Antihyperlipidemic effect of Punica granatum mesocarp extract (PGME) in rats

  • Authors

    • Afaf Afify Benha University
    • Zeinab Hassan Benha University
    • Nehal Abd El-Mageed Benha University
    • Abubakr El-Mahmoudy Benha University
    2022-07-17
    https://doi.org/10.14419/ijpt.v10i1.32086
  • Punica granatum, Mesocarp, Hyperlipidemia, Atherosclerosis, Phytomedicine.
  • Abstract

    Hyperlipidemia is an umbrella term that refers to any disorder of elevated level of lipids circulating in the blood; and is considered the most significant risk factor contributing to the prevalence of cardiovascular, hepatic, and other diseases. The present study was designed to evaluate the possible antihyperlipidemic potential Punica granatum mesocarp extract (PGME) in albino rats using high-fat diet model of hyperlipidemia. Forty-two albino rats were utilized in this experiment arranged randomly in seven groups, six rats each, of different treatments. Hyperlipidemia model was induced by incorporating coconut oil (1.5% w/w) and cholesterol (1.5 % w/w) in diet supplied to rats, for 6 weeks (+ve control); test group rats received PGME at escalating doses of 100 or 200 mg/kg, orally, daily for 6 weeks with keeping on high-fat diet; standard group rats received Rosuvastatin at dose of 2 mg/kg, orally, daily for 6 weeks along with high-fat diet; further 2 groups of rats received only PGME at the same dose levels with keeping on normal diet; while rats of -ve control group received only the vehicles of the used agents. Blood samples were picked out at the end of the experimental course for different assays. Clinicochemical analyses revealed that PGME exhibited dose-dependent protection against hyperlipidemia indicated by improved biomarkers, including, lipid profile parameters, namely cholesterol, triacylglycerols and lipoproteins; enzymatic hepatic parameters, namely, AST, ALT, and GGT; and non-enzymatic parameters, namely, total protein, albumin, globulins, total bilirubin, conjugated bilirubin, unconjugated bilirubin. The mechanism of the obtained lipid profile improvement of PGME may be based on the phytochemical principals Tannins, Phenolics and Flavonoids, indicated by preliminary detection tests. Data of the present study may suggest PGME as a good natural source for promising antihyperlipidemic remedies.

     

     

  • References

    1. [1] Adams J, Abendschein DR, Jaffe AS (1993). Biochemical markers of myocardial injury. Is MB creatine kinase the choice for the 1990s? Circulation 88, 750-763. https://doi.org/10.1161/01.CIR.88.2.750.

      [2] Annegowda H, Nee CW, Mordi M, Ramanathan S, Mansor S (2010). Evaluation of phenolic content and antioxidant property of hydrolysed extracts of Terminalia catappa L. leaf. Asian Journal of Plant Sciences 9, 479. https://doi.org/10.3923/ajps.2010.479.485.

      [3] Aruoma OI (2003). Methodological considerations for characterizing potential antioxidant actions of bioactive components in plant foods. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 523, 9-20. https://doi.org/10.1016/S0027-5107(02)00317-2.

      [4] Aviram M, Volkova N, Coleman R, Dreher M, Reddy MK, Ferreira D, Rosenblat M (2008). Pomegranate phenolics from the peels, arils, and flowers are antiatherogenic: studies in vivo in atherosclerotic apolipoprotein E-deficient (E0) mice and in vitro in cultured macrophages and lipoproteins. Journal of agricultural and food chemistry 56, 1148-1157. https://doi.org/10.1021/jf071811q.

      [5] Bauer JE, Covert SJ (1984). The influence of protein and carbohydrate type on serum and liver lipids and lipoprotein cholesterol in rabbits. Lipids 19, 844-850. https://doi.org/10.1007/BF02534513.

      [6] Bodor GS, Porter S, Landt Y, Ladenson JH (1992). Development of monoclonal antibodies for an assay of cardiac troponin-I and preliminary results in suspected cases of myocardial infarction. Clinical chemistry 38, 2203-2214. https://doi.org/10.1093/clinchem/38.11.2203.

      [7] Bucolo G, David H (1973). Quantitative determination of serum triglycerides by the use of enzymes. Clinical chemistry 19, 476-482. https://doi.org/10.1093/clinchem/19.5.476.

      [8] Burtis CA (1999). Tietz textbook of clinical chemistry: Saunders.

      [9] Chen Y, Krishan M, Nebert DW, Shertzer HG (2012). Glutathione-deficient mice are susceptible to TCDD-Induced hepatocellular toxicity but resistant to steatosis. Chemical research in toxicology 25, 94-100. https://doi.org/10.1021/tx200242a.

      [10] Costamagna MS, Zampini IC, Alberto MR, Cuello S, Torres S, Pérez J, Quispe C, Schmeda-Hirschmann G, Isla MI (2016). Polyphenols rich fraction from Geoffroea decorticans fruits flour affects key enzymes involved in metabolic syndrome, oxidative stress and inflammatory process. Food chemistry 190, 392-402. https://doi.org/10.1016/j.foodchem.2015.05.068.

      [11] Deshpande S, Cheryan M (1987). Determination of phenolic compounds of dry beans using vanillin, redox and precipitation assays. Journal of Food Science 52, 332-334. https://doi.org/10.1111/j.1365-2621.1987.tb06606.x.

      [12] Dong S, Tong X, Liu H, Gao Q (2012). Protective effects of pomegranate polyphenols on cardiac function in rats with myocardial ischemia/reperfusion injury. Nan Fang yi ke da xue xue bao= Journal of Southern Medical University 32, 924-927.

      [13] Drechsler M, Megens RT, van Zandvoort M, Weber C, Soehnlein O (2010). Hyperlipidemia-triggered neutrophilia promotes early atherosclerosis. Circulation 122, 1837-1845. https://doi.org/10.1161/CIRCULATIONAHA.110.961714.

      [14] Ellefson R, Caraway W (1976). Fundamentals of clinical chemistry Ed Tietz NW; p506.

      [15] Fossati P, Prencipe L (1982). Serum triglycerides determined colorimetrically with an enzyme that produces hydrogen peroxide. Clinical chemistry 28, 2077-2080. https://doi.org/10.1093/clinchem/28.10.2077.

      [16] Friedewald WT, Levy RI, Fredrickson DS (1972). Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clinical chemistry 18, 499-502. https://doi.org/10.1093/clinchem/18.6.499.

      [17] Gaikwad R, Thorat S, Dhemre J (2018). Standardization of Technology for Preparing of Ready to Serve Beverage from Pomegranate fruit. Journal of Krishi Vigyan 6, 218-225. https://doi.org/10.5958/2349-4433.2018.00060.0.

      [18] Gao J, Guo YH, Wang YP, Wang XJ, Xiang WS (2011). A novel and efficient route for the preparation of atorvastatin. Chinese Chemical Letters 22, 1159-1162. https://doi.org/10.1016/j.cclet.2011.04.016.

      [19] Guerrero-Solano JA, Jaramillo-Morales OA, Velázquez-González C, la O-Arciniega D, Castañeda-Ovando A, Betanzos-Cabrera G, Bautista M (2020). Pomegranate as a potential alternative of pain management: a review. Plants 9, 419. https://doi.org/10.3390/plants9040419.

      [20] Guyton JR (2004). Extended-release niacin for modifying the lipoprotein profile. Expert opinion on pharmacotherapy 5, 1385-1398. https://doi.org/10.1517/14656566.5.6.1385.

      [21] Harborne A (1998). Phytochemical methods a guide to modern techniques of plant analysis: springer science & business media.

      [22] Horder M, Elser R, Gerhardt W, Mathieu M, Sampson E (1990). IFCC methods for the measurements of catalytic concentration of enzymes. Journal of the International Federation of Clinical Chemistry 2, 80-83.

      [23] Hossain M, Ahmed M, Islam A (2010). Hypolipidemic and hepatoprotective effects of different fractions of ethanolic extract of immature leaves of Mangifera indica (Linn.) in alloxan induced diabetic rats. International Journal of Pharmaceutical Sciences and Research 1, 132. https://doi.org/10.3923/jms.2010.80.86.

      [24] Hrubec TC, Cardinale JL, Smith SA (2000). Hematology and plasma chemistry reference intervals for cultured tilapia (Oreochromis hybrid). Veterinary clinical pathology 29, 7-12. https://doi.org/10.1111/j.1939-165X.2000.tb00389.x.

      [25] Hua Q, Han Y, Zhao H, Zhang H, Yan B, Pei S, He X, Li Y, Meng X, Chen L (2022). Punicalagin alleviates renal injury via the gut-kidney axis in high-fat diet-induced diabetic mice. Food & function 13, 867-879. https://doi.org/10.1039/D1FO03343C.

      [26] Huang TH, Yang Q, Harada M, Li GQ, Yamahara J, Roufogalis BD, Li Y (2005). Pomegranate flower extract diminishes cardiac fibrosis in Zucker diabetic fatty rats: modulation of cardiac endothelin-1 and nuclear factor-kappaB pathways. Journal of cardiovascular pharmacology 46, 856-862. https://doi.org/10.1097/01.fjc.0000190489.85058.7e.

      [27] Jamdade C, Bodare R, Sadawarti P, Gangavane T (2020). Evaluation of phytochemical and invitro antioxidant study on pomegranate peel. UGC care Journal 68, 48-58.

      [28] Jandal MM, Naji EZ (2021). 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 21, 138-151.

      [29] Kaplan A (1984). Urea. Kaplan A et al. Clin Chem The CV Mosby Co. St Louis. Toronto. Princeton 1984; 1257–1260 and 437 and. 418.

      [30] Kirtipal N, Kumar S, Dubey SK, Dwivedi VD, Babu KG, Malý P, Bharadwaj S (2022). Understanding on the possible routes for SARS CoV-2 invasion via ACE2 in the host linked with multiple organs damage. Infection, Genetics and Evolution, 105254. https://doi.org/10.1016/j.meegid.2022.105254.

      [31] Kushwaha SC, Bera M, Kumar P (2020). Pomegranate. In: Antioxidants in Fruits: Properties and Health Benefits: Springer. p 295-316. https://doi.org/10.1007/978-981-15-7285-2_15.

      [32] Lallianrawna S, Muthukumaran R, Ralte V, Gurusubramanian G, Kumar NS (2013). Determination of total phenolic content, total flavonoid content and total antioxidant capacity of Ageratina adenophora (Spreng.) King & H. Rob. Science vision 13, 149-156.

      [33] Lam CK, Zhang Z, Yu H, Tsang SY, Huang Y, Chen ZY (2008). Apple polyphenols inhibit plasma CETP activity and reduce the ratio of nonâ€HDL to HDL cholesterol. Molecular nutrition & food research 52, 950-958. https://doi.org/10.1002/mnfr.200700319.

      [34] Lei F, Zhang X, Wang W, Xing D, Xie W, Su H, Du L (2007). Evidence of anti-obesity effects of the pomegranate leaf extract in high-fat diet induced obese mice. International journal of obesity 31, 1023-1029. https://doi.org/10.1038/sj.ijo.0803502.

      [35] Li J, Li G, Zhao Y, Yu C (2009). Composition of pomegranate peel polyphenols and its antioxidant activities. Scientia Agricultura Sinica 42, 4035-4041.

      [36] Liman ML, Atawodi SE (2015). Hepatoprotective and nephroprotective effects of methanolic extract of different parts of Tamarindus indica Linn in rats following acute and chronic carbon tetrachloride intoxication. Annual Research & Review in Biology, 109-123. https://doi.org/10.9734/ARRB/2015/8838.

      [37] Lopes-Virella MF, Stone P, Ellis S, Colwell JA (1977). Cholesterol determination in high-density lipoproteins separated by three different methods. Clinical chemistry 23, 882-884. https://doi.org/10.1093/clinchem/23.5.882.

      [38] Lu LS, Wu CC, Hung LM, Chiang MT, Lin CT, Lin CW, Su MJ (2007). Apocynin alleviated hepatic oxidative burden and reduced liver injury in hypercholesterolaemia. Liver International 27, 529-537. https://doi.org/10.1111/j.1478-3231.2007.01451.x.

      [39] Mair J, Wagner I, Jakob G, Lechleitner P, Dienstl F, Puschendorf B, Michel G (1994). Different time courses of cardiac contractile proteins after acute myocardial infarction. Clinica chimica acta 231, 47-60. https://doi.org/10.1016/0009-8981(94)90253-4.

      [40] Mölgaard J, Von Schenck H, Olsson A (1989). Comparative effects of simvastatin and cholestyramine in treatment of patients with hypercholesterolaemia. European journal of clinical pharmacology 36, 455-460. https://doi.org/10.1007/BF00558069.

      [41] Moss D, Henderson A, Kachmar J (1987). Fundamentals of clinical chemistry. Philadelphia 3, 346-421.

      [42] Mushtaq M, Sadique U, Chand N, Ahmed I, Shah S, Ahmad I (2016). Evaluation of Hypolipidemic Activity of Allium schoenoprasum in Albino Rats. British Journal of Pharmaceutical Research 14, 1-10. https://doi.org/10.9734/BJPR/2016/31804.

      [43] Mustafa R, Hamid AA, Mohamed S, Bakar FA (2010). Total phenolic compounds, flavonoids, and radical scavenging activity of 21 selected tropical plants. Journal of Food Science 75, C28-C35. https://doi.org/10.1111/j.1750-3841.2009.01401.x.

      [44] Paget G, Barnes J (1964). Toxicity tests. Evaluation of drug activities: pharmacometrics 1, 135-165. https://doi.org/10.1016/B978-1-4832-2845-7.50012-8.

      [45] Persijn J, van der Slik á (1976). A new method for the determination of γ-glutamyltransferase in serum. https://doi.org/10.1515/cclm.1976.14.1-12.421.

      [46] Prasad K (2010). Effects of vitamin E on serum enzymes and electrolytes in hypercholesterolemia. Molecular and cellular biochemistry 335, 67-74. https://doi.org/10.1007/s11010-009-0243-x.

      [47] Program NCE (2002). Third report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III): The Program. https://doi.org/10.1001/jama.285.19.2486.

      [48] Ramkumar S, Raghunath A, Raghunath S (2016). Statin therapy: review of safety and potential side effects. Acta Cardiologica Sinica 32, 631.

      [49] Richmond W (1992). Analytical reviews in clinical biochemistry: the quantitative analysis of cholesterol. Annals of clinical biochemistry 29, 577-597. https://doi.org/10.1177/000456329202900601.

      [50] Ricketts M-L, Ferguson BS (2018). Polyphenols: novel signaling pathways. Current Pharmaceutical Design 24, 158-170. https://doi.org/10.2174/1381612824666171129204054.

      [51] Ross R, Harker L (1976). Hyperlipidemia and atherosclerosis. Science 193, 1094-1100. https://doi.org/10.1126/science.822515.

      [52] Samoo HA, Maheshwari J, Babar AM, Sheikh AH, Khushk I, Bhutto MA, Khokhar JA, Qureshi AS, Shah SA, Khaskheli AH (2018). Evaluation of the effects of plant aqueous extracts as anti-diabetic agents on alloxan induced diabetic male rabbits. African Journal of Biotechnology 17, 1111-1118. https://doi.org/10.5897/AJB2018.16445.

      [53] Santhi K, Sengottuvel R (2016). Qualitative and quantitative phytochemical analysis of Moringa concanensis Nimmo. Int. J. Curr. Microbiol. App. Sci 5, 633-640. https://doi.org/10.20546/ijcmas.2016.501.064.

      [54] Scaldaferri F, Pizzoferrato M, Ponziani FR, Gasbarrini G, Gasbarrini A (2013). Use and indications of cholestyramine and bile acid sequestrants. Internal and emergency medicine 8, 205-210. https://doi.org/10.1007/s11739-011-0653-0.

      [55] Schumann G, Canalias F, Joergensen PJ, Kang D, Lessinger J-M, Klauke R (2010). IFCC reference procedures for measurement of the catalytic concentrations of enzymes: corrigendum, notes and useful advice. Clinical chemistry and laboratory medicine 48, 615-621. https://doi.org/10.1515/CCLM.2010.137.

      [56] Sharifiyan F, Movahedian-Attar A, Nili N, Asgary S (2016). Study of pomegranate (Punica granatum L.) peel extract containing anthocyanins on fatty streak formation in the renal arteries in hypercholesterolemic rabbits. Advanced biomedical research 5.

      [57] Shattat GF (2015). A review article on hyperlipidemia: types, treatments and new drug targets. Biomedical and Pharmacology Journal 7, 399-409. https://doi.org/10.13005/bpj/504.

      [58] Sun Y, Ge X, Li X, He J, Wei X, Du J, Sun J, Li X, Xun Z, Liu W (2020). High-fat diet promotes renal injury by inducing oxidative stress and mitochondrial dysfunction. Cell Death & Disease 11, 1-14. https://doi.org/10.1038/s41419-020-03122-4.

      [59] Suri A, Singh N, Bansal SK (2021). A Study on the Serum γ-Glutamyltranspeptidase and Plasma Osteopontin in Alcoholic Liver Disease. Journal of Laboratory Physicians. https://doi.org/10.1055/s-0041-1729479.

      [60] Szasz G (1974). New substrates for measuring gamma-glutamyl transpeptidase activity. Zeitschrift fur klinische Chemie und klinische Biochemie 12, 228-228.

      [61] Tamilselvi N, Krishnamoorthy P, Dhamotharan R, Arumugam P, Sagadevan E (2012). Analysis of total phenols, total tannins and screening of phytocomponents in Indigofera aspalathoides (Shivanar Vembu) Vahl EX DC. Journal of Chemical and Pharmaceutical Research 4, 3259-3262.

      [62] Tietz N (1990). Clinical Guide to Laboratory Tests 2nd Ed. Philadelphia. Tovar D, Zambonino-Infante JL, Cahu C, Gatesoupe FJ, Vلzquez-Juلrez R, Lésel R (2002). Effect of live yeast incorporation in compound diet on digestive enzyme activity in sea bass larvae. Aquaculture 204, 113-123. https://doi.org/10.1016/S0044-8486(01)00650-0.

      [63] Tietz NW, Finley PR, Pruden E (1995). Clinical guide to laboratory tests: WB Saunders company Philadelphia.

      [64] Ulla A, Alam MA, Sikder B, Sumi FA, Rahman MM, Habib ZF, Mohammed MK, Subhan N, Hossain H, Reza HM (2017). Supplementation of Syzygium cumini seed powder prevented obesity, glucose intolerance, hyperlipidemia and oxidative stress in high carbohydrate high fat diet induced obese rats. BMC complementary and alternative medicine 17, 1-13. https://doi.org/10.1186/s12906-017-1799-8.

      [65] Vargas R, Vásquez IC (2017). Effects of overfeeding and high-fat diet on cardiosomatic parameters and cardiac structures in young and adult zebrafish. Fish physiology and biochemistry 43, 1761-1773. https://doi.org/10.1007/s10695-017-0407-7.

      [66] Vega GL, Grundy SM (1994). Lipoprotein responses to treatment with lovastatin, gemfibrozil, and nicotinic acid in normolipidemic patients with hypoalphalipoproteinemia. Archives of internal medicine 154, 73-82. https://doi.org/10.1001/archinte.154.1.73.

      [67] Warnick GR, Wood PD (1995). National cholesterol education program recommendations for measurement of high-density lipoprotein cholesterol: Executive summary. The national cholesterol education program working group on lipoprotein measurement. Clinical chemistry 41, 1427-1433. https://doi.org/10.1093/clinchem/41.10.1427.

      [68] Young D (1995). Effects of drugs on Clinical Lab. In: Tests, 4th ed AACC Press.

      [69] Young DS, Friedman RB (2001). Effects of disease on clinical laboratory tests: Amer Assn for Clinical Chemistry.

      [70] Zeng Y-Y, Zhang W-B, Cheng L, Wang L, Geng D-D, Tang W-J, He J-C, Deng B-B (2021). Cardiac parameters affect prognosis in patients with non-large atherosclerotic infarction. Molecular Medicine 27, 1-10. https://doi.org/10.1186/s10020-020-00260-5.

      [71] Zhou T, He X, Fang W, Zhan J, Hong S, Qin T, Ma Y, Sheng J, Zhou N, Zhao Y (2016). Pretreatment albumin/globulin ratio predicts the prognosis for small-cell lung cancer. Medicine 95, e3097. https://doi.org/10.1097/MD.0000000000003097.

    2. lang=EN-US style='font-size:9.0pt;color:red'>
  • Downloads

  • How to Cite

    Afify, A., Hassan, Z., Abd El-Mageed, N., & El-Mahmoudy, A. (2022). Antihyperlipidemic effect of Punica granatum mesocarp extract (PGME) in rats. International Journal of Pharmacology and Toxicology, 10(1), 10-17. https://doi.org/10.14419/ijpt.v10i1.32086

    Received date: 2022-06-01

    Accepted date: 2022-06-29

    Published date: 2022-07-17