Browse > Article

Pomegranate (Punica granatum) as Resources of Phytoestrogen and Anticancer Substances.  

Song, Bang-Ho (Department of Biology Education, Kyungpook National University)
Tran, Hoang Ngoc Ai (Department of Biology Education, Kyungpook National University)
Bae, Soo-Young (Department of Biology Education, Kyungpook National University)
Publication Information
Microbiology and Biotechnology Letters / v.35, no.2, 2007 , pp. 81-97 More about this Journal
Abstract
Punica granatum, L. (Pomegranate) has 613 seeds which accidentally corresponds to the 613 commandments in the Bible. Accordingly, the fruit has been worshipped by the Jewish and other religious people from the ancient. Pomegranate's seed, peel and juice contain a variety of ethnomedical components so much as the sum of three kinds of other common fruits. The number of published papers related to the pomegranate in recent 7 years flourished 7 times more than before at the bases of Medline record. Since the containments of estrogen, as $17{\alpha}-estradiol,\;17{\beta}-estradiol$, estrone, and estradiol, etc., in pomegranate have been reported, public interests and commercial values of pomegranate arose considerably. The report was disproved later, however, merits of this fruit remained yet; clinical efficacy for preventing and remediating cancers including breast and prostate cancers by oral administration of the juice, seed oil, and peel extract is still believed to be true. In this review, target components of pomegranate such as antioxidants, anticancers, antiestrogens and ethnomedical components were analyzed and discussed along with examining its pharmaceutical efficacy and prescription to postmenopausal lesion, cardiosclerosis, cosmetic beautification, viral and allergic symptoms, and diabetes mellitus, etc.
Keywords
Punica granatum L.; pomegranate; anticancer; antiestrogen; antioxidant; ethnomedicine; phytoestrogen;
Citations & Related Records
Times Cited By KSCI : 6  (Citation Analysis)
Times Cited By SCOPUS : 2
연도 인용수 순위
1 강춘기. 1990. 우리나라 과실류의 역사적 고찰, Korean. J. Dietary Culture, 5:301-312
2 김학규, 노치웅, 정병만, 하용근, 신원교. 1994. 석류재배실태조사 및 우량품종 수집(과수재배 및 품질향상 연구), 농진청 보고서. pp. 448-450
3 Ajaikumar, K. B., M. Asheef, B. H. Babu, and J. Padikkala. 2005. The inhibition of gastric mucosal injury by Punica granatum L. (pomegranate) methanolic extract. J. Ethno-Pharmacol. 96: 171-176   DOI   PUBMED   ScienceOn
4 Albertazzi, P. and D. W. Purdie. 2001. The life and times of the estrogen receptors: an interim report. Climacteric 4: 194-202   DOI
5 Albrecht, M., W. Jiang, J. Kumi-Diaka, E. P. Lansky, L. M. Gommersall, A. Patel, R. E. Mansel, I. Neeman, A. A. Geldof, and M. J. Campbell. 2004. Pomegranate extracts potently suppress proliferation, xenograft growth, and invasion of human prostate cancer cells. J. Med. Food 7: 274-283   DOI
6 Cerda, B., C. Soto, M. D. Albaladejo, P. Martinez, F. Sanchez-Gascon, F. Tomas-Barberan, and J. C. Espin. 2006. Pomegranate juice supplementation in chronic obstructive pulmonary disease: a 5-week randomized, double-blind, placebo-controlled trial. Eur. J. Clin. Nutr. 60: 245-253   DOI   ScienceOn
7 Deitch, H. R., J. L. Mershon, and K. E. Clark. 2001. Estrogen receptor ${\beta}$ is the predominant isoform expressed in the brain of adult and fetal sheep. Am. J. Obstet. Gynecol. 184: 1077-1079   DOI   ScienceOn
8 Folkman, J. 1972. Anti-angiogenesis: new concept for therapy of solid tumors. Annals Surgery 175: 409-416   DOI   ScienceOn
9 Hwang, H. J., H. J. Park, H. J. Chung, H. Y. Min, E. J. Park, J. Y. Hong, and S. K. Lee. 2006. Inhibitory effects of caffeic acid phenethyl ester on cancer cell metastasis mediated by the down-regulation of matrix metalloproteinase expression in human HT1080 fibrosarcoma cells. J. Nutr. Biochem. 17: 352-362
10 Lansky, E. P., G. Harrison, P. Froom, and W. G. Jiang. 2005. Pomegranate (Punica granatum) pure chemicals show possible synergistic inhibition of human PC-3 prostate cancer cell invasion across Matrigel. Inves New Drugs 23: 121-122   DOI
11 Lloyd, J. U. 1897. Punica granatum. The Western Druggist, Chicago, May, 8 pp1-9. Reprinted at http://www.swsbm.com/ManualsOther/Punica granatum-Lloyd. PDF
12 Ricci, D., L. Giamperi, A. Bucchini, and D. Fraternale. 2006. Antioxidant activity of Punica granatum fruits. Fitoterapia 77: 310-312   DOI   ScienceOn
13 Satomi, H., K. Umemura, A. Ueno, T. Hatano, T. Okuda, and T. Nora. 1993. Carbonic anhydrase inhibitors from the pericarps of Punica granatum L. Biol. Pharm. Bull. 16: 787-790   DOI   PUBMED   ScienceOn
14 Schubert, S. Y., E. P. Lansky, and I. Neeman. 1999. Antioxidant and eicosanoid enzyme inhibition properties of pomegranate seed oil and fermented juice flavonoids. J. Ethnopharmacol. 66: 11-17   DOI   ScienceOn
15 Seeram, N. P., L. S. Adams, S. M. Henning, Y. Niu, Y. Zhang, M. Ci Nair, and D. Heber. 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   DOI   ScienceOn
16 Yasui, Y., M. Hosokawa, H. Kohno, T. Tanaka, and K. Miyashita. 2006. Growth inhibition and apoptosis induction by all-trans-conjugated linolenic acids on human colon cancer cells. Anticancer Res. 26: 1855-1860   PUBMED
17 Shukla, S. and S. Gupta. 2004. Molecular mechanisms for apigenin-induced cellcycle arrest and apoptosis of hormone refractory human prostate carcinoma DU145 cells. Mol. Carcinog. 39: 114-126   DOI   ScienceOn
18 Smith, R. G. 2000. The aging process: where are the drug opportunities? Curr. Opin. Chem. Biol. 4: 371-376   DOI   ScienceOn
19 Tran H. N. A. and B. H. Song. 2005. Existence of ${\alpha}$-eleostearic acid in pomegranate seed oil and its binding activity against $ER{\alpha}\;&\;ER{\beta}$. Proc. KSMCS Int. Symposium. 13: 205-206
20 Zand, R. S., D. J. Jenkins, and E. P. Diamandis. 2000. Steroid hormone activity of flavonoids and related compounds. Breast Cancer Res. and Treat. 62: 35-49   DOI   ScienceOn
21 Miguel, G., C. Fontes, D. Antunes, A. Neves, and D. Martins. 2004. Anthocyanin concentration of 'Assaria' pomegranate fruits during different cold storage conditions. J. Biomed Biotechnol. 2004: 338-342   DOI   ScienceOn
22 Jahfar, M., K. K. Vijayan, and P. Azadi. 2003. Studies on a polysaccharide from the fruit rind of Punica granatum. Res. J. Chem. Environ. 7: 43-50
23 Langley, P. 2000. Why a pomegranate? B. M. J. 321: 1153-1154   DOI
24 Liu, J., B. Chen, Y. Yang, and X. Wang. 2004. Effect of apoptosis in human mammary cancer (MCF-7) cells induced by cis9, tll-conjugated linoleic acid. Wei Sheng Yan Jiu. 33: 58-62
25 Malik, A., F. Afaq, S. Sarfaraz, V. M. Adhami, D. N. Syed, and H. Mukhtar. 2005. Pomegranate fruit juice for chemoprevention and chemotherapy of prostate cancer. Proc. Natl. Acad Sci. USA 102: 14813-14818
26 Aviram, M., M. Rosenblat, D. Gaitini, S. Nitecki, A. Hoffman, L. Dornfeld, N. Volkova, D. Presser, J. Attias, H. Liker, and T. Hayek. 2004. Pomegranate juice consumption for 3 years by patients with carotid artery stenosis reduces common carotid intima-media thickness, blood pressure and LDL oxidation. Clin. Nutr. 23: 423-433   DOI   ScienceOn
27 Cunningham, D. C., L. Y. Harrison, and T. D. Shultz. 1997. Proliferative responses of normal human mammary and MCF-7 breast cancer cells to linoleic acid, conjugated linoleic acid and eicosanoid synthesis inhibitors in culture. Anticancer Res. 17: 197-203   PUBMED
28 Munde, S. S., V. K. Patil, and S. D. Chavan. 1981. Chemical composition of pomegranate (Punica granatum L.) leaves sampled during different stages of crop. Food Farm. Agr. 13: 177-181
29 Toi, M., H. Bando, C. Ramachandran, S. J. Melnick, A. Imai, R. S. File, R. E. Carr, T. Oikawa, and E. P. Lansky. 2003. Preliminary studies on the anti-angiogenic potential of pomegranate fractions in vitro and in vivo. Angiogenesis 6: 121-128   DOI
30 Aslam, M. N., H. Fligiel, H. Lateef, G. J. Fisher, I. Ginsburg, and J. Varani. 2005. PADMA28: a multi-component herbal preparation with retinoid-like dermal activity but without epidermal effects. J. Invest. Dermatol. 124: 524-529   DOI   ScienceOn
31 Sastravaha, G., G. Gassmann, P. Sangtherapitikul, and W. D. Grimm. 2005. Adjunctive periodontal treatment with Centella asiatica and Punica granatum extracts in supportive periodontal therapy. J. Int. Acad. Periodontol. 7: 70-79   PUBMED
32 Schubert, S. Y., I. Neeman, and N. Resnick. 2002. A novel mechanism for the inhibition of NF-kappaB activation in vascular endothelial cells by natural antioxidants. FASEB (Fed. Amer. Soc. Exp. Biol.) J. 16: 1931-1933
33 Zhu, B. T., G. Z. Han, J. Y. Shim, Y. Wen, and X. R. Jiang. 2006. Quentitative structure-activity relationship of various endogeneous estrogen metabolites for human $ER{\alpha}\;&\;{\beta}$ subtypes: Insights into the structural determinants favoring a differential subtype binding. Endocrinol. 147: 4132-4150   DOI   ScienceOn
34 Kohno, H., R. Suzuki, Y. Yasui, M. Hosokawa, K. Miyashita, and T. Tanaka. 2004. Pomegranate seed oil rich in conjugated linolenic acid suppresses chemically induced colon carcinogenesis in rats. Cancer Science 95: 481-486   DOI   ScienceOn
35 Grosser, T., S. Fries, and G. A. FitzGerald. 2006. Biological basis for the cardiovascular consequences of COX-2 inhibition: therapeutic challenges and opportunities. J. Clin. Invest. 116: 4-15   DOI   ScienceOn
36 Jensen, E. V., G. Cheng, C, Palmieri, S, Saji, S. Makela, S. Van Noorden, T. Wahlstrom, M. Warner, R. C. Coombes, and J. A. Gustafsson. 2001. Estrogen receptors and proliferation markers in primary and recurrent breast cancer. Proc. Natl. Acad. Sci. USA 98: 15197-15202
37 Mori-Okamoto, J., Y. Otawara-Hamamoto, H. Yamato, and H. Yoshimura. 2004. Pomegranate extract improves a depressive state and bone properties in menopausal syndrome model ovariectomized mice. J. Ethnopharmacol. 92: 93-101   DOI   ScienceOn
38 Palmieri, C., G J. Cheng, S. Saji, M. Zelada-Hedman, A. Warri, Z. Weihua, S. Van Noorden, T. Wahlstrom, R. C. Coombes, M. Warner, and J. A. Gustafsson. 2002. Estrogen receptor ${\beta}$ in breast cancer. Endocr. Relat. Cancer. 9: 1-13   DOI   ScienceOn
39 Suzuki, R., R. Noguchi, T. Ota, M. Abe, K. Miyashita, and T. Kawada. 2001. Cytotoxic effect of conjugated trienoic fatty acids on mouse tumor and human monocytic leukemia cells. Lipids 36: 477-482   DOI   ScienceOn
40 Harris, H. A. 2007. Estrogen receptor: Recent lessons from in vivo studies. Mol. Endocrinol. 21: 1-13   DOI
41 Pastorekova, S., S. Parkkila, J. Pastorek, and C. T. Supuran. 2004. Carbonic anhydrases: current state of the art, therapeutic applications and future prospects. J. Enzyme Inhib. Med Chem. 19: 199-229   DOI   ScienceOn
42 Salvi, G. E. and N. P. Lang. 2005. Host response modulation in the management of periodontal diseases. J. Clin. Periodontol. 32: 108-129. Comment: J. Clin. Periodontol. 32: Suppl 6: 130-131   DOI   ScienceOn
43 Seeram, N. P., L. S. Adams, Y. Zhang, R. Lee, D. Sand, H. S. Scheuller, and D. Heber. 2006. Blackberry, black raspberry, blueberry, cranberry, red raspberry, and strawberry extracts inhibit growth and stimulate apoptosis of human cancer cells in vitro. J. Agric. Food. Chem. 54: 9329-9339   DOI   ScienceOn
44 Mehta, R. and E. P. Lansky. 2004. Breast cancer chemopreventive properties of pomegranate (Punica granatum) fruit extracts in a mouse mammary organ culture. Eur. J. Cancer Prev. 13: 345-348   DOI   ScienceOn
45 이성우, 김광수, 김순동. 1974. 석류과실의 성숙에 따른 성분변화에 관한 연구 I, II, J. Kor. Soc. Hort. Sci., 15: 57-71
46 Halvorsen, B. L., K. Holte, M. C. W. Myhrstad, J. Barikmo, E. Hvattum, S. F. Remberg, A-B. Wold, K. Haffner, H. Baugerod, L. F. Andersen, J. O. Moskaug, D. R. Jr. Jacobs, and R. Blorr hoff. 2002. A systematic screening of total antioxidants in dietary plants. J. Nutr. 132: 461-471
47 Wang, R., W. Wang, L. Wang, R. Liu, D. Y Li, and L. Du. 2006. Constituents of the flowers of Punica granatum. Fitoterapia 77: 534-537   DOI   ScienceOn
48 Esmaillzadeh, A., F. Tahbaz, I. Gaieni, H. Alavi-Majd, and L. Azadbakht. 2004. Concentrated pomegranate juice improves lipid profiles in diabetic patients with hyperlipidemia. J. Med. Food 7: 305-308   DOI
49 Larrosa, M., F. A. Tomas-Barberan, and J. C. Espin. 2006. The dietary hydrolysable tannin punicalagin releases ellagic acid that induces apoptosis in human colon adenocarcinoma Caco-2 cells by using the mitochondrial pathway. J. Nutr. Biochem. 17: 611-725   DOI   ScienceOn
50 Cowley, S. M., S. Hoare, S. Mosselman, and M. G. Parker. 1997. Estrogen receptors ${\alpha}\;&{\beta}$ form heterodimers on DNA. J. Biol. Chem. 272: 19858-19862   DOI   ScienceOn
51 Longtin, R. 2003. The pomegranate: nature's power fruit? J. Natl. Cancer Inst. 95: 346-348   DOI   PUBMED   ScienceOn
52 Lansky, E. P., W. Jiang, H. Mo, L. Bravo, P. Froom, W. Yu, N. M. Harris, I. Neeman, and M. J. Campbell. 2005. Possible synergistic prostate cancer suppression by anatomically discrete pomegranate fractions. Invest. New Drugs 23: 11-20   DOI   ScienceOn
53 Tsuzuki, T., Y. Tokuyama, M. Igarashi, and T. Miyazawa. 2004. Tumor growth suppression by ${\alpha}$-eleostearic acid, a linolenic acid isomer with a conjugated triene system, via lipid peroxidation. Carcinogenesis. 25: 1417-1425   DOI   ScienceOn
54 Vidal, A., A. Fallarero, B. R. Pena, M. E. Medina, B. Gra, F. Rivera, Y. Gutierrez, and P. M. Vuorela. 2003. Studies on the toxicity of Punica granatum L. (punicaceae) whole fruit extracts. J. Ethnopharmacol. 89: 295-300   DOI   ScienceOn
55 Ghadirian, P., J. M. Ekoe, and J. P. Thouez. 1992. Food habits and esophageal cancer: an overview. Cancer Detect. Prev. 16: 163-168   PUBMED
56 Jeune, M.A., J. Kumi-Diaka, and J. Brown. 2005. Anticancer activities of pomegranate extracts and genistein in human breast cancer cells. J. Med. Food 8: 469-475   DOI   ScienceOn
57 Kaur, G., Z. Jabbar, M. Athar, and S. Alam. 2006. Punica granatum flower extract possesses potent antioxidant activity and abrogates Fe-NTA induced hepatotoxicity in mice. Food Chem. Toxicol. 44: 984-93   DOI   ScienceOn
58 Tsutsui, T. and I. C. Barrett. 1997. Neoplastic transformation of cultured mammalian cells by estrogens and estrogen like chemicals. Environ. Health. Perspect. 3: 619-624
59 Balkwill, F., K. A. Charles, and A. Mantovani. 2005. Smoldering inflammation in the initiation and promotion of malignant disease. Cancer Cell 7: 211-217   DOI   ScienceOn
60 Khalifah, R. G. 2003. Reflections on Edsall' s carbonic anhydrase: paradoxes of an ultra fast enzyme. Biophy. Chem. 100: 159-170   DOI   ScienceOn
61 Zhu, Y. S., L. Q. Cai, Y. Huang, J. Fish, L. Wang, Z. K. Zhang, and J. L. Imperato-McGinley. 2005. Receptor isoform and ligand-specific modulation of dihydrotestosterone-induced prostate specific antigen gene expression and prostate tumor cell growth by estrogens. J. Androl. 26: 500-510   DOI   ScienceOn
62 Tran H. N. A., S. H. Yoon, Y. S. Bae, and B. H. Song. 2005. Effect of punicic acid in pomegranate seed oil to the human breast cancer cell proliferation. Proc. KSMCS Int. Symposium. 13: 203-204
63 Halicka, H. D., X. Huang, F. Traganos, M. A. King, W. Dai, and Z. Darzynkiewicz. 2005. Histone H2AX phosphorylation after cell irradiation with UV-B: relationship to cell cycle phase and induction of apoptosis. Cell Cycle 4: 339-345   PUBMED
64 Ishunina, T. A., F. P. Kruijver, R. Balesar, and D. F. Swaab. 2000. Differential expression of estrogen receptor ${\alpha}$ and ${\beta}$ immunoreacivity in the human supraoptic nucleus in relation to sex and aging. J. Clin. Endocrinol. Metab. 85: 3283-3291   DOI
65 Mosselman S., J. Polman, R. Dijkema, ER${\beta}$: identification and characterization of a novel human estrogen receptor, FEBS Lett. 392, 49-53, 1996   DOI   ScienceOn
66 Zhu, Y., Z. Bian, P. Lu, R. H. Karas, L. Bao, D. Cox, J. Hodgin, P. W. Shaul, P. Thoren, O. Smithies, J. A. Gustafsson, and M. E. Mendelsohn. 2002. Abnormal vascular function and hypertension in mice deficient in estrogen receptor ${\beta}$. Science 295: 505-508   DOI   ScienceOn
67 Aggarwal, B. B. and S. Shishodia. 2006. Molecular targets of dietary agents for prevention and therapy of cancer. Biochem Pharmacol. 71: 1397-1421   DOI   ScienceOn
68 Johar, D., J. C. Roth, G. H. Bay, J. N. Walker, T J. Kroczak, and M. Los. 2004. Inflammatory response, reactive oxygen species, programmed (necrotic-like and apoptotic) cell death and cancer. Rocz. Akad. Med. Bialymst. 49: 31-39
69 Ozcal, N. and S. Dine, 1993. Evaluation of the pomegranate (Punica granatum L.) peels from the standpoint of pharmacy. Eczacilik Fakultesi Dergisi 22: 21-29
70 Song, R. X. and R. J. Santen. 2003. Apoptotic action of estrogen. Apoptosis 8: 55-60   DOI   ScienceOn
71 Polagruto, J. A., D. D. Schramm, J. F. Wang-Polagruto, L. Lee, and C. L. Keen. 2003. Effects of flavonoid-rich beverages on prostacyclin synthesis in humans and human aortic endothelial cells: association with ex vivo platelet function. J. Med Food 6: 301-308   DOI   ScienceOn
72 Bouker, K. B. and L. Hilakivi-Clarke. 2000. Genistein: does it prevent or promote breast cancer? Environ. Health Perspect. 108: 701-708   DOI
73 Sushanta, K., A. Banerjee, A. Islam, and S. Banerjee, 2005. The regulatory role of estrogen in carcinogenesis: an overview. Phytopharmaceuticals in Cancer Chemoprevention. pp105-121. CRC Press. U.S.A
74 Xu, J., C. J. Guo, J. J. Yang, J. Y. Wei, Y. F. Li, W. Pang, Y. G. Jiang, and S. Cheng. 2005. Intervention of antioxidant system function of aged rats by giving fruit juices with different antioxidant capacities. Zhonghua Yu Fang Yi Xue Za Zhi 39: 80-83   PUBMED
75 Huang, T H. W., G. Peng, B. P. Kota, G. Q. Li, J. Yamahara, B. D. Rouforalis, and Y. Li. 2005. Anti-diabetic action of Punica granatum flower extract: Activiation of PPAR-r and identification of an active component. Toxicol. Appl. Pharmacol. 207: 160-169   DOI   ScienceOn
76 Choi, D. W., J. Y. Kim, S. H. Choi, H. S. Jung, H. J. Kim, S. Y. Cho, C. S. Kang, and S. Y. Chang. 2006. Identification of steroid hormones in pomegranate using HPLC and GC-mass spectrometry. Food Chem. 96: 562-571   DOI   ScienceOn
77 Kawaii, S. and E. P. Lansky. 2004. Differentiation-promoting activity of pomegranate (Punica granatum) fruit extracts in HL-60 human promyelocytic leukemia cells. J. Med. Food 7: 13-18   DOI   ScienceOn
78 Tsuzuki, T., M. Igarashi, and T. Miyazawa. 2004. Conjugated eicosapentaenoic acid (EPA) inhibits transplanted tumor growth via membrane lipid peroxidation in nude mice. J. Nutr. 134: 1162-1166
79 Loren, D. J., N. P. Seeram, R. N. Schulman, and D. M. Holtzman. 2005. Maternal dietary supplementation with pomegranate juice is neuroprotective in an animal model of neonatal hypoxic-ischemic brain injury. Pediatr Res. 57: 858-864   DOI   ScienceOn
80 Newton, K. M., S. D. Reed, L. Grothaus, K. Ehrlich, J. Guiltinan, E. Ludman, and A. Z. Larcroix. 2005, The Herbal Alternatives for Menopause (HALT) Study: background and study design, Endocrinol. 52: 134-46
81 Song, B. H., K. S. Song, J. G. Kim, Y. H. Kim, Y. B. Seu, S. Y. Ghim, J. M. Lee, and S. H. Kim. 2005. Development of functional food using Reinforced antioxidants and phytoestrogens from Punica granatum. Final Report for ARPC Project. pp19-100, Ministry of Agriculture, Seoul, Korea
82 Manas, E. S., R. J. Unwalla, Z. B. Xu, M. S. Malamas, C. P. Miller, H. A. Harris, C. Hsiao, T. Akopian, W. T. Hum, K. Malakian, S. Wolfrom, A. Bapat, R. A. Bhat, M. L. Stahl, W. S. Somers, and J. C. Alvarez. 2004. Structure-based design of estrogen receptor-${\beta}$ selective ligands. J. Am. Chem. Soc. 126: 15106-15119   DOI   ScienceOn
83 Afaq, F., M. Saleem, C. G Krueger, J. D. Reed, and H. Mukhtar. 2005. Anthocyanin-and hydrolyzable tannin-rich pomegranate fruit extract modulates MAPK and NF-kB pathways and inhibits skin tumorigenesis in CD-1 mice. Int. J. Cancer 113: 423-433   DOI   ScienceOn
84 Henry, R. P. and E. R. Swenson. 2000. The distribution and physiological significance of carbonic anhydrase in vertebrate gas exchange organs. Resp. Physiol. 121: 1-12   DOI   ScienceOn
85 Karaer, O., S. Oruc, and F. M. Koyuncu. 2004. Aromatase inhibitors: possible future applications. Acta Obstet. Gynecol. Scand. 83: 699-706   DOI   ScienceOn
86 Azadzoi, K. M., R. N. Schulman, M. Aviram, and M. B. Siroky. 2005. Oxidative stress in arteriogenic erectile dysfunction: prophylactic role of antioxidants. J. Urol. 174: 386-393   DOI   ScienceOn
87 Liu, J., J. E. Burdette, Y. Sun, S. Deng, S. M. Schlecht, W. Zheng, D. Nikolic, G Mahady, R. B. van Breemen, H. H. Fong, J. M. Pezzuto, J. L. Bolton, and N. R. Farnsworth. 2004. Isolation of linoleic acid as an estrogenic compound from the fruits of V. agnus-castus L. Phytomedicine 11: 18-23   DOI   ScienceOn
88 Maru, I., J. Ohnishi, S. Yamaguchi, Y. Oda, K. Kakehi, and Y. Ohta. 2001. An estrogen-like activity in pomegranate juice. Nippon Shokuhin Kagaku Kogaku Kaishi 48: 146-149   DOI
89 Bachrach, U. 2004. Polyamines and cancer: minireview article. Amino Acids 26: 307-309
90 Hora, J. J., E., R. Maydew, E. P. Lansky, and C. Dwivedi. 2003. Chemopreventive effects of pomegranate seed oil on skin tumor development in CD1 mice. J. Med. Food 6: 157-161   DOI   ScienceOn
91 Afaq, F., A. Malik, D. Syed, D. Maes, M. S. Matsui, and H. Mukhtar. 2005. Pomegranate fruit extract modulates UV-B-mediated phosphorylation of mitogen-activated protein kinases and activation of NF-${\kappa}$B in normal human epidermal keratinocytes paragraph sign. Photochem. and Photobiol. 81: 38-45   DOI   ScienceOn
92 Sharaf, A. and S. A. R. Nigm. 1964. The estrogenic activity of pomegranate seed oil, J. Endocrinol. 29: 91-92   DOI   ScienceOn
93 Simmons, D. L. and C. D. Buckley. 2005. Some new, and not so new, antiinflammatory targets. Curr. Opinion Pharmacol. 5: 394-397   DOI   ScienceOn
94 Fatope, M. O., S. K. Al Burtomani, and Y. Takeda. 2002. Monoacylglycerol from Punica granatum seed oil. J. Agr. Food Chem. 50: 357-360   DOI   ScienceOn
95 Kim, N.D., R. Mehta, W. Yu, I. Neeman, T Livney, A. Amichay, D. Poirier, P. Nicholls, A. Kirby, W. Jiang, R. Mansel, C. Ramachandran, T. Rabi, B. Kaplan, and E. Lansky. 2002. Chemopreventive and adjuvant therapeutic potential of pomegranate (Punica granatum) for human breast cancer. Breast Cancer Res. Treat. 71: 203-217   DOI   ScienceOn
96 Lansky E. P. and R. A. Newman. 2007. Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer. J. Ethnopharmacol. 109: 177-206   DOI   ScienceOn
97 Liu, J. and N. Sidell. 2005. Anti-estrogenic Effects of Conjugated Linoleic Acid through Modulation of Estrogen Receptor Phosphorylation.. Breast. Cancer. Res. Treat. 2005 94: 161-169   DOI
98 Jung, K.H., M. J. Kim, E. Ha, Y. K. Uhm, H. K. Kim, J. H. Chung, and S. V. Yim. 2006. Suppressive effect of Punica granatum on the production of tumor necrosis factor (Tnf) in BV2 microglial cells. Biol. Pharm. Bull. 29: 1258-1261   DOI   ScienceOn
99 Pantuck, A. J., N. Zomorodian, and A. S. Belldegrun. 2006. Phase-II study of pomegranate juice for men with prostate cancer and increasing PSA. Cur. Urol. Rep. 7: 7
100 Hartman, R. E., A. Shah, A. M. Fagan, K. E. Schwetye, M. Parsadanian, R. N. Schulman, M. B. Firm, and D. M. Holtzman. 2006. Pomegranate juice decreases amyloid load and improves behavior in a mouse model of Alzheimer's disease. Neurobiol Dis. 24: 506-515   DOI   ScienceOn
101 Pantuck, A. J., J. T. Leppert, N. Zomorodian, W. Aronson, J. Hong, R. J. Barndard, M. Seera, H. Liker, H. Wang, R. Elashoff, D. Heber, M. Aviram, L. Ignarro, and A. Belldegrun. 2006. Phase II study of pomegranate juice for men with rising prostate-specific antigen following surgery or radiation for prostate cancer. Clin. Cancer Res. 12: 4018-4026   DOI   ScienceOn
102 Settheetham, W. and T. Ishida, 1995. Study of genotoxic effects of antidiarrheal medicinal herbs on human cells in vitro. The Southeast Asian J. Trop. Med. Public Health 26: 306-310
103 Noguchi, K., K. Iwasaki, H. Endo, H. Kondo, M. Shitashige, and I. Ishikawa. 2000. Prostaglandins E2 and I2 downregulate tumor necrosis factor alphainduced intercellular adhesion molecule-1 expression in human oral gingival epithelial cells. Oral Microbiol. Immunol. 15: 299-304   DOI   ScienceOn
104 Kim, M.M. and S. Kim. 2002. Composition for improving oral hygiene containing Punica granatum L. extract. Korean Patent: KR 2002066042