Aldose reductase inhibitory activity and antioxidant capacity of pomegranate extracts

Karasu, Çimen; Cumaoğlu, Ahmet; Gúrpinar, Ali; Kartal, Murat; Kovacikova, Lucia; Milackova, Ivana; Stefek, Milan

doi:10.2478/v10102-012-0003-8

Abstract

The pomegranate, Punica granatum L., has been the subject of current interest as a medicinal agent with wide-ranging therapeutic indications. In the present study, pomegranate ethanolic seed and hull extracts were tested, in comparison with a commercial sample, for the inhibition of aldose reductase, an enzyme involved in the etiology of diabetic complications. In vitro inhibition of rat lens aldose reductase was determined by a conventional method. Pomegranate ethanolic hull extract and commercial pomegranate hull extract exhibited similar aldose reductase inhibitory activity characterized by IC₅₀ values ranging from 3 to 33.3 μg/ml. They were more effective than pomegranate ethanolic seed extract with IC₅₀ ranging from 33.3 to 333 μg/ml. Antioxidant action of the novel compounds was documented in a DPPH test and in a liposomal membrane model, oxidatively stressed by peroxyl radicals. All the plant extracts showed considerable antioxidant potential in the DPPH assay. Pomegranate ethanolic hull extract and commercial pomegranate hull extract executed similar protective effects on peroxidatively damaged liposomal membranes characterized by 10 < IC₅₀ < 100 μg/ml. Pomegranate ethanolic seed extract showed significantly lower antioxidant activity compared to both hull extracts studied. Pomegranate extracts are thus presented as bifunctional agents combining aldose reductase inhibitory action with antioxidant activity and with potential therapeutic use in prevention of diabetic complications.

References

Alexiou P, Pegklidou K, Chatzopoulou M, Nicolaou I, Demopoulos VJ. (2009). Aldose reductase enzyme and its implication to major health problems of the 21(st) century. Curr Med Chem 16: 734-752.
Search in Google Scholar
Artik N. (1998). Determination of phenolic compounds in pomegranate juice by using HPLC. Fruit Processing 8: 492-499
Search in Google Scholar
Bagri P, Ali M, Aeri V, Bhowmik M, Sultana S. (2009). Antidiabetic effect of Punica granatum flowers: effect on hyperlipidemia, pancreatic cells lipid peroxidation and antioxidant enzymes in experimental diabetes. Food Chem Toxicol 47: 50-54.
Search in Google Scholar
Bell C, Hawthorne S. (2008). Ellagic acid, pomegranate and prostate cancer - a mini review. J Pharm Pharmacol 60: 139-144.
Search in Google Scholar
Blois, M. S. (1958). Antioxidant determinations by the use of a stable free radical. Nature 181: 1199-1200.
Search in Google Scholar
Cerda B, Espin JC, Parra S, Martinez P, Tomas-Barberan FA. (2004). The potent in vitro antioxidant ellagitannins from pomegranate juice are metabolised into bioavailable but poor antioxidant hydroxy-6H-dibenzopyran-6-one derivatives by the colonic microflora of healthy humans. Eur J Nutr 43: 205-220.
Search in Google Scholar
Chidambara Murthy KN, Jayaprakasha GK, Singh RP. (2002). Studies on antioxidant activity of pomegranate (Punica granatum) peel extract using in vivo models. J Agric Food Chem 50: 4791-4795.
Search in Google Scholar
Constantino L, Rastelli G, Gamberini MC et al., (1999). 1-Benzopyran-4-one antioxidants and aldose reductase inhibitors. J Med Chem 42: 1881-1893.
Search in Google Scholar
Coudert P, Albuisson E, Boire JY, Duroux E, Bastide P, Couquelet J. (1994). Synthesis of pyridazine acetic acid derivatives possessing aldose reductase inhibitory activity and antioxidant properties. Eur J Med Chem 29: 471-477.
Search in Google Scholar
Das AK, Mandal SC, Banerjee SK, Sinha S, Saha BP, Pal M. (2001). Studies on the hypoglycaemic activity of Punica granatum seed in streptozotocin induced diabetic rats. Phytother Res 15: 628-629.
Search in Google Scholar
Da Settimo F, Primofiore G, La Motta C, Sartini S, Taliani S, Simorini F, Marini AM, Lavecchia A, Novellino E, Boldrini E. (2005). Naphtho[1,2-d]isothiazole acetic acid derivatives as a novel class of selective aldose reductase inhibitors. J Med Chem 48: 6897-907.
Search in Google Scholar
Del Corso A, Cappiello M, Mura U. (2008). From a dull enzyme to something else: facts and perspectives regarding aldose reductase. Curr Med Chem 15: 1452-1461.
Search in Google Scholar
Dikmen M, Ozturk N, Ozturk Y. (2011). The antioxidant potency of Punica granatum L. Fruit peel reduces cell proliferation and induces apoptosis on breast cancer. J Med Food 14:1638-46.
Search in Google Scholar
El Kar C, Ferchichi A, Attia F, Bouajila J. (2011). Pomegranate (Punica granatum) juices: chemical composition, micronutrient cations, and antioxidant capacity. J Food Sci 76: C795-C800.
Search in Google Scholar
Gil MI, Tomas-Barberan FA, Hess-Pierce B, Holcroft DM, Kader AA. (2000). Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing. J Agric Food Chem 48: 4581-4589.
Search in Google Scholar
Hamada Y, Araki N, Horiuchi S, Hotta N. (1996). Role of polyol pathway in nonenzymatic glycation. Nephrol Dial Transplant 11 (Suppl): 95-98.
Search in Google Scholar
Hayman S, Kinoshita JH. (1965). Isolation and properties of lens aldose reductase. J Biol Chem 240: 877-882.
Search in Google Scholar
Han DH, Lee MJ, Kim JH. (2006). Antioxidant and apoptosis-inducing activities of ellagic acid. Anticancer Research 26: 3601-3606.
Search in Google Scholar
Hontecillas R, O'Shea M, Einerhand A, Diguardo M, Bassaganya-Riera J. (2009). Activation of PPAR gamma and alpha by punicic acid ameliorates glucose tolerance and suppresses obesity-related inflammation. J Am Coll Nutr 28: 184-195.
Search in Google Scholar
Huang TH, Peng G, Kota BP, Li GQ, Yamahara J, Roufogalis BD, Li Y. (2005). Anti-diabetic action of Punica granatum flower extract: activation of PPAR-gamma and identification of an active component. Toxicol Appl Pharmacol 207: 160-169.
Search in Google Scholar
Jafri MA, Aslam M, Javed K, Singh S. (2000). Effect of Punica granatum Linn. (flowers) on blood glucose level in normal and alloxan-induced diabetic rats. Journal of Ethnopharmacology 70: 309-314.
Search in Google Scholar
Joseph MM, Aravind SR, Varghese S, Mini S, Sreelekha TT. (2011). Evaluation of antioxidant, antitumor and immunomodulatory properties of polysaccharide isolated from fruit rind of Punica granatum. Mol Med Report doi: 10.3892/mmr.2011.638. [Epub ahead of print].10.3892/mmr.2011.63822012001
Search in Google Scholar
Juranek I, Horakova L, Rackova L, Stefek M. (2009). Antioxidants in treating pathologies involving oxidative damage: an update on medicinal chemistry and biological activity of stobadine and related pyridoindoles. Curr Med Chem 17: 552-570.
Search in Google Scholar
Jurenka JS. (2008). Therapeutic applications of pomegranate (Punica granatum L.): a review. Altern Med Rev. 13: 128-144.
Search in Google Scholar
Kador PF. (1998). The role of aldose reductase in the development of diabetic complications. Med Res Rev 8: 325-352.
Search in Google Scholar
Kador PF, Lee JW, Fujisawa S, Blessing K, Lou MF. (2000). Relative importance of aldose reductase versus nonenzymatic glycosylation on sugar cataract formation in diabetic rats. J Ocul Pharmacol Ther 16: 149-160.
Search in Google Scholar
Katz SR, Newman RA, Lansky EP. (2007). Punica granatum: heuristic treatment for diabetes mellitus. J Med Food 10: 213-217.
Search in Google Scholar
Kinoshita JH. (1990). A thirty-year journey in the polyol pathway. Exp Eye Res 50: 567-573.
Search in Google Scholar
Kyselova Z, Stefek M, Bauer V. (2004). Pharmacological prevention of diabetic cataract. J Diabetes Complications 18: 129-140.
Search in Google Scholar
Kulkarni AP, Aradhya SM, Divakar S. (2004). Isolation and identification of a radical scavenging antioxidant-punicalagin from pith and carpellary membrane of pomegranate fruit. Food Chem 87: 551-557.
Search in Google Scholar
Lansky EP. (2006). Beware of pomegranates bearing 40% ellagic acid. J Med Food 9: 119-122.
Search in Google Scholar
Lansky EP, Newmana RA. (2007). Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. Journal of Ethnopharmacology 109: 177-206.
Search in Google Scholar
Li Y, Qi Y, Huang TH, Yamahara J, Roufogalis BD. (2008). Pomegranate flower: a unique traditional antidiabetic medicine with dual PPAR-alpha/-gamma activator properties. Diabetes Obes Metab 10: 10-17.
Search in Google Scholar
Li Y, Wen S, Kota BP, Peng G, Li GQ, Yamahara J, Roufogalis BD. (2005). Punica granatum flower extract, a potent alpha-glucosidase inhibitor, improves postprandial hyperglycemia in Zucker diabetic fatty rats. J Ethnopharmacol 99: 239-244.
Search in Google Scholar
Mihaljevic B, Katusin-Razem B, Razem B. (1996). The reevaluation of the ferric thiocyanate assay for lipid hydroperoxides with special considerations of the mechanistic aspects of the response. Free Radic Biol Med 21: 53.
Search in Google Scholar
Naz S, Siddiqi R, Ahmad S, Rasool SA, Sayeed SA. (2007). Antibacterial activity directed isolation of compounds from Punica granatum. J Food Sci 72: M341-M345.
Search in Google Scholar
Negi PS, Jayaprakasha GK, Jena BS. (2003). Antioxidant and antimutagenic activities of pomegranate peel extracts. Food Chemistry 80: 393-397.
Search in Google Scholar
Oates PJ. (2008). Aldose reductase, still a compelling target for diabetic neuropathy. Curr Drug Targets 9: 14-36.
Search in Google Scholar
Obrosova IG. (2005). Increased sorbitol pathway activity generates oxidative stress in tissue sites for diabetic complications. Antioxid Redox Signal 7: 1543-1552.
Search in Google Scholar
Rout S, Banerjee R. (2007). Free radical scavenging, anti-glycation and tyrosinase inhibition properties of a polysaccharide fraction isolated from the rind from Punica granatum. Bioresour Technol 98: 3159-3163.
Search in Google Scholar
Scott JA, King GL. (2004). Oxidative stress and antioxidant treatment in diabetes. Ann N Y Acad Sci 1031: 204-213.
Search in Google Scholar
Seeram NP, Adams LS, Henning SM, Niu Y, Zhang Y, Nair MG, Heber D. (2005). In vitro antiproliferative, apoptotic and antioxidant activities of punicalagin, ellagic acid and a total pomegranate tannin extract are enhanced in combination with other polyphenols as found in pomegranate juice. J Nutr Biochem 16: 360-367.
Search in Google Scholar
Singh RP, Chidambara Murthy KN, Jayaprakasha GK. (2002). Studies on the antioxidant activity of pomegranate (Punica granatum) peel and seed extracts using in vitro models. J Agric Food Chem 50: 81-86.
Search in Google Scholar
Stefek M. (2011). Natural flavonoids as potential multifunctional agents in prevention of diabetic cataract. Interdisc Toxicol 4: 101-109.
Search in Google Scholar
Stefek M, Karasu C. (2011). Eye lens in aging and diabetes. Effect of quercetin. Rejuvenation Research 14: 525-534.
Search in Google Scholar
Stefek M, Snirc V, Djoubissie PO, Majekova M, Demopoulos V, Rackova L, Bezakova Z, Karasu C, Carbone V, El-Kabbani O. (2008). Carboxymethylated pyridoindole antioxidants as aldose reductase inhibitors: Synthesis, activity, partitioning, and molecular modeling. Bioorg Med Chem 16: 4908-4920.
Search in Google Scholar
Sun Hui, Jia Dong-ying, Yao Kai. (2008). inhibitory effect of polyphenol extract from pomegranate peel on aldose reductase activity. Natural Product Research And Development 20 (3): 508-510.
Search in Google Scholar
Ueda H, Kawanishi K, Moriyasu M. (2004). Effects of ellagic acid and 2-(2,3,6-trihydroxy-4-carboxyphenyl)ellagic acid on sorbitol accumulation in vitro and in vivo Biol. Pharm Bull 27: 1584-1587.
Search in Google Scholar
Walid Elfalleh, Nizar Tlili, Nizar Nasri, Yassine Yahia, Hedia Hannachi, Nizar Chaira, Ma Ying, Ali Ferchichi. (2011). Antioxidant capacities of phenolic compounds and tocopherols from tunisian pomegranate (Punica granatum). Fruits Journal of Food Science 76: C707-C713.
Search in Google Scholar
Wang R, Ding Y, Liu R, Xiang L, Du L. (2010). Pomegranate: constituents, bioactivities and pharmacokinetics. fruit, Vegetable and Cereal Science and Biotechnology Special Issue 2: 77-87.
Search in Google Scholar
Yabe-Nishimura C. (1998). Aldose reductase in glucose toxicity: a potential target for the prevention of diabetic complications. Pharmacol Rev 50: 21-33.
Search in Google Scholar
Zahin M, Aqil F, Ahmad I. (2010). Broad spectrum antimutagenic activity of antioxidant active fraction of punica granatum L. peel extracts. Mutat Res 703: 99-107.
Search in Google Scholar

Aldose reductase inhibitory activity and antioxidant capacity of pomegranate extracts

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