, Mousa SA. Protective effects of miswak (salvadora persica) against experimentally induced gastric ulcers in rats. Oxid Med Cell Longev. 2018;2018:6703296.
• Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin phenol reagent. J Biol Chem. 1951;193:265-75.
• Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34:497-500.
• Aebi H. Catalase in vitro. Methods Enzymol. 1984;105:121-26.
• Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG et al. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol. 1990;186:464-78.
• Arslan AK, Yaşar Ş, Çolak C, Yoloğlu S. WSSPAS: an interactive web application for sample size and power analysis with R using shiny. Turkiye Klinikleri J Biostat. 2018;10:224-46.
• Mousa AM, El-Sammad NM, Hassan SK, Madboli AENA, Hashim AN, Moustafa ES et al. Antiulcerogenic effect of cuphea ignea extract against ethanol-induced gastric ulcer in rats. BMC Complement Altern Med. 2019;19:345.
• Kangwan N, Park J-M, Kim E-H, Hahm KB. Quality of healing of gastric ulcers: natural products beyond acid suppression. World J Gastrointest Pathophysiol. 2014;5:40-7.
• Kaeidi A, Sahamsizadeh A, Allahtavakoli M, Fatemi I, Rahmani M, Hakimizadeh E et al. The effect of oleuropein on unilateral ureteral obstruction induced-kidney injury in rats: the role of oxidative stress, inflammation and apoptosis. Mol Biol Rep. 2020;47:1371-79.
• Kaeidi A, Taghipour Z, Allahtavakoli M, Fatemi I, Hakimizadeh E, Hassanshahi J. Ameliorating effect of troxerutin in unilateral ureteral obstruction induced renal oxidative stress, inflammation, and apoptosis in male rats. Naunyn Schmiedebergs Arch Pharmacol. 2020;393:879-88.
• Ercan G, Tartar RI, Solmaz A, Gulcicek OB, Karagulle OO, Meric S et al. Potent therapeutic effects of ruscogenin on gastric ulcer established by acetic acid. Asian J Surg. 2020;43:405-16.
• El-Sisi AE, Sokar SS, Abu-Risha SE, Khira DY. The potential beneficial effects of sildenafil and diosmin in experimentally-induced gastric ulcer in rats. Heliyon. 2020;6:e04761.
• Yang H, Lu Y, Zeng X-F, Li L, Zhang R-P, Ren Z-K et al. Antichronic gastric ulcer effect of zinc-baicalin complex on the acetic acid-induced chronic gastric ulcer rat model. Gastroenterol Res Pract. 2018;2018:1275486.
• Tamaddonfard E, Erfanparast A, Farshid AA, Imani M, Mirzakhani N, Salighedar R et al. Safranal, a constituent of saffron, exerts gastro-protective effects against indomethacin-induced gastric ulcer. Life Sci. 2019;224:88-94.
• Eraslan E, Tanyeli A, Güler MC, Kurt N, Yetim Z. Agomelatine prevents indomethacin-induced gastric ulcer in rats. Pharmacol Rep. 2020;72:984-91.
• Akanda MR, Kim I-S, Ahn D, Tae H-J, Nam H-H, Choo B-K et al. Anti-inflammatory and gastroprotective roles of rabdosia inflexa through downregulation of pro-inflammatory cytokines and MAPK/NF-κB signaling pathways. Int J Mol Sci. 2018;19:584.
• Li W-F, Hao D-J, Fan T, Huang H-M, Yao H, Niu X-F. Protective effect of chelerythrine against ethanol-induced gastric ulcer in mice. Chem Biol Interact. 2014;208:18-27.
• Wang R, Sun F, Ren C, Zhai L, Xiong R, Yang Y et al. Hunan insect tea polyphenols provide protection against gastric injury induced by HCl/ethanol through an antioxidant mechanism in mice. Food Funct. 2021;12:747-60.
• Gong G, Zhao R, Zhu Y, Yu J, Wei B, Xu Y et al. Gastroprotective effect of cirsilineol against hydrochloric acid/ethanol-induced gastric ulcer in rats. Korean J Physiol Pharmacol. 2021;25:403-11.
• Ilhan N, Bektas I, Susam S, Ozercan IH. Protective effects of rosmarinic acid against azoxymethane‐induced colorectal cancer in rats. J Biochem Mol Toxicol. 2022;36:e22961.
• El-Ashmawy NE, Khedr EG, El-Bahrawy HA, Selim HM. Nebivolol prevents indomethacin-induced gastric ulcer in rats. J Immunotoxicol. 2016;13:580-9.
• Cambay Z, Ilhan N, Susam S, Muz MH. BMI and adipocytokine changes in COPD exacerbation and stable COPD. Indian J Biochem Biophys. 2021;58:472-77.
• Duran Y, Karaboğa İ, Polat FR, Polat E, Erboğa ZF, Ovalı MA et al. Royal jelly attenuates gastric mucosal injury in a rat ethanol-induced gastric injury model. Mol Biol Rep. 2020;47:8867-79.
• Matsui H, Shimokawa O, Kaneko T, Nagano Y, Rai K, Hyodo I. The pathophysiology of non-steroidal anti-inflammatory drug (NSAID)-induced mucosal injuries in stomach and small intestine. J Clin Biochem Nutr. 2011;48:107-111.
• Amirshahrokhi K, Khalili A-R. Methylsulfonylmethane is effective against gastric mucosal injury. Eur J Med Chem Rep. 2017;811:240-48.
• Ahmed I, Elkablawy M, El-Agamy D, Bazarbay A, Ahmed N. Carvedilol safeguards against aspirin-induced gastric damage in rats. Hum Exp Toxicol. 2020;39:1257-67.
• Çıkım G, Günal MY, Abdullah T, Kilinc M, Hansu K, Susam S. In twin pregnancies, zinc and iron decreased, while copper increased minimally. Mid Blac Sea J Health Sci. 2022;8:450-57.
• Fujii J, Homma T, Osaki T. Superoxide radicals in the execution of cell death. Antioxidants. 2022;11:501.
• Ighodaro O, Akinloye O. First line defence antioxidants-superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPX): their fundamental role in the entire antioxidant defence grid. Alexandria J Med. 2018;54:287-93.
• Liu J, Lin H, Yuan L, Wang D, Wang C, Sun J et al. Protective effects of anwulignan against HCl/ethanol-induced acute gastric ulcer in mice. Evid Based Complement Alternat Med. 2021;2021:9998982.