The Magic of Plants

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exotic-fruitslarge             IMG_1117

Wolfberries       perfect fruits

 

It is no small wonder that nearly seventy percent of all industrialized populations are either overweight or obese and that the accompanying incidence of Type 2 Diabetes is also exploding.

At the root of this phenomenon is the metabolic syndrome, a condition characterized by increased levels of free radicals, also called reactive oxygen species (ROS), and decreased antioxiant capacity of the tissue (the ability of the tissue to neutralize these ROS through antioxidant enzyme systems, compounds, and vitamins).  It is a key promoter of all diseases, is developed through caloric excess (particularly in the form of highly refined carbohydrates and animal fat) and sedentery lifestyle, and its symptoms include obesity, hypertension, insulin resistance, inflammation, abnormal lipid concentrations, and a chronically vasoconstricted, proinflammatory, prothrombotic state, which leads to decreased tissue blood flow.  We can combat this insidious condition and the chronic diseases that follow with frequent exercise and a whole foods, plant based diet.

Fruit Benefit Chart

Multiple epidemiologic studies have shown lower morbidity and mortality in patients who consume a wide variety of fruits and vegetables compared to those who don’t.  A large body of research supports the concept that nutritional magic bullets are found within these natural fruits and vegetables that we have eaten since the beginning of time.

Heartberry

naturally-occurring-phenolic-compounds

They are called plant polyphenols, have multiple hydroxylated benzene rings which serve as a plentiful source of electrons used to quench free radicals (oxidants), and are the most potent natural antioxidants known to man. There are thousands of polyphenols in fruits and vegetables (see tables below).

After learning everything I could about these fascinating compounds, I set out on a mission to create one supplement that could contain the widest variety of these compounds in the fewest number of capsules possible, something that had never been done before. I then chose the most well known and researched polyphenols from each class that showed that the greatest health benefits, were synergistic with each other, and could be put into a vehicle that allowed the best absorption through the gut to achieve the highest possible blood and tissue levels (greatest bioavailability). This would allow me and others to receive tremendous benefits from swallowing just a few capsules each day- a much more realistic and reproducible daily goal than what had been available until now. In fact, to get the same tissue levels of the compounds listed below, one would need to take at least twice as many capsules from different bottles per day, and pay hundreds of dollars more per month. Below are the compounds that I have included.

Flavones

Trans-Resveratrol (Flavonoid)Responsible for the “French Paradox”, the greatly reduced incidence of atherosclerotic vascular disease in the French (who consume greater quantities of red wine), this compound has been shown to slow aging, and promote weight loss, along with anti-inflammatory, antidiabetic, antifungal, antiviral, antibacterial, antiallergic, anticancer, antihypertensive, antidyslipidemic, and cardioprotective properties, to name a few (6-17). One would have to drink more than 250 glasses of red wine per day to get the same amount provided in our daily dose.
Most well known benefits- Promotes Cardiovascular Health

Curcumin (Hydroxycinnamic Acid Derivative):  For centuries, Indians have used this spice also named Curry from the root of the Turmeric plant (also named curry) for its therapeutic properties. They are largely the same as those above (18-24), and one would have to consume roughly 2 lb of yellow mustard or 6 Tablespoons of pure Turmeric each day to get the amount we provide in one daily dose.
Most well known benefits- Antiinflammatory, promotes liver and brain health.

EGCG (Flavonoid):  EGCG is the key active component in Green Tea, which has been consumed for centuries by the Chinese and other cultures for its therapeutic benefits, again similar to those above (25-33). Studies have shown weight loss in subjects receiving daily doses less than this both within and without phytosome vehicles (33, 49).  One would have to consume over 20 cups of green tea per day to receive the daily dose of EGCG we provide.
Most well known benefits- Promotes healthy immune and cardiovascular function, and supports metabolism and weight loss.

Silymarin (Flavolignan):  This is a polyphenolic derived from the milk thistle plant, which has been used since Greco-Roman times for its antioxidant, anti-inflammatory, anticancer, antihypertensive, antidiabetic, neuro, hepato, and renoprotective effects (70-98). One would have to consume several milk thistle plants per day to receive the daily dose of Silymarin we provide.
Most well known benefit- Promotes healthy liver function.

Punicaligans (Phenolic Acid):  The Pomegranate, Punica Granatum, has been grown in the Mediterranean region since the Old Testament, and has been studied for its antioxidant, anticancer, anti-inflammatory, antidiabetic, antiobesity, antialzheimers, antihypertensive, antiatherosclerotic, antidyslipidemic, and cardio and cerebroprotective activities (99-125). Of the multiple Ellagitanins contained within the fruit, Punicalagins appear to be responsible for many of these health benefits (126). One would have to eat over 60 pomegranates to get the same dose we provide.
Most well known benefits- Promotes overall cellular and cardiovascular health. 

Phosphatidylcholine (Phospholipid): Because it is the major component of all cell membranes, it serves as the phytosome (liposome) complex absorption vehicle for the polyphenols. Because it is a fat, it encircles the other compounds and provides them with an outer lipid layer which promotes greater absorption through the lipid membranes of the gut lining cells and into the circulation, thereby increasing blood and tissue levels. Then it allows for easy incorporation into the membranes of all cells. Such phytosomes can increase bioavailability of the above plant polyphenols by up to 6-fold (49, 51), increasing their tissue levels and therapeutic effects (48-58).
Most well known benefits- Cell membrane composition and repair, precursor for Acetylcholine, a critical neurotransmitter, maintains brain and gastrointestinal health, and reduces harmful homocysteine levels. One would have to eat 1/2 cup of raw soybeans to get this much PC.  

PhytoLife Torus

PhytoLife Torus

Through personal experience, medical science, and a desire to provide a reasonable number of pills with the greatest synergy and therapeutic benefit, I have come up with the optimal superantioxidant. Of course, it is not all you need, but along with the proper Mediterranean Diet, functional foods, and plenty of exercise, it is the best and simplest antioxidant supplement I could create.

1.  Potenza, M.V. & Mechanick, J.I. 2009, “The metabolic syndrome: Definition, global impact, and pathophysiology”, Nutrition in Clinical Practice, vol. 24, no. 5,   pp. 560-577.

2. Cohen, R.A. & Tong, X. 2010,”Vascular oxidative stress: The common link in hypertensive and diabetic vascular disease”, Journal of cardiovascular pharmacology, vol. 55, no. 4, pp. 308-316.

3. Lorgeril, M. & Salen, P.2008, “The mediterranean diet: Rationale and evidence for its benefit”, Current atherosclerosis reports, vol. 10, no. 6, pp. 518-522.

4. Sirtori, C.R., Galli, C.,Anderson, J.W., Sirtori, E. & Arnoldi, A. 2009, “Functional foods for dyslipidaemia and cardiovascular risk prevention”, Nutrition Research Reviews, vol. 22,no. 2, pp. 244-261.

5. Najm, W. & Lie, D. 2008,”Dietary Supplements Commonly Used for Prevention”, Primary Care -Clinics in Office Practice, vol. 35, no. 4, pp. 749-767.

Trans-resveratrol

6. Bertelli, A.A.A. & Das, D.K.2009, “Grapes, wines, resveratrol, and heart health”, Journal of cardiovascular pharmacology, vol. 54, no. 6, pp. 468-476.

7. Biala, A., Tauriainen, E.,Siltanen, A., Shi, J., Merasto, S., Louhelainen, M., Martonen, E., Finckenberg,P., Muller, D.N. & Mervaala, E. 2010, “Resveratrol induces mitochondrial biogenesis and ameliorates Ang II-induced cardiac remodeling in transgenic rats harboring human renin and angiotensinogen genes”, Blood pressure, vol. 19,no. 3, pp. 196-205.

8. Brisdelli, F., D’Andrea, G.& Bozzi, A. 2009, “Resveratrol: A natural polyphenol with multiple chemopreventive properties (Review)”, Current Drug Metabolism, vol. 10, no. 6, pp.530-546.

9. Cacciapuoti, F. 2009,”Opposite effects of metabolic syndrome and calorie restriction on thrombotic disease: Heads and tails of the same coin – Resveratrol’s role”, Metabolic Syndrome and Related Disorders, vol. 7, no. 5, pp. 397-400.

10. Lekli, I., Ray, D. & Das,D.K. 2010, “Longevity nutrients resveratrol, wines and grapes”, Genes and Nutrition, vol.5, no. 1, pp. 55-60.

11. Orallo, F. 2008,”Trans-resveratrol: A magical elixir of eternal youth?”, Current medicinal chemistry, vol.15, no. 19, pp. 1887-1898.

12. Pandey, K.B. & Rizvi, S.I.2010, “Resveratrol may protect plasma proteins from oxidation under conditions of oxidative stress in vitro”, Journal of the Brazilian Chemical Society,vol.21, no. 5, pp. 909-913.

13. Pervaiz, S. & Holme, A.L.2009, “Resveratrol: its biologic targets and functional activity.”, Antioxidants& redox signaling, vol. 11, no. 11, pp. 2851-2897.

14. Shah, P.K. & Patel, J.A.2010, “Resveratrol and its biological actions”, International Journal of Green Pharmacy, vol. 4, no. 1, pp. 15-21.

15. Szekeres, T., Fritzer-Szekeres,M., Saiko, P. & Jäger, W. 2010, “Resveratrol and resveratrol analogues-structure-activity relationship”, Pharmaceutical research, vol. 27, no. 6, pp. 1042-1048.

16. Szkudelska, K. &Szkudelski, T. 2010, “Resveratrol, obesity and diabetes”, European journal of pharmacology, vol. 635, no. 1-3, pp. 1-8.

17. Wojciechowski, P., Louis, X.L.,Thandapilly, S.J., Yu, L. & Netticadan, T. 2010, “Potential of resveratrol in preventing the development of heart failure”, Current Chemical Biology,vol.4, no. 1, pp. 84-88.

Curcumin

18. Bar-Sela, G., Epelbaum, R.& Schaffer, M. 2010, “Curcumin as an anti-cancer agent: Review of the gap between basic and clinical applications”, Current medicinal chemistry,vol.17, no. 3, pp. 190-197.

19. Epstein, J., Sanderson, I.R.& MacDonald, T.T. 2010, “Curcumin as a therapeutic agent: The evidence from in vitro, animal and human studies”, British Journal of Nutrition, vol. 103, no. 11,pp. 1545-1557.

20. Hanai, H. & Sugimoto, K.2009, “Curcumin has bright prospects for the treatment of inflammatory bowel disease”, Current pharmaceutical design, vol. 15, no. 18, pp. 2087-2094.

21. Jurenka, J.S. 2009,”Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: A review of preclinical and clinical research”, Alternative Medicine Review,vol.14, no. 2, pp. 141-153.

22. Kulkarni, S.K., Dhir, A. &Akula, K.K. 2009, “Potentials of curcumin as an antidepressant”, The Scientific World Journal, vol. 9, pp.1233-1241.

22. Shehzad, A. & Lee, Y.S.2010, “Curcumin: Multiple molecular targets mediate multiple pharmacological actions – A review”, Drugs of the Future, vol. 35, no. 2, pp. 113-119

24. Sikora, E., Scapagnini, G.& Barbagallo, M. 2010, “Curcumin, inflammation, ageing and age-related diseases”, Immunity and Ageing, vol. 7.

Green Tea/EGCG

25. Ahmed, S. 2009,”Biological evidence for the benefit of green tea and EGCG in arthritis”, Current Rheumatology Reviews, vol. 5, no. 4, pp. 259-265.

26. Chacko, S.M., Thambi, P.T.,Kuttan, R. & Nishigaki, I. 2010, “Beneficial effects of green tea: A literature review”, Chinese Medicine, vol. 5.

27. Clement, Y. 2009, “Can green tea do that? A literature review of the clinical evidence”, Preventive medicine, vol. 49, no. 2-3, pp. 83-87.

28. Hursel, R., Viechtbauer, W.& Westerterp-Plantenga, M.S. 2009, “The effects of green tea on weight loss and weight maintenance: A meta-analysis”, International journal of obesity,vol. 33,no. 9, pp. 956-961.

29. Moore, R.J., Jackson, K.G.& Minihane, A.M. 2009, “Green tea (Camellia sinensis) catechins and vascular function”, British Journal of Nutrition, vol. 102, no. 12, pp. 1790-1802.

30. Naito, Y. & Yoshikawa, T.2009, “Green tea and heart health”, Journal of cardiovascular pharmacology, vol.54, no. 5, pp. 385-390.

31. Stuart, E.C., Scandlyn, M.J.& Rosengren, R.J. 2006, “Role of epigallocatechin gallate (EGCG) in the treatment of breast and prostate cancer”, Life Sciences, vol. 79, no. 25, pp. 2329-2336.

32. Surh, Y.-. 2006,”NF-κB and AP-1 as molecular targets for chemoprevention with EGCG, a review”, Environmental Chemistry Letters, vol. 4, no. 3, pp. 137-141.

33. Westerterp-Plantenga, M.S.2010, “Green tea catechins, caffeine and body-weight regulation”, Physiology and Behavior, vol.100, no. 1, pp. 42-46.

Nitric Oxide

34. Gkaliagkousi, E., Douma, S.,Zamboulis, C. & Ferro, A. 2009, “Nitric oxide dysfunction in vascular endothelium and platelets: Role in essential hypertension”, Journal of hypertension, vol.27, no. 12, pp. 2310-2320.

35. Schwartz, B.G., Economides, C., Mayeda, G.S., Burstein, S. & Kloner, R.A. 2010, “The endothelial cell in health and disease: its function, dysfunction, measurement and therapy”,International Journal of Impotence Research, vol. 22, no. 2, pp. 77-90.

36. Schini-Kerth, V.B., Auger, C.,Kim, J.-., Étienne-Selloum, N. & Chataigneau, T. 2010, “Nutritional improvement of the endothelial control of vascular tone by polyphenols: role of NO and EDHF”, Pflugers Archiv European Journal of Physiology, , pp. 1-10.

37. Virdis, A., Ghiadoni, L. &Taddei, S. 2010, “Human endothelial dysfunction: EDCFs”, Pflugers Archiv European Journal of Physiology, vol. 459, no. 6, pp. 1015-1023.

38. Crosswhite, P. & Sun, Z.2010, “Nitric oxide, oxidative stress and inflammation in pulmonary arterial hypertension”, Journal of hypertension, vol. 28, no. 2, pp. 201-212.

39. Ferrari, C.K.B., França, E.L.& Honorio-França, A.C. 2009, “Nitric oxide, health and disease”, Journal of Applied Biomedicine, vol. 7, no. 4, pp. 163-173.

40. Heffernan, K.S., Fahs, C.A.,Ranadive, S.M. & Patvardhan, E.A. 2010, “Review article: L-arginine as a nutritional prophylaxis against vascular endothelial dysfunction with aging”,Journal of cardiovascular pharmacology and therapeutics, vol. 15, no. 1, pp. 17-23.

41. Kleinbongard, P., Keymel, S.& Kelm, M. 2007, “New functional aspects of the L-arginine-nitric oxide metabolism within the circulating blood”, Thrombosis and haemostasis,vol.98, no. 5, pp. 970-974.

42. Ma, Q., Wang, Z., Zhang, M.,Hu, H., Li, J., Zhang, D., Guo, K. & Sha, H. 2010, “Targeting the L-arginine-nitric oxide pathway for cancer treatment”, Current pharmaceutical design, vol. 16, no. 4, pp. 392-410.

43. Pervin, S., Singh, R. &Chaudhuri, G. 2008, “Nitric oxide, Nω-hydroxy-l-arginine and breast cancer”, Nitric Oxide – Biology and Chemistry, vol. 19, no. 2, pp. 103-106.

44. Pitocco, D., Zaccardi, F., DiStasio, E., Romitelli, F., Santini, S.A., Zuppi, C. & Ghirlanda, G. 2010,”Oxidative stress, nitric oxide, and diabetes”, Review of Diabetic Studies, vol. 7,no. 1, pp. 15-25.

45. Rajapakse, N.W. & Mattson,D.L. 2009, “Role of l-arginine in nitric oxide production in health and hypertension”, Clinical and Experimental Pharmacology and Physiology, vol. 36, no. 3, pp. 249-255.

46. Wu, G., Bazer, F.W., Davis,T.A., Kim, S.W., Li, P., Marc Rhoads, J., Carey Satterfield, M., Smith, S.B.,Spencer, T.E. & Yin, Y. 2009, “Arginine metabolism and nutrition in growth, health and disease”, Amino acids, vol. 37, no. 1, pp. 153-168.

47. Yi, J., Horky, L.L., Friedlich,A.L., Shi, Y., Rogers, J.T. & Huang, X. 2009, “L-Arginine and Alzheimer’s disase”, International Journal of Clinical and Experimental Pathology, vol. 2,no. 3, pp. 211-238.

Phytosomes/Liposomes

48. Bhattacharya, S. 2009,”Phytosomes: The new technology for enhancement of bioavailability of botanicals and nutraceuticals”, International Journal of Health Research, vol. 2,no. 3, pp. 225-232.

49. Di Pierro, F., Menghi, A.B.,Barreca, A., Lucarelli, M. & Calandrelli, A. 2009, “GreenSelect®Phytosome as an adjunct to a low-calorie diet for treatment of obesity: A clinical trial”,Alternative Medicine Review, vol. 14, no. 2, pp. 154-160.

50. Engelmann, B. & Wiedmann, M.K.H. 2010, “Cellular phospholipid uptake: Flexible paths to coregulate the functions of intracellular lipids”, Biochimica et Biophysica Acta -Molecular and Cell Biology of Lipids, vol. 1801, no. 6, pp. 609-616.

51. Kidd, P.M. 2009, “Bioavailability and activity of phytosome complexes from botanical polyphenols: The silymarin, curcumin, green tea, and grape seed extracts”, Alternative MedicineReview, vol. 14,no. 3, pp. 226-246.

52. Lin, Q., Wang, J., Qin, D.& Bergensta?hl, B. 2007, “Influence of amphiphilic structures on the stability of polyphenols with different hydrophobicity”, Science in China, Series B: Chemistry, vol. 50, no. 1, pp. 121-126.

53. Patel, J., Patel, R.,Khambholja, K. & Patel, N. 2009, “An overview of phytosomes as an advanced herbal drug delivery system”, Asian Journal of Pharmaceutical Sciences, vol. 4,no. 6, pp. 363-371.

54. Sangwan, S. & Dureja, H.2009, “Pharmacosomes: A potential alternative to conventional vesicular systems”, Pharmaceutical Technology, vol. 33, no. 6, pp. 62-65.

55. Semalty, A., Semalty, M.,Rawat, B.S., Singh, D. & Rawat, M.S.M. 2009, “Pharmacosomes: The lipid-based new drug delivery system”, Expert Opinion on Drug Delivery, vol. 6, no. 6, pp.599-612.

56. Semalty, A., Semalty, M.,Rawat, M.S.M. & Franceschi, F. 2009, “Supramolecular phospholipids-polyphenolics interactions: The PHYTOSOME® strategy to improve the bioavailability of phytochemicals”, Fitoterapia, .

57. Setchenkov, M.S., Usmanova,S.I., Afanas’eva, Y.G. & Nasibullin, R.S. 2009, “Complexing of somebiologically active molecules with phosphatidylcholine”, Russian Physics Journal, vol.52, no. 4, pp. 417-420.

58. Setchenkov, M.S., Usmanova,S.I., Afanas’eva, Y.G. & Nasibullin, R.S. 2009, “Complexing of some biologically active molecules with phosphatidylcholine”, Russian Physics Journal, ,pp. 1-4.

Fish Oil/Omega-3 Fatty Acids

59. Anand, R.G., Alkadri, M.,Lavie, C.J. & Milani, R.V. 2008, “The role of fish oil in arrhythmia prevention”, Journal of Cardiopulmonary Rehabilitation and Prevention, vol. 28, no. 2, pp. 92-98.

60. Artham, S.M., Lavie, C.J.,Milani, R.V., Anand, R.G., O’Keefe, J.H. & Ventura, H.O. 2008, “Fish oil in primary and secondary cardiovascular prevention”, Ochsner Journal, vol. 8,no. 2, pp. 49-60.

61. De Ley, M., De Vos, R., Hommes,D.W.S. & Tokkers, P. 2007, “Fish oil for induction of remission in ulcerative colitis”, Cochrane Database of Systematic Reviews, , no. 4.

62. Goldberg, R.B. & Sabharwal,A.K. 2008, “Fish oil in the treatment of dyslipidemia”, Current Opinion in Endocrinology, Diabetes and Obesity, vol. 15, no. 2, pp. 167-174.

63. Lavie, C.J., O’Keefe, J.H.,Milani, R.V., Ventura, H.O. & Mehra, M.R. 2009, “New data on the clinical impact of exercise training, fish oils, and statins in heart failure”, Physician and Sports medicine, vol. 37, no. 2, pp. 22-28.

64. León, H., Shibata, M.C.,Sivakumaran, S., Dorgan, M., Chatterley, T. & Tsuyuki, R.T. 2009,”Effect of fish oil on arrhythmias and mortality: Systematic review”, BMJ, vol. 338,no. 7687, pp. 149-151.

65. Massaro, M., Scoditti, E.,Carluccio, M.A., Campana, M.C. & De Caterina, R. 2010, “Omega-3 fatty acids, inflammation and angiogenesis: basic mechanisms behind the cardioprotective effects of fish and fish oils.”, Cellular and molecular biology (Noisy-le-Grand, France), vol. 56, no. 1, pp. 59-82.

66. Massaro, M., Scoditti, E.,Carluccio, M.A., Montinari, M.R. & De Caterina, R. 2007, “Omega-3 fatty acids, inflammation and angiogenesis: Nutrigenomic effects as an explanation for anti-atherogenic and anti-inflammatory effects of fish and fish oils”, Journal of Nutrigenetics and Nutrigenomics, vol. 1, no. 1-2, pp. 4-23.

67. Tang, W.-., Tang, H.-., Yang, L.-., Wang, X.-., Sun, Y.-. & Huang, X.-. 2009, “Effects of fish oil on prevention of cardiovascular events: A systematic review”, Chinese Journal of Evidence-Based Medicine, vol. 9, no. 11, pp. 1200-1206.

68. Tziomalos, K., Athyros, V.G.& Mikhailidis, D.P. 2007, “Fish oils and vascular disease prevention: An update”, Current medicinal chemistry, vol. 14, no. 24, pp. 2622-2628.

69. Rupasinghe, H.P.V., Erkan, N.& Yasmin, A. 2010, “Antioxidant protection of eicosapentaenoic acid and fish oil oxidation by polyphenolic-enriched apple skin extract”, Journal of Agricultural and Food Chemistry, vol. 58, no. 2, pp. 1233-1239.

Milk Thistle/Silymarin

70. “Green tea, vitamins D and B, milk thistle, cranberries, and turmeric top list of ingredients ranked; call for methods issued.”, 2009, Journal of AOAC International, vol. 92, no. 1, pp. 19A-20A.

71. Baluchnejadmojarad, T., Roghani, M. & Mafakheri, M. 2010, “Neuroprotective effect of silymarin in 6-hydroxydopamine hemi-parkinsonian rat: Involvement of estrogen receptors and oxidative stress”, Neuroscience letters.

72. Belitz, A.R. & Sams, C.E. 2007, The effect of water stress on the growth, yield, and flavonolignan content in milk thistle (Silybum marianum).

73. Bhattacharya, S. 2009, “Phytosomes: Emerging strategy in delivery of herbal drugs and nutraceuticals”, Pharma Times, vol. 41, no. 3, pp. 9-12.

74. Bhattacharya, S. 2009, “Phytosomes: The new technology for enhancement of bioavailability of botanicals and nutraceuticals”, International Journal of Health Research, vol. 2, no. 3, pp. 225-232.

75. Cassileth, B. 2008, “Milk thistle.”, Oncology (Williston Park, N.Y.), vol. 22, no. 11, pp. 1319.

76. Colalto, C. 2010, “Herbal interactions on absorption of drugs: Mechanisms of action and clinical risk assessment”, Pharmacological Research, vol. 62, no. 3, pp. 207-227.

77. Fallah Huseini, H., Yazdani, D., Amin, G. & Makkizadeh, M. 2005, “Milk thistle and cancer”, Journal of Medicinal Plants, vol. 4, no. SUPPL. 1, pp. 46-53.

78. Flaig, T.W., Glodé, M., Gustafson, D., Van Bokhoven, A., Tao, Y., Wilson, S., Su, L.-., Li, Y., Harrison, G., Agarwal, R., Crawford, E.D., Lucia, M.S. & Pollak, M. 2010, “A study of high-dose oral silybin-phytosome followed by prostatectomy in patients with localized prostate cancer”, Prostate, vol. 70, no. 8, pp. 848-855.

79. Hashemi, S.J., Hajiani, E. & Sardabi, E.H. 2009, “A placebo-controlled trial of silymarin in patients with nonalcoholic fatty liver disease”, Hepatitis Monthly, vol. 9, no. 4, pp. 265-270.

80. Hoh, C.S.L., Boocock, D.J., Marczylo, T.H., Brown, V.A., Cai, H., Steward, W.P., Berry, D.P. & Gescher, A.J. 2007, “Quantitation of silibinin, a putative cancer chemopreventive agent derived from milk thistle (Silybum marianum), in human plasma by high-performance liquid chromatography and identification of possible metabolites”, Journal of Agricultural and Food Chemistry, vol. 55, no. 7, pp. 2532-2535.

81. Javed, S., Kohli, K. & Ali, M. 2010, “Patented bioavailability enhancement techniques of silymarin”, Recent Patents on Drug Delivery and Formulation, vol. 4, no. 2, pp. 145-152.

82. Kaur, G., Athar, M. & Alam, M.S. 2009, “Dietary supplementation of silymarin protects against chemically induced nephrotoxicity, inflammation and renal tumor promotion response”, Investigational new drugs, , pp. 1-11.

83. Kidd, P. & Head, K. 2005, “A review of the bioavailability and clinical efficacy of milk thistle phytosome: A silybin-phosphatidylcholine complex (Siliphos®)”, Alternative Medicine Review, vol. 10, no. 3, pp. 193-203.

84. Kurkin, V.A., Ryzhov, V.M., Biryukova, O.V., Mel’Nikova, N.B. & Selekhov, V.V. 2009, “Interaction of milk-thistle-fruit flavanonols with Langmuir monolayers of lecithin and bilayers of liposomes”, Pharmaceutical Chemistry Journal, vol. 43, no. 2, pp. 101-109.

85. Lu, P., Mamiya, T., Lu, L., Mouri, A., Niwa, M., Kim, H.-., Zou, L.-., Nagai, T., Yamada, K., Ikejima, T. & Nabeshima, T. 2010, “Silibinin attenuates cognitive deficits and decreases of dopamine and serotonin induced by repeated methamphetamine treatment”, Behavioural brain research, vol. 207, no. 2, pp. 387-393.

86. McCord, A. 2008, “Milk thistle may help improve liver health in people with HIV and hepatitis C.”, Project Inform perspective, , no. 46, pp. 18.

87. Mudit, V. & Katiyar, S.K. 2010, “Molecular mechanisms of inhibition of photocarcinogenesis by silymarin, a phytochemical from milk thistle (Silybum marianum L. Gaertn.) (Review)”, International journal of oncology, vol. 36, no. 5, pp. 1053-1060.

88. Mukherjee, P.K., Venkatesh, M., Maiti, K., Mukherjee, K. & Saha, B.P. 2009, “Value added herbal drug delivery systems – Perspectives and developments”, Indian Journal of Pharmaceutical Education and Research, vol. 43, no. 4, pp. 329-337.

89. Polyak, S.J., Morishima, C., Lohmann, V., Pal, S., Lee, D.Y.W., Liu, Y., Graf, T.N. & Oberlies, N.H. 2010, “Identification of hepatoprotective flavonolignans from silymarin”,Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 13, pp. 5995-5999.

90. Schulz, V. 2009, “”Therapy-resistant” chronic hepatitis C: Intravenous treatment with silibinin from milk thistle significantly lowers viral load”, Zeitschrift fur Phytotherapie, vol. 30, no. 2, pp. 73-74.

91. Shaker, E., Mahmoud, H. & Mnaa, S. 2010, “Silymarin, the antioxidant component and Silybum marianum extracts prevent liver damage”, Food and Chemical Toxicology, vol. 48, no. 3, pp. 803-806.

92. Usman, M., Ahmad, M., Madni, A.U., Akhtar, N., Asghar, W., Akhtar, M., Atif, M. & Qamar-uz-zaman, M. 2009, “In-vivo kinetics of silymarin (Milk Thistle) on healthy male volunteers”, Tropical Journal of Pharmaceutical Research, vol. 8, no. 4, pp. 311-316.

93. Vaknin, Y., Hadas, R., Schafferman, D., Murkhovsky, L. & Bashan, N. 2008, “The potential of milk thistle (Silybum marianum L.), an Israeli native, as a source of edible sprouts rich in antioxidants”, International journal of food sciences and nutrition, vol. 59, no. 4, pp. 339-346.

94. Vessal, G., Akmali, M., Najafi, P., Moein, M.R. & Sagheb, M.M. 2010, “Silymarin and milk thistle extract may prevent the progression of diabetic nephropathy in streptozotocin-induced diabetic rats”, Renal failure, vol. 32, no. 6, pp. 733-739.

95. Wagoner, J., Negash, A., Kane, O.J., Martinez, L.E., Nahmias, Y., Bourne, N., Owen, D.M., Grove, J., Brimacombe, C., McKeating, J.A., Pécheur, E.-., Graf, T.N., Oberlies, N.H., Lohmann, V., Cao, F., Tavis, J.E. & Polyak, S.J. 2010, “Multiple effects of silymarin on the hepatitis C virus lifecycle”, Hepatology, vol. 51, no. 6, pp. 1912-1921.

96. Wang, H.-., Jiang, Y.-., Ping, L.U., Wang, Q. & Ikejima, T. 2010, “An updated review at molecular pharmacological level for the mechanism of anti-tumor, antioxidant and immunoregulatory action of silibinin”, Yaoxue Xuebao, vol. 45, no. 4, pp. 413-421.

97. Wiese, M. 2009, “Milk thistle and silymarin: Clinical practice and application”, Schweizerische Zeitschrift fur Ganzheits Medizin, vol. 21, no. 1, pp. 24-26.

98. Yarnell, E. & Abascal, K. 2010, “Herbal medicine for viral hepatitis”, Alternative and Complementary Therapies, vol. 16, no. 3, pp. 151-157.

Pomegranate/Punicalagins

99. Adhami, V.M., Khan, N. & Mukhtar, H. 2009, “Cancer chemoprevention by pomegranate: laboratory and clinical evidence.”, Nutrition and cancer, vol. 61, no. 6, pp. 811-815.

100. Basu, A. & Penugonda, K. 2009, “Pomegranate juice: a heart-healthy fruit juice.”, Nutrition reviews, vol. 67, no. 1, pp. 49-56.

101. Bell, C. & Hawthorne, S. 2008, “Ellagic acid, pomegranate and prostate cancer – A mini review”, Journal of Pharmacy and Pharmacology, vol. 60, no. 2, pp. 139-144.

102. Ferrari, G., Maresca, P. & Ciccarone, R. 2010, “The application of high hydrostatic pressure for the stabilization of functional foods: Pomegranate juice”, Journal of Food Engineering, .

103. González-Molina, E., Moreno, D.A. & García-Viguera, C. 2009, “A new drink rich in healthy bioactives combining lemon and pomegranate juices”, Food Chemistry, vol. 115, no. 4, pp. 1364-1372.

104. He, L., Xu, H., Liu, X., He, W., Yuan, F., Hou, Z. & Gao, Y. 2010, “Identification of phenolic compounds from pomegranate (Punica granatum L.) seed residues and investigation into their antioxidant capacities by HPLC-ABTS+ assay”, Food Research International, .

105. Horowitz, S. 2006, “The power of the pomegranate: Biblical fruit with medicinal properties”, Alternative and Complementary Therapies, vol. 12, no. 3, pp. 121-126.

106. Jacob, L.M. 2008, “Pomegranate juice as cell regulator”, KIM – Komplementare und Integrative Medizin, Artztezeitschrift fur Naturheilverfahren, vol. 49, no. 2, pp. 16-20.

107. Jacob, L.M. & Klippel, K.F. 2008, “Pomegranate polyphenol against prostate cancer: New perspectives as well as clinical and pre-hospital data about the effect of pomegranate polyphenols”, Deutsche Zeitschrift fur Onkologie, vol. 40, no. 3, pp. 112-119.

108. Jurenka, J. 2008, “Therapeutic applications of pomegranate (Punica granatum L.): A review”, Alternative Medicine Review, vol. 13, no. 2, pp. 128-144.

109. Khan, N. & Mukhtar, H. 2007, “Pomegranate fruit as a lung cancer chemopreventive agent”, Drugs of the Future, vol. 32, no. 6, pp. 549-554.

110. Lansky, E.P. 2006, “Beware of pomegranates bearing 40% ellagic acid”, Journal of Medicinal Food, vol. 9, no. 1, pp. 119-122.

111. Lansky, E.P. & Newman, R.A. 2007, “Punica granatum (pomegranate) and its potential for prevention and treatment of inflammation and cancer”, Journal of ethnopharmacology,vol. 109, no. 2, pp. 177-206.

112. Li, Y., Qi, Y., Huang, T.H.W., Yamahara, J. & Roufogalis, B.D. 2008, “Pomegranate flower: A unique traditional antidiabetic medicine with dual PPAR-α/-γ activator properties”,Diabetes, Obesity and Metabolism, vol. 10, no. 1, pp. 10-17.

113. Mirmiran, P., Fazeli, M.R., Asghari, G., Shafiee, A. & Azizi, F. 2010, “Effect of pomegranate seed oil on hyperlipidaemic subjects: a double-blind placebo-controlled clinical trial”,British Journal of Nutrition, , pp. 1-5.

114. Mohan, M., Waghulde, H. & Kasture, S. 2010, “Effect of pomegranate juice on angiotensin II-induced hypertension in diabetic wistar rats”, Phytotherapy Research, vol. 24, no. SUPPL. 2, pp. S196-S203.

115. Özgüven, A.I., Yilmaz, M. & Yilmaz, C. 2009, The situation of pomegranate and minor mediterranean fruits in Turkey.

116. Panichayupakaranant, P., Tewtrakul, S. & Yuenyongsawad, S. 2010, “Antibacterial, anti-inflammatory and anti-allergic activities of standardised pomegranate rind extract”, Food Chemistry, vol. 123, no. 2, pp. 400-403.

117. Qu, W., Pan, Z. & Ma, H. 2010, “Extraction modeling and activities of antioxidants from pomegranate marc”, Journal of Food Engineering, vol. 99, no. 1, pp. 16-23.

118. Ross, S.M. 2009, “Pomegranate: Its role in cardiovascular health”, Holistic nursing practice, vol. 23, no. 3, pp. 195-197.

119. Sarkhosh, A., Zamani, Z., Fatahi, R., Ghorbani, H. & Hadian, J. 2007, “A review on medicinal characteristics of pomegranate (Punica granatum L.)”, Journal of Medicinal Plants,vol. 6, no. 22, pp. 13-24.

120. Song, B.-., Tran, H.N.A. & Bae, S.-. 2007, “Pomegranate (Punica granatum) as resources of phytoestrogen and anticancer substances”, Korean Journal of Microbiology and Biotechnology, vol. 35, no. 2, pp. 81-87.

121. Sturgeon, S.R. & Ronnenberg, A.G. 2010, “Pomegranate and breast cancer: possible mechanisms of prevention.”, Nutrition reviews, vol. 68, no. 2, pp. 122-128.

122. Syed, D.N., Afaq, F. & Mukhtar, H. 2007, “Pomegranate derived products for cancer chemoprevention”, Seminars in cancer biology, vol. 17, no. 5, pp. 377-385.

123. Yildiz, H., Obuz, E. & Bayraktaroglu, G. 2009, Pomegranate: Its antioxidant activity and its effect on health.

124. Zhang, L., Gao, Y., Zhang, Y., Liu, J. & Yu, J. 2010, “Changes in bioactive compounds and antioxidant activities in pomegranate leaves”, Scientia Horticulturae, vol. 123, no. 4, pp. 543-546.

125. Zhang, L., Yang, X., Zhang, Y., Wang, L. & Zhang, R. 2010, “In vitro antioxidant properties of different parts of pomegranate flowers”, Food and Bioproducts Processing.

126. Gil, M.I., Tomas-Barberan, F.A., Hess-Pierce, B., Holcroft, D.M. & Kader, A.A. 2000, “Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing”, Journal of Agricultural and Food Chemistry, vol. 48, no. 10, pp. 4581-4589.