Bir Tavşan Steatohepatit Modelinde Narın (Punica Granatum L.) Hepatoprotektif Etkisi

Year 2021, Volume: 14 Issue: 4, 507 - 519, 31.12.2021

Durmuş Fatih Başer Esra Küpeli Akkol Mehmet Bozkurt İpek Süntar Turan Civelek

https://doi.org/10.30607/kvj.991650

Abstract

Bu çalışmada, bir steatohepatit tavşan modelinde Liyofilize nar suyu ekstresinin (LPJE) karaciğer koruması, aktivitesi ve olası yan etkilerinin gösterilmesi amaçlandı ve 48 tavşan kullanıldı. Birinci grup (Grup 1) tavşanlara standart bir diyet (SD), ikinci grup (Grup 2) tavşanlara ise yüksek yağlı bir diyet (HFD) verildi. Her iki gruptaki üçer alt grup tavşanlara sekiz hafta boyunca eş zamanlı olarak üç farklı dozda LPJE (25 mg/kg, 50 mg/kg ve 100 mg/kg) verildi. Pozitif ve standart kontrol grubu tavşanlara ise 1 ml cmc solüsyonu içirildi. Sonuçlar; serum albümin konsantrasyonunun LPJE grubunda (100 mg/kg) pozitif kontrol grubundan önemli ölçüde farklı olduğunu gösterdi. En düşük kolesterol konsantrasyonu, Grup 2'nin (96.71 ± 12.03) LPJE (50mg/kg) uygulanan alt grubunda bulundu. Histopatolojik inceleme sonuçlarına göre Grup 2 istatistiksel olarak farklılık göstermedi; ancak en düşük karaciğer yağlanma derecesi LPJE (50 mg/kg) alt grubunda %26.49 ± 8.64 olarak ölçüldü. Sonuç olarak, liyofilize nar ekstresinin hepatoprotektif aktivite gösterdiği ve alkolsüz steatohepatit (NASH) tavşan modelinde en etkili dozun 50 mg/kg olduğu saptandı. Ayrıca tavşanlarda 100 mg/kg nar suyu ekstresine kadar herhangi bir yan etki tespit edilmedi.

Keywords

Punica granatum, antioksidan aktivite, biyoaktivite, alkolsüz steatohepatit

Supporting Institution

Afyon Kocatepe Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi

Hepatoprotective Effect of Pomegranate (Punica Granatum L.) in A Rabbit Model of Steatohepatitis

Abstract

The study aimed to exhibit liver protection, activity, and probable side effects of LPJE on a steatohepatitis rabbit model. In this study, 48 rabbits were used. The first group (Group 1) rabbits were fed a standard diet (SD), while the second group (Group 2) rabbits were fed a high-fat diet (HFD). In two groups, three different doses of LPJE (25 mg/kg, 50 mg/kg, and 100 mg/kg) were given simultaneously to the rabbits for eight weeks. Results showed that the serum albumin concentration was significantly different in the LPJE group (100 mg/kg) than in the positive control group. The cholesterol concentration of the LPJE (50mg/kg) administered subgroup of Group 2 (96.71 ± 12.03) was found to be the lowest. According to histopathological examination results, Group 2 did not display a statistical difference; however, the lowest liver fat deposition degree was 26.49 ± 8.64% in the LPJE (50 mg/kg) subgroup. As a result of this study, the lyophilized pomegranate extract has hepatoprotective activity. The most effective dose was 50 mg/kg on the non-alcoholic steatohepatitis (NASH) rabbit model. No side effects were determined up to 100 mg/kg pomegranate juice extract on rabbits.

Keywords

: Punica granatum, antioxidant activity, bioactivity, non-alcoholic steatohepatitis

References

• Adorini L, Pruzanski M, Shapiro D. Farnesoid X receptor targeting to treat nonalcoholic steatohepatitis. Drug Discovery Today. 2012; 17(17-18):988-997.
• Afaq F, Saleem M, Krueger CG, Reed JD, Mukhtar H. Anthocyanin and hydrolysable tannin-rich pomegranate fruit extract modulates MAPK and NF-ĸB pathways and inhibits skin tumorigenesis in CD-1 mice. International Journal of Cancer. 2005; 113(3):423-433.
• Angulo P, Keach JC, Batts KP, Lindor KD. Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology. 1999; 30(6):1356-1362.
• Ashoush IS, El-Batawy OI, El-Shourbagy GA. Antioxidant activity and hepatoprotective effect of pomegranate peel and whey powders in rats. Annals of Agricultural Sciences. 2013; 58(1):27-32.
• Aviram M, Dornfeld L, Rosenblat M, Volkova N, Kaplan M, Coleman R, Hayek T, Presser D, Fuhrman B. Pomegranate juice consumption reduces oxidative stress, atherogenic modifications of LDL, and platelet aggregation: studies in humans and in atherosclerotic apolipoprotein E-deficient mice. The American Journal of Clinical Nutrition. 2000; 71(5):1062–1076.
• Bayan K, Danış R, Altıntas A, Keklikçi SU. Nonalkolik Hepatosteatozun Biyokimyasal Özellikleri. Dicle Tıp Dergisi. 2004; 31(1):23-26.
• Besson-Bard A, Pugin A, Wendehenne D. New insights into nicric oxide signaling in plants. Annual Review of Plant Biology. 2008; 59:21-39.
• Brunt EM. Pathology of steatohepatitis. Best Practice & Research Clinical Gastroenterology. 2002; 16(5):691-707.
• Celik I, Temur A, Isik I. Hepatoprotective role and antioxidant capacity of pomegranate (Punica granatum) flower infusion against trichlorocetic acid-exposed in rats. Food and Chemical Toxicology. 2009; 47(1):145-149.
• Civelek T, Aydin I, Cingi CC, Yilmaz O, Kabu M. Serum Non-Esterified Fatty Acids and Beta-Hydroxybutyrate in Dairy Cows with Retained Placenta. Pakistan Veterinary Journal. 2011; 31(4):341-344.
• Çolak Y, Tuncer İ. Nonalkolik karaciğer yağlanması ve steatohepatit. İstanbul Tıp Fakültesi Dergisi. 2010; 73(3):85-88.
• El-Nemr SE, Ismail IA, Ragab M. Chemical composition of juice and seeds of pomegranate fruit. Food/Nahrung. 1990; 34(7):601-606.
• Esmaillzadeh A, Tahbaz F, Gaieni I, Alavi-Majd H, Azadbakht L. Cholesterol-lowering effect of concentrated pomegranate juice consumption in type II diabetic patients with hyperlipidemia. International Journal for Vitamin and Nutrition Research. 2006; 76(3):147-51.
• Faria A, Monteiro R, Mateus N, Azevedo I, Calhau C. Effect of pomegranate (Punica granatum) juice intake on hepatic oxidative stress. European Journal of Nutrition. 2007; 46(5):271-278.
• Fuhrman B, Volkova N, Aviram M. Pomegranate juice inhibits oxidized LDL uptake and cholesterol biosynthesis in macrophages. The Journal of Nutritional Biochemistry. 2005; 16(9):570-576.
• Gonzalez-Ortiz M, Martinez-Abundis E, Espinel-Bermudez MC, Perez-Rubio KG.. Effect of pomegranate juice on insulin secretion and sensitivity in patient with obesity. Annals of Nutrition and Metabolism. 2011; 58(3):220-223.
• Gören B, Fen T. Non-Alkolik yağlı karaciğer hastalığı [Non-alcoholic fatty liver disease: review]. Türkiye Klinikleri Tıp Bilimleri Dergisi. 2005; 25(6):841-850.
• Gurib-Fakim A. Medicinal plants: Traditions of yesterday and drugs of tomorrow. Molecular Aspects of Medicine. 2006; 27(1):1-93.
• Haber D, Seeram NP, Wyatt H, Henning SM, Zhang Y, Ogden LG, Dreher M, Hill JO. Safety and antioxidant activity of a pomegranate ellagitannin-enriched polyphenol dietary supplement in owerweight individuals with increased waist size. Journal of Agricultural and Food Chemistry. 2007; 55(24):10050-10054.
• Hancock CR, Han D, Chen M, Terada S, Toshihiro Y, David C, Holloszy JO. High-fat diets cause insulin resistance despite an increase in muscle mitochondria. Prooceedings of the National Academy of Sciences of the United States of America. 2008; 105(22):7815-7820.
• Hontecillas R, O’Shea M, Einerhand A, Diguardo M, Riera JB. Activation of PPAR gamma and alpha by unicic aid ameliorates glucose tolerance and suppresses obesity-related inflammation. Journal of the American College of Nutrition. 2009; 28(2):184-195.
• Hosseini B, Saedisomeolia A, Wood LG, Yaseri M, Tavasoli S. Effects of pomegranate extract supplementation on inflammation in overweight and obese individuals: a randomized controlled clinical trial. Complementary Therapies in Clinical Practice. 2016; 22:44-50.
• Huang TH, Peng G, Kota BP, Li GQ, Yamahara J, Roufogalis BD, Li Y. Pomegranate flower improves cardiac lipid metabolism in a diabetic rat model: role of lowering circulating lipids. British Journal of Pharmacology. 2005b; 145(6):767–774.
• Huang TH, Peng G, Kota BP, Li GQ. Yamahara J, Roufogalis BD, Li Y. Anti-diabetic action of Punica granatum flower extract:activation of PPAR-gamma and identification of an active component. Toxicology and Applied Pharmacology. 2005a; 207(2): 160–169.
• Ideo G, Morhanti A, Dioguardi N. Gamma-glutamyl transpeptidase: a clinical and experimental study. Digestion. 1972; 5(6):326-336.
• Jelodar G, Mohsen M, Shahram S. Effect of walnut leaf, coriander and pomegranate on blood glucose and histopathology of pancreas of alloxan induced diabetic rats. African Journal of Traditional, Complementary and Alternative Medicines. 2007; 4(3):299–305.
• Kaur G, Jabbar Z, Athar M, Alam MS. Punica granatum (pomegranate) flower extract possesses potent antioxidant activity and abrogates Fe-NTA induced hepatotoxicity in mice. Food and Chemical Toxicology. 2006; 44(7):984-993.
• Kaysen GA. Biological basis of hypoalbuminemia in ESRD. Journal of the American Society of Nephrology. 1998; 9(12):2368-2376.
• Lei F, Zhang XN, Wang W, Xing DM, Xie WD, Su H, Du LJ. Evidence of anti-obesity effects of the pomegranate leaf extract in high-fat diet induced obese mice. International Journal of Obesity. 2007; 31(6):1023-1029.
• Lillie RD, Ashburn LL. Supersaturated solutions of fat stains in dilute isopropanol for demonstration of acute fatty degeneration not shown by Herxheimer’s technique. Archives of Pathology & Laboratory Medicine. 1943; 36:432.
• Ludwig J, Viggiano TR, Mcgill DB. Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clinic Proceedings. 1980; 55(7):434-438.
• Mamurekli E, Dinç G, Özcan C. İzmir egekent sağlık ocağı polikliniği'ne başvuran hastalarda Hiperkolesterolemi sıklığı ve hiperkolesterolemi ile ilişkili risk faktörleri. Ege Tıp Dergisi. 2000; 39(3):181-186.
• Marchesini G, Marzocchi R. Metabolic syndrome and NASH. Clinics in Liver Disease. 2007; 11(1):1051-117
• Moneim AEA. Antioxidant activities of Punica granatum (pomegranate) peel extract on brain of rats. Journal of Medicinal Plants Research. 2012; 6(2):195-199.
• Neuschwander-Tetri BA. Nonalcoholic steatohepatitis and the metabolic syndrome. The American Journal of the Medical Sciences. 2005; 330(6):326-335.
• Ogawa T, Fujii H, Yoshizato K, Kawada N. A human-type nonalcoholic steatohepatitis model with advanced fibrosis in rabbits. The American Journal of Pathology. 2010; 177(1):153-165.
• Osman M, Ahmed M, Mahfouz S, Elaby S. Biochemical studies on hepatoprotective effects of pomegranate and guava ethanol extracts. New York Science Journal. 2011; 4(3):27-41.
• Pagano G, Pacini G, Musso G, Gambino R, Mecca F, Depetris N, Cassader M, David E, Cavallo-Perin P, Rizzetto M. Nonalcoholic steatohepatitis, insulin resistance and metabolic syndrome: further evidence for an etiologic association. Hepatology. 2002; 35(2):367-372.
• Parmar HS, Kar A. Medicinal values of fruit peels from Citrus sinensis, Punica granatum, and Musa paradisiaca with respectto alterations in tissue lipid peroxidation and serum concentration of glucose, insulin, and thyroid hormones. Journal of Medicinal Food. 2008; 11(2):376-381.
• Patel C, Dadhaniya P, Hingorani L, Soni MG. Safety assessment of pomegranate fruit extract: acute and subchronic toxicity studies. Food and Chemical Toxicology. 2008; 46(8):2728-2735.
• Pfohl M, DaSilva NA, Marques E, Agudelo J, Liu C, Goedken M, Slitt AL, Seeram NP, Ma H. Hepatoprotective and anti-inflammatory effects of a standardized pomegranate (Punica granatum) fruit extract in high fat diet-induced obese C57BL/6 mice. International Journal of Food Sciences and Nutrition. 2020 https://doi.org/10.1080/09637486.2020.1849041.
• Rashidi AA, Menshadi FJ, Zinsaz A, Sadafi Z. Effect of concentrated pomegranate juice consmption on glucose and lidip profile concentration in type 2 diabetic patient. Zahedan Journal of Research in Medical Sciences. 2013; 15(6):40-42.
• Rock W, Rosenblat M, Miller-Lotan R, Levy AP, Elias M, Aviram M. Consumption of wonderful variety pomegranate juice and extract by diabetic patientsincreases paraoxonase 1 association with high-density lipoprotein and stimulates its catalytic activities. Journal of Agricultural and Food Chemistry. 2008; 56(18):8704–8713.
• Scarpini E, Scheltens P, Feldman H. Treatment of Alzheimer’s disease: current status and new perspectives. The Lancet Neurology. 2003; 2(9):539-547.
• Shaban NZ, El-Kersh ML, El-Rashidy FH, Habashy NH. Protective role of Punica granatum (pomegranate) peel and seed oil extracts on diethylnitrosamine and phenobarbital-induced hepatic injury in male rats. Food Chemistry. 2013; 141(3):1587-1596.
• Sonsuz A, Baysal B. Karaciğer yağlanması ve non alkolik steatohepatit. Güncel Gastroenteroloji. 2011; 15(2):98-106.
• Squilacci G, Di Maggio G. Acute morbidity and mortality from decoctions of bark of Punica granatum. Bollettino Societa Italiana Biologia Sperimentale. 1946; 1095-1096.
• Sumner MD, Elliott-Eller M, Weidner G, Daubenmier JJ, Chew MH, Marlin R, Raisin CJ, Ornish D. Effects of pomegranate juice consumption on myocardial perfusion in patients with coronary heart diseases. American Journal of Cardiology. 2005; 96(6):810-814.
• Takahashi Y, Sugimoto K, Inui H, Fukusato T. Current pharmacological therapies for nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. World Journal of Gastroenterology. 2015; 21(13):3777–3785.
• Türk G, Sönmez M, Aydin M, Yüce A, Gür S, Yüksel M, Aksu EH, Aksoy H. Effects of pomegranate juice consumption on sperm quality, spermatogenic cell density, antioxidant activity and testosterone level in male rats. Clinical Nutrition. 2008; 27(2):289-296.
• Vidal A, Fallarero A, Pena BR, Medina ME, Gra B, Rivera F, Gutierrez Y, Vuorela PM. Studies on the toxicity Punica granatum L. (Punicaceae) whole fruit extracts. Journal of Ethnopharmacology. 2003; 89(2-3):295-300.
• Vroegrijk IO, Van Diepen JA, Van Den Berg S, Westbroek I, Keizer H, Gambelli L, Hontecillas R, Bassaganya-Riera J, Zondag GC, Romijn JA, Havekes LM, Voshol PJ. Pomegranate seed oil, a rich source of punicic acid, prevents diet-induced obesity and insulin resistance in mice. .2011; 49(6):1426-1430.
• Xu KZ, Zhu C, Kim MS, Yamahara J, Li Y.Pomegranate flower ameliorates fatty liver in an animal model of type 2 diabetes and obesity. Journal of Ethnopharmacology. 2009; 123(2):280–287.
• Yüce A, Aksakal M. Ratların karaciğer ve testis dokusundaki antioksidan aktivite üzerine nar suyunun etkisi. Fırat Üniversitesi Sağlık Bilimleri Dergisi. 2007; 21(6):253-256.
• Zhang L, Gao Y, Zhang Y, Liu J, Yu J. Changes in bioactive compounds and antioxidant activities in pomegranate leaves. Scientia Horticulturae. 2010; 123(4):543–546.
• Zou X, Yan C, Shi Y, Cao K, Xu J, Wang X, Chen C, Luo C, Li Y, Gao J, Pang W, Zhao J, Zhao F, Li H, Zheng A, Sun W, Long J, Szeto IM, Zhao Y, Feng Z.Mitochondrial dysfunction in obesity-associated nonalcoholic fatty liver disease: the protective effects of pomegranate with its active component punicalagin. .2014; 21(11):1557-1570.