Hypoglycemic and Hypolipidemic Effects of Ethanolic Extract of Pomegranate Peels, Rinds, and Seeds in Alloxan-Induced Diabetic Rats

http://www.doi.org/10.26538/tjnpr/v7i8.40

Authors

  • Khalid M. Alqaisi Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan.
  • Talal S. Al-Qaisi Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan.
  • Husni S. Farah Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan.
  • Thamer A. Hamda Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan.
  • Khaled A. Ahmed Department of Medical Laboratory Sciences, Faculty of Allied Medical Sciences, Al-Ahliyya Amman University, Amman 19328, Jordan.
  • Elsayed Elbadrawy Mansoura University, Faculty of Specific Education, Department of Nutrition, Mansoura City 35516, Egypt

Keywords:

Very-low-density lipoprotein, High-density lipoprotein, Low-density lipoprotein, Triglyceride, Cholesterol, Diabetes, Ethanol extract, Pomegranates

Abstract

Pomegranates are one of the fruits that are most frequently consumed in the Middle East and have a medical effect. This study aimed to examine the antidiabetic and antilipidemic effect of pomegranate fruit parts including peels, seeds, and rinds extracted using ethanol on the blood glucose, cholesterol, triglyceride, low-density lipoprotein (LDL), high-density lipoprotein (HDL), and very-low-density lipoprotein (VLDL). Control (non-treated) rats and alloxan-diabeticinduced rats were used in this study. The alloxan-diabetic-induced rats were divided into four groups and each group received a subcutaneously injected either peels, seeds, or grind ethanol
extract, and a group was treated with the drug glipizide for 28 days. Data showed a significant effect for the pomegranate peels and rind ethanol extract in lowering glucose levels (P = 0.0295) with no significant effect for the juice extract on blood glucose levels. Cholesterol, triglycerides, LDL, and VLDL were all significantly reduced by the pomegranate fruit component extracts employed in this study (P = 0.014). However, no significant effect was observed for any extract on the HDL levels in the blood (P > 0.5). In conclusion, the rind of the pomegranate can be used in optimizing blood lipid profile and glucose, in addition to seeds and peels. 

References

Isah T. Stress and defense responses in plant secondary metabolites production. Biol Res. 2019; 52.

Yang L, Wen KS, Ruan X, Zhao YX, Wei F, Wang Q. Response of plant secondary metabolites to environmental factors. Molecules. 2018; 23(4):762.

Barbulova A, Colucci G, Apone F. New trends in cosmetics: By-products of plant origin and their potential use as cosmetic active ingredients. Cosmetics. 2015; 2(2):82-92.

Atanasov AG, Waltenberger B, Pferschy-Wenzig EM, Linder T, Wawrosch C, Uhrin P, Temml V, Wang L, Schwaiger S, Heiss EH, Rollinger JM. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol Adv. 2015; 33(8):1582-614.

Mazid M, Khan TA, Mohammad F. Role of secondary metabolites in defense mechanisms of plants. Biol Med. 2011; 3(2):232-49.

Li GQ, Kam A, Wong KH, Zhou X, Omar EA, Alqahtani A, Li KM, Razmovski-Naumovski V, Chan K. Herbal medicines for the management of diabetes. Diabetes: An Old Disease, a New Insight. 2013; 396-413.

Alam S, Dhar A, Hasan M, Richi FT, Emon NU, Aziz MA, Mamun AA, Chowdhury MNR, Hossain MJ, Kim JK, Kim B, Hasib MS, Zihad SMNK, Haque MR, Mohamed IN, Rashid MA. Antidiabetic Potential of Commonly Available Fruit Plants in Bangladesh: Updates on Prospective

Phytochemicals and Their Reported MoAs. Molecules. 2022; 27(24):8709.

Egharevba E, Chukwuemeke-Nwani P, Eboh U, Okoye E, Bolanle I O, Oseghale I O, Imieje VO, Erharuyi O, Falodun A. Evaluation of the antioxidant and hypoglycaemic potentials of the leaf extracts of Stachytarphyta jamaicensis (Verbenaceae). Trop J Nat Prod Res. 2019;

(5):170-174.

Reddy MK, Gupta SK, Jacob MR, Khan SI, Ferreira D. Antioxidant, antimalarial and antimicrobial activities of tannin-rich fractions, ellagitannins and phenolic acids from Punica granatum L. Planta Med. 2007; 53(05):461-7.

Serreli G, Deiana M. In vivo formed metabolites of polyphenols and their biological efficacy. Food Funct. 2019; 10(11):6999-7021.

Niedzwiecki A, Roomi MW, Kalinovsky T, Rath M. Anticancer efficacy of polyphenols and their combinations. Nutrients. 2016; 8(9):552.

Chaabna N, Naili O, Ziane N, Bensouici C, Dahamna S, Harzallah D. In vitro Antioxidant, anti-Alzheimer and Antibacterial Activities of Ethyl acetate and n-Butanol Fractions of Punica granatum Peel from Algeria. Trop J Nat Prod Res. 7(7):3470–3477. Doi.org/10.26538/tjnpr/v7i7.27

Akhtar S, Ismail T, Fraternale D, Sestili P. Pomegranate peel and peel extracts: Chemistry and food features. Food Chem. 2015; 174:417-25.

Viuda‐Martos M, Fernández‐López J, Pérez‐Álvarez JA. Pomegranate and its many functional components as related to human health: a review. Compr Rev Food Sci Food Safety. 2010; 9(6):635-54.

Moradi MT, Karimi A, Shahrani M, Hashemi L, GhaffariGoosheh MS. Anti-influenza virus activity and phenolic content of pomegranate (Punica granatum L.) peel extract and fractions. Avicenna J Med Biotechnol. 2019; 11(4):285.

Houston DM, Bugert JJ, Denyer SP, Heard CM. Correction: Potentiated virucidal activity of pomegranate rind extract (PRE) and punicalagin against Herpes simplex virus (HSV) when co-administered with zinc (II) ions, and antiviral activity of PRE against HSV and aciclovir-resistant HSV. Plos One. 2017; 12(11):e0188609.

Howell AB, D'Souza DH. The pomegranate: effects on bacteria and viruses that influence human health. EvidenceBased Complement Altern Med. 2013; 2013: 606212. Doi: 10.1155/2013/606212.

Yan-Ling Z, Dong-Qing Z, Chang-Quan H, Bi-Rong D. Cigarette smoking and its association with serum lipid/lipoprotein among Chinese

nonagenarians/centenarians. Lipids Health Dis. 2012; 11(1):1-6.

Toth PP. Subclinical atherosclerosis: what it is, what it means and what we can do about it. Int J Clin Pract. 2008; 62(8):1246-54.

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. Int J Obes. 2007; 31(6):1023-9.

Al-Muammar MN, Khan F. Obesity: the preventive role of the pomegranate (Punica granatum). Nutrition. 2012; 28(6):595-604.

Sadeghipour A, Eidi M, Ilchizadeh Kavgani A, Ghahramani R, Shahabzadeh S, Anissian A. Lipid lowering effect of Punica granatum L. peel in high lipid diet fed male rats. Evidence-Based Complement Altern Med. 2014; 2014.

Huang TH, Yang Q, Harada M, Li GQ, Yamahara J, Roufogalis BD, Li Y. Pomegranate flower extract diminishes cardiac fibrosis in Zucker diabetic fatty rats: modulation of cardiac endothelin-1 and nuclear factor-kappaB pathways. J Cardiovasc Pharmacol. 2005; 46(6):856-62.

Aviram M, Volkova N, Coleman R, Dreher M, Reddy MK, Ferreira D, Rosenblat M. Pomegranate phenolics from the peels, arils, and flowers are antiatherogenic: studies in vivoin atherosclerotic apolipoprotein E-deficient (E0) mice and in vitro in cultured macrophages and lipoproteins. J Agricul Food Chem. 2008; 56(3):1148-57.

Liu J. Oleanolic acid and ursolic acid: research perspectives. J Ethnopharmacol. 2005; 100(1-2):92-4.

Jang A, Srinivasan P, Lee NY, Song HP, Lee JW, Lee M, Jo C. Comparison of hypolipidemic activity of synthetic gallic acid–linoleic acid ester with mixture of gallic acid and linoleic acid, gallic acid, and linoleic acid on high-fat diet induced obesity in C57BL/6 Cr Slc mice. Chem Biol Interact. 2008; 174(2):109-17.

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. J Ethnopharmacol. 2009; 123(2):280-7.

Virgen-Carrillo CA, Martínez Moreno AG, Valdés Miramontes EH. Potential hypoglycemic effect of pomegranate juice and its mechanism of action: a systematic review. J Med Food. 2020; 23(1):1-1.

Medjakovic S, Jungbauer A. Pomegranate: a fruit that ameliorates metabolic syndrome. Food Funct. 2013; 4(1):19-39.

Les F, Arbonés-Mainar JM, Valero MS, López V. Pomegranate polyphenols and urolithin A inhibit α-glucosidase, dipeptidyl peptidase-4, lipase, triglyceride accumulation and adipogenesis related genes in 3T3-L1 adipocyte-like cells. J Ethnopharmacol. 2018; 220:67-74.

Taheri Rouhi SZ, Sarker M, Rahman M, Rahmat A, Alkahtani SA, Othman F. The effect of pomegranate fresh juice versus pomegranate seed powder on metabolic indices, lipid profile, inflammatory biomarkers, and the histopathology of pancreatic islets of Langerhans in

streptozotocin-nicotinamide induced type 2 diabetic Sprague–Dawley rats. BMC Complement Altern Med. 2017; 17(1):1-3.

Preedy VR, editor. Diabetes: Oxidative stress and dietary antioxidants. Academic Press. 2020.

Grabež M, Škrbić R, Stojiljković MP, Rudić-Grujić V, Paunović M, Arsić A, Petrović S, Vučić V, Mirjanić-Azarić B, Šavikin K, Menković N, Janković T, Vasiljević N. Beneficial effects of pomegranate peel extract on plasma lipid profile, fatty acids levels and blood pressure in patients

with diabetes mellitus type-2: A randomized, double-blind, placebo-controlled study. J Funct Foods. 2020; 64:103692.

Hashemi MS, Namiranian N, Tavahen H, Dehghanpour A, Rad MH, Jam-Ashkezari S, Emtiazy M, Hashempur MH. Efficacy of pomegranate seed powder on glucose and lipid metabolism in patients with type 2 diabetes: a prospective randomized double-blind placebo-controlled clinical trial. Complement Med Res. 2021; 28(3):226-33.

Singh RP, Chidambara Murthy KN, Jayaprakasha GK. Studies on the antioxidant activity of pomegranate (Punica granatum) peel and seed extracts using in vitro models. J Agricul Food Chem. 2002; 50(1):81-6.

Wei XL, Fang RT, Yang YH, Bi XY, Ren GX, Luo AL, Zhao M, Zang WJ. Protective effects of extracts from Pomegranate peels and seeds on liver fibrosis induced by carbon tetrachloride in rats. BMC Complement Altern Med. 2015; 15:1-9.

Stanely P, Prince M, Menon VP. Hypoglycaemic and other related actions of Tinospora cordifolia roots in alloxaninduced diabetic rats. J Ethnopharmacol. 2000; 70(1):9-15.

Szabadfi K, Pinter E, Reglodi D, Gabriel R. Neuropeptides, trophic factors, and other substances providing morphofunctional and metabolic protection in experimental models of diabetic retinopathy. Int Rev Cell Mol Biol. 2014; 311:1-21.

Schelleman H, Bilker WB, Brensinger CM, Wan F, Hennessy S. Anti‐infectives and the risk of severe hypoglycemia in users of glipizide or glyburide. Clin Pharmacol & Ther. 2010; 88(2):214-22.

Groop L, Groop PH, Stenman S, Saloranta C, Tötterman KJ, Fyhrquist F, Melander A. Comparison of pharmacokinetics, metabolic effects and mechanisms of action of glyburide and glipizide during long-term treatment. Diabetes Care. 1987; 10(6):671-8.

Jandal MM, Naji EZ. Study of the effect of Ethanolic extract of pomegranate peels on some blood serum biochemical parameters in alloxan induced diabetes male rats. Tikrit Journal for Agricultural Sciences. 2021; 21(1):138-51.

Taheri Rouhi SZ, Sarker M, Rahman M, Rahmat A, Alkahtani SA, Othman F. The effect of pomegranate fresh juice versus pomegranate seed powder on metabolic indices, lipid profile, inflammatory biomarkers, and the histopathology of pancreatic islets of Langerhans in

streptozotocin-nicotinamide induced type 2 diabetic Sprague–Dawley rats. BMC Complement Altern Med. 2017; 17(1):1-3.

Bergman M, Gidez LI, Eder HA. The effect of glipizide on HDL and HDL subclasses. Diabetes Res (Edinburgh, Scotland). 1986; 3(5):245-8.

Reaven GM. Effect of glipizide treatment on various aspects of glucose, insulin, and lipid metabolism in patients with noninsulin-dependent diabetes mellitus. Am J Med. 1983; 75(5):8-14.

Greenfield MS, Doberne L, Rosenthal M, Vreman HJ, Reaven GM. Lipid metabolism in non-insulin-dependent diabetes mellitus: effect of glipizide therapy. Arch Intern Med. 1982; 142(8):1498-500.

Rudas B. Serum cholesterol levels in alloxan diabetic rats after loading with various alimentary fats. Nature. 1966; 211(5046):320-1.

Sedigheh A, Jamal MS, Mahbubeh S, Somayeh K, Mahmoud RK, Azadeh A, Fatemeh S. Hypoglycaemic and hypolipidemic effects of pumpkin (Cucurbita pepo L.) on alloxan-induced diabetic rats. Afr J Pharm Pharmacol. 2011; 5(23):2620-6.

Bako HY, Mohammad JS, Wazir PM, Bulus T, Gwarzo MY, Zubairu MM. Lipid profile of alloxan-induced diabetic wistar rats treated with methanolic extract of Adansonia digitata fruit pulp. Sci World J. 2014; 9(2):19-24.

El‐Hadary AE, Ramadan MF. Phenolic profiles, antihyperglycemic, antihyperlipidemic, and antioxidant properties of pomegranate (Punica granatum) peel extract. J Food Biochem. 2019; 43(4):e12803.

Rashidi AA, Jafari-Menshadi F, Zinsaz A, Sadafi Z. Effect of concentrated pomegranate juice consumption on glucose and lipid profile concentrations in type 2 diabetic patients. Zahedan J Res Med Sci. 2013; 15(6).

Vattem DA, Shetty K. Biological functionality of ellagic acid: a review. J Food Biochem. 2005; 29(3):234-66.

Bagheri S, Khorramabadi RM, Assadollahi V, Khosravi P, Cheraghi Venol A, Veiskerami S, Ahmadvand H. The effects of pomegranate peel extract on the gene expressions of antioxidant enzymes in a rat model of alloxan-induced diabetes. Arch Physiol Biochem. 2021;1-9.

Sabraoui T, Khider T, Nasser B, Eddoha R, Moujahid A, Benbachir M, Essamadi A. Determination of punicalagins content, metal chelating, and antioxidant properties of edible pomegranate (Punica granatum L) peels and seeds grown in Morocco. Int J Food Sci. 2020; 8885889.

Doi.org/10.1155/2020/8885889

El‐Hadary AE, Ramadan MF. Phenolic profiles, antihyperglycemic, antihyperlipidemic, and antioxidant properties of pomegranate (Punica granatum) peel extract. J Food Biochem. 2019; 43(4):e12803.

Published

2023-08-31

How to Cite

Alqaisi, K. M., Al-Qaisi, T. S., Farah, H. S., Hamda, T. A., Ahmed, K. A., & Elbadrawy, E. (2023). Hypoglycemic and Hypolipidemic Effects of Ethanolic Extract of Pomegranate Peels, Rinds, and Seeds in Alloxan-Induced Diabetic Rats: http://www.doi.org/10.26538/tjnpr/v7i8.40. Tropical Journal of Natural Product Research (TJNPR), 7(8), 3836–3841. Retrieved from https://tjnpr.org/index.php/home/article/view/2463

Most read articles by the same author(s)