Pomegranate (Punica granatum) Peel Extract Efficacy as a Dietary Antioxidant against Azoxymethane-Induced Colon Cancer in Rat

  • Waly, Mostafa I. (Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University) ;
  • Ali, Amanat (Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University) ;
  • Guizani, Nejib (Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University) ;
  • Al-Rawahi, Amani S. (Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University) ;
  • Farooq, Sardar A. (Department of Biology, College of Science, Sultan Qaboos University) ;
  • Rahman, Mohammad S. (Department of Food Science and Nutrition, College of Agricultural and Marine Sciences, Sultan Qaboos University)
  • Published : 2012.08.31


Functional foods include antioxidant nutrients which may protect against many human chronic diseases by combating reactive oxygen species (ROS) generation. The purpose of the present study was to investigate the protective effect of pomegranate peel extract (PPE) on azoxymethane (AOM)-induced colon tumors in rats as an in vivo experimental model. Forty Sprague-Dawley rats (4 weeks old) were randomly divided into 4 groups containing 10 rats per group, and were treated with either AOM, PPE, or PPE plus AOM or injected with 0.9% physiological saline solution as a control. At 8 weeks of age, the rats in the AOM and PPE plus AOM groups were injected with 15 mg AOM/kg body weight, once a week for two weeks. After the last AOM injection, the rats were continuously fed ad-libitum their specific diets for another 6 weeks. At the end of the experiment (i.e. at the age of 4 months), all rats were killed and the colon tissues were examined microscopically for lesions suspected of being preneoplastic lesions or tumors as well as for biochemical measurement of oxidative stress indices. The results revealed a lower incidence of aberrant crypt foci in the PPE plus AOM administered group as compared to the AOM group. In addition, PPE blocked the AOM-induced impairment of biochemical indicators of oxidative stress in the examined colonic tissue homogenates. The results suggest that PPE can partially inhibit the development of colonic premalignant lesions in an AOM-induced colorectal carcinogenesis model, by abrogating oxidative stress and improving the redox status of colonic cells.


  1. Adhami VM, Khan N, Mukhtar H (2009). Cancer chemoprevention by pomegranate: laboratory and clinical evidence. Nutr Cancer, 61, 811-5.
  2. Al-Numair KS, Waly MI, Ali A, et al(2011). Dietary folate protects against azoxymethane-induced aberrant crypt foci development and oxidative stress in rat colon. Exp Biol Med, 236, 1005-1.
  3. Anilakumar KR, Sudarshanakrishna KR, Chandramohan G, et al (2010). Effect of Aloe vera gel extract on antioxidant enzymes and azoxymethane-induced oxidative stress in rats. Indian J Exp Biol,48, 837-42.
  4. Bird RP (1995). Role of aberrant crypt foci in understanding the pathogenesis of colon cancer. Cancer Lett, 93, 55-71.
  5. Bussuan LA, Fagundes DJ, Marks G, et al (2010). The role of Fas ligand protein in the oxidative stress induced by azoxymethane on crypt colon of rats. Acta Cir Bras, 25, 501-6.
  6. Chidambara-Murthy KN, Jayaprakasha GK, Singh RP (2002). Studies on antioxidant activity of pomegranate (Punica Grantum) peel extract using in vivo models. J Agric Food Chem, 50, 4791-5.
  7. Cuccioloni M, Mozzicafreddo M, Sparapani L, et al (2009). Pomegranate fruit components modulate human thrombin. Fitoterapia, 80, 301-5.
  8. Esfahani A, Wong JM, Truan J, et al (2011). Health effects of mixed fruit and vegetable concentrates: a systematic review of the clinical interventions. J Am Coll Nutr, 30, 285-94.
  9. Gulcin I (2012). Antioxidant activity of food constituents: an overview. Arch Toxicol, 86, 345-91.
  10. Hangen L, Bennink MR (2002). Consumption of black beans and navy beans (Phaseolus vulgaris) reduced azoxymethane-induced colon cancer in rats. Nutr Cancer, 44, 60-5.
  11. Hu ML (2011). Dietary polyphenols as antioxidants and anticancer agents: morequestions than answers. Chang Gung Med J, 34, 449-60.
  12. Lansky EP, Newman RA (2007). Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J Ethnopharmacol, 109, 177-206.
  13. Leonardi T, Vanamala J, Taddeo SS, et al (2010). Apigenin and naringenin suppress colon carcinogenesis through the aberrant crypt stage in azoxymethane-treated rats. Exp Biol Med, 235, 710-7.
  14. Lowry OH, Rosebrough NJ, Fait AL, et al (1951). Protein measurement with the Folin phenol reagent. J Biol Chem, 193, 265-75.
  15. Pande G, Akoh CC(2009). Antioxidant capacity and lipid characterization of six Georgia-grown pomegranate cultivars. J Agric Food Chem, 57, 9427-36.
  16. Ramadan A, El-Badrawey S, Abd El-Ghany M, et al(2009). Rind and juice of pomegranate as natural antioxidants in cotton seed oil. The 5th Arab Annual Scientific Conference, Egypt, 8-9 April.
  17. Rodriguez-Ramiro I, Ramos S, Lopez-Oliva E, et al (2011). Cocoa-rich diet prevents azoxymethane-induced colonic preneoplastic lesions in rats by restraining oxidative stress and cell proliferation and inducing apoptosis. Mol Nutr Food Res, 55, 1895-9.
  18. Shiraishi R, Fujise T, Kuroki T, et al (2009). Long-term ingestion of reduced glutathione suppressed an accelerating effect of beef tallow diet on colon carcinogenesis in rats. Gastroenterol, 44, 1026-35.
  19. 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, 81-6.
  20. Singleton L, Rossi A (1965). Colorimetry of total phenolics with phosphomolybdic phosphotungstic acid reagents. Am J Enology Viticulture, 16, 144-58.
  21. Tsunada S, Iwakiri R, Noda T, et al (2003). Chronic exposure to subtoxic levels of peroxidized lipids suppresses mucosal cell turnover in rat small intestine and reversal by glutathione. Dig Dis Sci, 48, 210-22.

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