Nutraceutical Beverages - ACS Publications - American Chemical

Chapter 10

Red Berries and Their Health Benefits

Downloaded by PENNSYLVANIA STATE UNIV on July 27, 2012 | http://pubs.acs.org Publication Date: December 1, 2003 | doi: 10.1021/bk-2004-0871.ch010

JoLynne D. Wightman Artemis International, Inc., 9318 Airport Drive, Fort Wayne, IN 46809

Red berry fruits such as elderberry, chokeberry, and bilberry have a rich history in folk medicine; from cold and flu remedies to diuretic and antirheumatic activities. They are emerging as natural alternatives in modern medicine and as their popularity grows the amount of scientific research conducted on these products also increases. Researchers have studied their health effects in several areas including cardiovascular disease, and as anti-ulcer, anti-viral, anti-inflammatory and stress-reducting activities. The studies described here used varying forms of berries. Many studies describe the anthocyanins as the causative agent responsible for a given activity, but in addition to containing high concentrations of anthocyanins these fruits also contain a complex mixture of other flavonoids. Thus, it is difficult to determine if the anthocyanins are solely responsible for their activities or if anthocyanins are working synergistically with otherflavonoidsto cause the activity.

© 2004 American Chemical Society In Nutraceutical Beverages; Shahidi, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2003.

123

124


Introduction Red berries have been used in folk medicine for a number of years and now are emerging as a natural alternative in modern medicine. As their popularity grows the amount of scientific research conducted on these products also increases. The red berries discussed here are elderberry (Sambucus nigra), chokeberry (Aronia melanocarpa), and bilberry (Vaccinium myrtillus). There have been several reviews on bilberry (/), but relatively little information gathered in one place for elderberry and chokeberry. Elderberries have been utilized in European folk medicine as early as 400 BC when Hipprocrates referred to the elder tree as his "medicine chest". Additional early remedies with elderberries include laxative (2), diaphoretic and oral anti-inflammatory (3), stomachic activity (4), diuretic, sudorific and antirheumatic (5), and treatment of bacillary dysentery (6). On the otherhand, Chokeberry is native to the Northeastern United States and used by both early settlers and Native Americans for much of the same. Bilberry anthocyanins have had an anecdotal history for improving night vision as well as aiding in scurvy, urinary complaints and diarrhea (J).

Chemical Composition While each of the three berries possesses a unique chemical composition, they are all high in anthocyanins, polyphenols and flavonoids. Both elderberry and chokeberry contain anthocyanins with the cyanidin aglycone, but with varying sugar substitutions. All three berries contain non-acylated anthocyanins, no organic acids are attached to the sugar moiety (7-9). Elderberry contains cyanidin-3-glucoside, cyanidin-3-sambubioside, cyanidin-3,5-diglucoside, and cyanidin-3-sambubioside-5-glucoside (9,10) while chokeberry contains cyanidin3-galactoside, cyanidin-3-glucoside, cyanidin-3-arabinoside, and cyanidin-3xyloside (11,12). Bilberry is reported to contain 15 anthocyanins comprised of five of the six anthocyanin aglycones found in nature (cyanidin, peonidin, delphinidin, petunidin, and malvidin) each with a 3-glucoside, 3-galactoside and 3-arabinoside sugar substitution (8,13). The berries contain differing concentrations of anthocyanins; elderberries, 664-1816 mg anthocyanins/100 g fresh weight (14), chokeberry, 500-1050 mg anthocyanins/100 g, and bilberry, 300-700 mg/100 g (S). Elderberries, chokeberries, and bilberries contain differing flavonoid patterns as well, aside from the anthocyanins. All three contain the flavanols catechin and epicatechin, proanthocyanidins based on these subunits and phenolic acids. Elderberry also contains the flavonol quercetin-3-rutinoside (known as rutin) (9). Chokeberries contain quercetin (known as hyperoside) (15). Bilberries contain the flavonols kaemferol-3-glucoside, quercetin-3glucoside (known as isoquercetrin), quercetin-3-rhamnoside (known as quercitrin), quercetin-3-galactoside and myricetin (9,15). Anthocyanins exist in the berries as glycosides, which were long considered In Nutraceutical Beverages; Shahidi, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2003.

125


non-absorbable into the blood stream. In 1999, Cao and Prior (16) and Miyazawa et al. (17) both reported direct evidence of the absorption of the glycosidic form of elderberry anthocyanins into the human blood stream. Cao and Prior (16) found an anthocyanin concentration of at least 100 μg/L in the plasma, 30 min after the consumption of 1.5 g of elderberry anthocyanins and Miyazawa et al. (17) found 13 μg/L in plasma, 60 min after ingesting 2.95 mg/kg body weight of elderberry and black currant anthocyanins. Additional studies on elderberry anthocyanins have been conducted by Murkovic et al. (18), and Cao et al. (19) confirming these results.

Oxidative and Analgesic Properties Red berries have been shown to be strong antioxidants (20-24). Pool-Zobel et al. (25) reported that both elderberry anthocyanins and anthocyanidins are potent extracellular antioxidants, which may protect cells against external oxidative agents. They found that the anthocyanins are equally or more effective in this activity than the aglycones. Red berry anthocyanins have been reported as analgesic or anti inflammatory agents. Wang et al. (26) showed cyanidin to inhibit both Cox-1 and Cox-2 in vivo. Although this work was done with tart cherries, cyanidin is also the main anthocyanin aglycone found in elderberries and chokeberries. Borrissova et al. (27) reported chokeberry anthocyanins exhibited anti inflammatory activity against histamine- or serotonin-induced inflammation in rats and Rechkemmer and Pool-Zobel (25) reported that chokeberry anthocyanins were able to inhibit insulin-mediated stimulation of metabolism.

Cardiovascular Activities Oxidative modifications of low-density lipoproteins (LDL) are now recognized as one of the major processes in atherogenesis, formations of plaques in the aorta and lesser arteries. Polyphenolics from red berries are among the naturally occurring plant constituents that appear to possess antioxidant activity which act as cardiovascular protection agents (22,28,29). One of the principal causes of plaque formation is the aggregation of oxidized lipoproteins by macrophages, forming foam cells that adhere to arterial walls that induce plaque formation. Mechanisms that would address this problem include the prevention of lipoprotein oxidation and prevention of adhesion of foam cells to arterial walls. Abuja and collaborators (22) reported that anthocyanins from standardized elderberry extract were found to give in vitro antioxidant protection, both from copper-induced LDL oxidation and from the attaché of peroxyl radicals. Laplaud et al. (29) also reported a bilberry extract also exerted potent protective action on LDL's during in vitro copper-mediated oxidation.

In Nutraceutical Beverages; Shahidi, F., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2003.


126 This was shown by prolongation of the lag-phase of conjugated diene production (an indicator of die oxidation of low-density lipoproteins), reduction in lipoperoxides and thiobarbituric acid-reactive substance formation and inhibition of modification in the net negative charge of LDL. In a hamster model Bertuglia et al (28) reported bilberry anthocyanins improved the prevention of adhesion of leukocytes to arterial walls as well as a number of other measures of blood vessel function following induced ischemia and reperfusion. In disease states characterized in part by vascular pathologies (such as atherosclerosis, hypertension and diabetes) endothelium-dependent vasorelaxation in response to different vasodilator agonists is reduced. Vascular endothelium, which lies at the interface between the circulating blood cells and the vascular smooth muscle cells, plays a crucial role in blood flow regulation and vascular tone. Youdim et al (30) reported that in vitro incorporation of standardized elderberry anthocyanins by endothelial cells significantly enhanced their resistance to the damaging effects of oxidative insult. Andriambeloson et al (31) investigated the effects of a red wine polyphenols extract (high in anthocyanins and polyphenols) on rat aortic rings and found that the extract stimulated the vascular endothelial generation of nitric oxide (NO). A mechanism indicated for this effect is a decrease in the endothelial release of nitric oxide (NO). In addition to red wine extract, they investigated the activities of specific anthocyanins and found that those based on delphinidin (found in bilberry), but not malvidin or cyanidin, elicited endothelial-dependent relaxation. They also noted that some flavonoids, including quercetin, cause endotheliumindependent vasorelaxation, perhaps by a direct action on smooth muscle cells. Work previously reported by Bettini et al (cited in (7)) also established that bilberry anthocyanins relaxed vascular smooth muscle. Anthocyanin containing extracts reduced the response to specific contractual agents such as serotonin and acetylcholine. Possible mechanisms put forward for this effect included stimulation of prostacyclin release in vessel walls, stimulation of endotheliumderived relaxing factor and inhibition of catechol-O-methyltransferase. A number of mechanisms may be involved in the effects of anthocyanins on blood vessels which have relevance in such indications as atherosclerosis and other cardiovascular indications, as well as diabetes. According to Morazzoni and Bombardelli (/) the pharmacological results obtained for bilberry anthocyanins justified clinical application for the treatment of blood vessel fragility and altered permeability that occurred with the disease states of hypertension, diabetes and arteriosclerosis. Bilberry extracts have produced positive outcomes in a number of indications; such as improvement of ulcerative dermatitis caused by impaired circulation due to blood clots or varicose veins; reduction in edema in subjects with varicose leg veins; and improvement in capillary-venular microcirculation and lymph drainage. The authors concluded that these results validate pharmacological therapy with anthocyanins for



127 varicose syndrome. Colantuoni et al. (32) examined bilberry anthocyanins in a hamster model and reported that they were effective in promoting and enhancing arteriolar rhythmic diameter changes, which plays a role in the redistribution of microvascular blood flow and interstitial fluid formation. Leitti et al. (33) reported bilberry anthocyanins had significant vasoprotective and antioedema properties in rabbits and rats. Detre et al. (34) found that bilberry anthocyanins increased vascular permeability in the skin and aorta wall more than in brain vessels. They proposed that interaction of collagen in the blood vessel wall, which plays as important role in the control of vascular permeability, with the bilberry anthocyanins may be partly responsible for the protection against the permeability-increasing action of hypertension. Bertuglia et al. (28) reported oral administration of delphinidin (present in bilberry) prevented microangiopathy in experimental diabetes. Alterations in the capillary filtration of macromolecules have been well documented in diabetic patients and experimental diabetes. Cohen-Boulakia et al. (35) reported that bilberry extract was effective in preventing the increase in capillary filtration of albumin and the failure of lymphatic uptake of interstitial albumin in diabetic rats. Human studies have shown that elderberry extract aids in maintaining the triacylglycerol levels in conjunction with a high fat meal. Murkovic et al. (36) found that consumption of elderberry extract with a high fat meal caused no significant increases in postprandial triacylglycerols, whereas consumption of a high fat meal without elderberry extract showed a significant increase in triacylglycerols. In a clinical trial with 105 pregnant women with complications from intrauterine growth retardation (IUGR), Pawlowicz (37) examined the influence of chokeberry anthocyanins on die generation of autoantibodies to oxidized lowdensity lipoproteins. He examined the level of oxidative stress measured by serum concentration of autoantibodies to oxidized low density lipoproteins and concluded that chokeberry anthocyanins were beneficial in controlling oxidative stress during pregnancies complicated by IUGR. Elderberry has been reported to limit some physiological effects of stress. With human subjects, Leitner et al. (38) reported that daily consumption of elderberry concentrates reduced blood glucose levels induced by stress; increased metabolism, which may help to reduce catecholamine levels, and increased cellular oxygen consumption, shown by a lowering of p 0 in spite of faster breathing and high pH; and a drastic decrease in ionized magnesium. 2

Antiulcer and Antiviral Activities Elderberry juice and purified cyanidin-chloride have been shown to have antiulcer activity. In an in vivo mouse model, elderberry juice and elderberry



128 extract were found to have an effective scavenger effect in relation to freeradicals inducing organ lipid peroxidation and the gastric damage induced by HCL/ethanol administration (39). Magistretti et al. (40) examined the antiulcer effects of purified cyanidin-chloride in rat models (cyanidin-based anthocyanins are present in bilberries, elderberries, and chokeberries). They reported that given orally, cyanidin chloride antagonized gastric ulcerations induced by acetic acid, stress, nonsteroidal anti-inflammatory drugs, ethanol, reserpine, histamine and duodenal ulceration inducted by mercaptamine. They suggested that this effect might be due to potentiating die defensive barriers of the gastrointestinal mucosa. In a rat model, administration of chokeberry anthocyanins, prior to the intraperitoneal injections of PAF and ceruleine, were reported to have a beneficial effect on the development of acute experimental pancreatitis (41). Elderberry containsflavonoidswith known antiviral mechanisms, including quercetin, isoquercetin, rutin, and hespiridin (42,43). These constituents can be found in the berries, flowers, and bark of the elder. Wacker and Eilmes (43) reported that incubation of cells with flavonoids for 6-8 h prior to addition of influenza virus protected healthy cells. Anti-viral activity of elderberry has been documented by Zakay-Rones and colleagues (42). Their study had two components: in vitro measurement of the cytopathic effect of the extract on virus replication and agglutination of red blood cells by the extract, and in vivo, a clinical trial of influenza patients. The elderberry extract was shown to be effective in vitro against 10 strains of influenza virus and the clinical trial showed a 3-4 day reduction in flu symptoms due to the elderberry extract. Vivian et al. (44) studied the effect of elderberry extract on cytokine production. They concluded that it activated the healthy immune system by increasing inflammatory cytokine production and proposed that it might be beneficial to the immune system activation and in the inflammatory process in healthy individuals or in patients with various diseases.

Vision Related Activities Morazzoni and Bombardelli (1) compiled clinical studies on the therapeutic uses of bilberry relative to vision. Since various forms of bilberry have been available in Europe for several decades, a vast number of studies dedicated to the use of bilberry in vision related problems have been published there starting in mid-1960. Some of the vision related investigations with bilberry fruit preparations have been on patients with pigmentary retinitis (45) and diabetic retinopathy (46,47), hemeralopia (diminished vision in bright light) (48), macular degeneration, diabetic retinopathy, retinal inflammation, or retinitis pigmentosa (49), progressive myopia (50), various retinopathies (51), myopia, glaucoma, or retinitis pigmentosa (52), diabetic and/or hypertensive retinopathy



129 (53), and polyneuritis due to vascular insufficiency (54); all of which showed improvement when taken in combination with beta-carotene. Possible mechanisms of action for bilberry's effects on ophthalmic conditions include its ability to protect against the breakdown of rhodopsin (retinal purple), a light sensitive pigment located in the rods of the retina, and its ability to regenerate rhodopsin (55). This makes bilberry a possible aid for those with poor night vision (56) or in dim light (57). It may also provide vasoprotection by decreasing capillary fragility and permeability (58,59). In contrast, researchers have also published results refuting the effect of bilberry supplementation on night vision acuity and contrast sensitivity (60). Aside from bilberry's legendary role in improving night vision, it has been used to help in the treatment of glaucoma, cataracts, and retinopathy (61-63). Bilberry anthocyanins can act as antioxidants in the retina of the eye. Retinal protection may be aided by anthocyanidinic retinal phosphoglucomutase and glucose-6-phosphatase inhibition (64). Bilberry has also been shown to strengthen capillaries and reduce hemorrhaging in the retina (65). The anthocyanins may protect both the lens and the retina from oxidative damage.

Anti-cancer Activities Another avenue of research is the use of red berry flavonoids or polyphenolics in anti-cancer activity. Christidou et al. (66) examined standardized chokeberry extracts on malignant human brain tumor cell lines in vitro and found increased cell death and downregulation of MMP-9 secretion. Increased cell death with chokeberry as well as bilberry extracts was also noted. They proposed that chokeberry flavonoids might be promising candidates as novel treatments for brain tumor therapy. Bomser et al. (67) reported that a hexane/chloroform extract of bilberry exhibited potential anticarcinogenic activity as evaluated by in vitro screening tests. Leonardi (68) utilized bilberry extract in the therapeutic treatment offibrocysticmastopathy and reported that therapy for three months in patients with mastodynia, consequent to fibrous mastopathy, was efficacious in reducing symptoms and mammary tension. Red berry products can be found in a variety of forms including: juices, concentrates, powders, fibers, and extracts. These products are all processed differently and thus contain varying amounts of bioactive ingredients. The studies described above used varying forms of the berries. Many studies describe the anthocyanins as the causative agent responsible for a given activity, but thesefruitsare a complex mixture of flavonoids and other compounds. Thus it is difficult, at best, to ascertain if the anthocyanins are solely responsible for the activity or if the anthocyanins are working synergistically with other flavonoids to cause the activity. Therefore it is important for researchers to fully


130 describe the sample they are experimenting with and include any compositional data.


References 1. Morazzoni, P.; Bombardelli, E. Vaccinium myrtillus L. Fitoterapia. 1996, LXVII, 3-28. 2. de Feo, V.; Aquino, R.; Menghini, Α.; Ramundo, E.; Senatore, F. J. Ethnopharmacol. 1992, 36, 113-125. 3. Lokar, L.C.;Poldini, L. J.Ethnopharmacol.1988, 22, 231-278. 4. Novaretti, R.; Lemordant, D. J.Ethnopharmacol.1990, 30, 1-34. 5. Al-Khalili, S. Int. J. Pharmacog. 1995, 33, 317-323. 6. Snajder, K . Sb. Radova. Sapadnika. Inst. Ispitivaye Lekovit Biya (Belgrade). 1951,1,21. 7. Kalt, W.; McDonald, J. E.; Ricker, R. D.; Lu, X . Can. J. Plant Sci. 1999, 79, 617-623. 8. Mazza, G.; Miniati, E. Anthocyanins in Fruits, Vegetables, and Grains. CRC Press: Boca Raton, 1993. 9. Macheix, J.-J.; Fleuriet, Α.; Billot, J. Fruit Phenolics; CRC Press: Boca Raton, FL, 1990. 10. Brønnum-Hansen, Κ.; Hansen, S. H. J. Chromatogr. 1983, 262, 385-392. 11. Oszmianski, J.; Sapis, J.-C. J. Food Sci. 1988, 53, 1241-1242. 12. Strigl, A. W.; Leitner, E.; Pfannhauser, W. Ζ. Lebensm. Unters Forsch. 1995,201,266-268. 13. Baj, Α.; Bombardelli, E.; Babetta, B.; Martinelli, E. M . J. Chromatogr. 1983, 279, 365-372. 14. Kaack, K.; Austed, T. Plant Foods Hum. Nutr. 1998, 52, 187-198. 15. Häkkinen, S. H.; Kärenlampi, S. Ο.; Heinonen, I. M . ; Mykkänen, H. M . ; Törrönen, A. R. J. Agric. Food Chem. 1999, 47, 2274-2279. 16. Cao, G.; Prior, R. L. Clin. Chem. 1999, 45, 574-576. 17. Miyazawa, T.; Nakagawa, K.; Kudo, M . ; Muraishi, K.; Someya, K . J. Agric. Food Chem. 1999, 47, 1083-1091. 18. Murkovic, M . ; Adam, U.; Pfannhauser, W. J. Anal. Chem. 2000, 366, 379381. 19. Cao, G.; Muccitelli, H.; Sanchez-Moreno,C.;Prior, R. L. Am. J. Clin. Nutr. 2001, 73, 920-926. 20. Wang, H.; Cao, G.; Prior, R. L. J. Agric. Food Chem. 1996, 44, 701-705. 21. Satué-Garcia, M . T.; Heinonen, M . ; Frankel, E. J. Agric. Food Chem. 1997, 45, 3362-3367. 22. Abuja, P. M . ; Murkovic, M . ; Pfannhauser, W. J. Agric. Food Chem. 1998, 46, 4091-4096.



131 23. Tsuda, T.; Horia, F.; Osawa, T. FEBS Lett. 1999, 449, 179-182. 24. Salvayre, R.; Braquet, P.; Perruchot, T.; Douste-Blazy, L. Comparison of the scavenger effect of bilberry anthocyanosides with variousflavonoids.In Flavonoids andBioflavonoids,1981; L. Farkas; M . Gábor; F. Kállay and H. Wagner, Eds.; Elsevier Scientific Publishing Company: Amsterdam, 1982; pp 437-442. 25. Pool-Zobel, B. L.; Bub, Α.; Schröder, N.; Rechkemmer, G. Eur. J. Nutr. 1999, 38, 227-234. 26. Wang, H.; Nair, M . G.; Strasburg, G. M.; Booren, A. M . ; Gray, J. I. J. Agric. Food Chem. 1999, 47, 840-844. 27. Borissova, P.; Valcheva, S.; Belcheva, A. Acta Physiol. Pharmacol. Bulg. 1994, 20, 25-30. 28. Bertuglia, S.; Malandrino, S.; Colantuoni, A . Pharmacol. Res. 1995, 31, 183-187. 29. Laplaud, P. M . ; Lelubre, Α.; Chapman, M . J. Fundam. Clin. Pharmacol. 1997, 11, 35-40. 30. Youdim, Κ. Α.; Martin, M.; Joseph, J. A. Free Rad.Biol.Med. 2000, 29, 51-60. 31. Andriambeloson, E.; Magnier, C.; Haan-Archipoff, G. H.; Lobstein, Α.; Anton, R.; Beretz, Α.; Stoclet, J. C.; Andriantsitohaina, R. J. Nutr. 1998, 128, 2324-2333. 32. Colantuoni, Α.; Bertuglia, S.; Magistretti, M . J.; Donato, L. Arzneim. Forsch. 1991, 41, 905-909. 33. Lietti, Α.; Cristoni, Α.; Picci, M . Studies on Vaccinium myrtillus anthocyanosides: vasoprotective and antiinflammatory activity. Arzneim Forsch/Drug Res. 1976, 26, 829-832. 34. Detre, Α.; Jellinek, H.; Miskulin, M.; Robert, A. M . Clin. Physiol. Biochem. 1986, 4, 143-149. 35. Cohen-Boulakia, F.; Valensi, P. E.; Boulahdour, H.; Lestrade, R.; DufourLamartinie, J. F.; Hort-Legrand, C.; Behar, A. Metabolism 2000, 49, 880885. 36. Murkovic, M . ; Toplak, H.; Adam, U.; Pfannhauser, W. J. Food Comp. Anal. 2000, 13, 291-296. 37. Pawlowicz, P.; Wilczynski, J.; Stachowiak, G.; Hincz, P. Gineko.l Pol. 2000, 71, 848-853. 38. Leitner, G.; Westmoreland, D.; Knapp, M . ; Spencer, K.; Merback, J.; Kuzik, V.; Weger, M . ; Pfannhauser, W.; Porta, S. Magnesium-Bulletin 2000, 22, 72-76. 39. Niedworok, J.; Jankowska, B.; Kowalczyk, E.; Charyk, K.; Kubat, Z. Antiulcer activity of anthocyanin from Aronia melanocarpa. Manuscript Lódz, Poland. 40. Magistretti, M . J.; Conti, M.; Cristoni, A. Arzneim -Forsch/Drug Res. 1988, 38, 686-690.



132

21,

41. Jankowski, Α.; Jankowska, Β.; Niedworok, J.Pol.Merkuriusz.Lek.2000, 8, 395-398. 42. Zakay-Rones, Z.; Varsano, N . ; Zlotnik, M . ; Manor, O.; Regev, L.; Schlesinger, M . ; Mumcuoglu, M . J. Alternat. Complimen. Med. 1995, 1, 361-369. 43. Wacker, V . Α.; Eilmes, H.-G. Arzneim -Forsch/Drug Res. 1978, 28, 347350. 44. Barak, V.; Halperin, T.; Kalickman, K. Eur. Cytokine Netw. 2001,12,290. 45. Fiorini, G.; Biancacci, Α.; Graziano, F. M . Ann.Ottalmol.Clin. Ocul. 1965, 91, 371-386. 46. Sevin, R.; Cuendet, J. F. Ophthalmologica 1966,152,109-117. 47. Urso, G. Ann. Ottalmol. Clin. Ocul. 1967, 93, 930-938. 48. Zavarise, G. Ann. Ottalmol. Clin. Ocul. 1968, 94, 209-214. 49. Neumann, L. Klin. Monatsbl. Augenheilkd. 1971,158,592-597. 50. Politzer, M . Klin.Monatsbl.Augenheilkd. 1977,171,616-619. 51. Scharrer, Α.; Ober, M . Klin. Monatsbl. Augenheilkd. 1981,178,368-389. 52. Caselli, L. Arch. Med. Int. (Parma). 1985, 37, 29-35. 53. Perossini, M . ; et.al. Ann. Ottalmol. Clin. Ocul. 1987,113,1173. 54. Pennarola, R.; Roco, P.; Matarazzo, G. Gazz. Med. Ital. 1980, 139, 485491. 55. Alfieri, R.; Sole, P. CR Soc. Biol. 1964, 15, 2338. 56. Sala, D.; Rolando, M . ; Rossi, P. L.; Pissarello, L. Minerva Oftalmol. 1979, 283-285. 57. Jayle, G. E.; Aubert, L.Therapie1964, 19, 171-185. 58. Bone, K.; Morgan, M . Bilberry-The Vision Herb. MediHerb Professional Rev. 1997, 59, 1-4. 59. Regtop, H. Aust. J. Med. Herbalism. 1998, 10, 38-45. 60. Muth, E. R.; Laurent, J.M.;Jasper, P. Altern. Med. Rev. 2000, 5, 164-173. 61. Head, K. A. Altern. Med. Rev. 2001, 6, 144-166. 62. Pizzorno Jr., J. E.; Murray, M . eds. A Text Book of Natural Medicine; Bastyr University Publications: Seattle, WA, 1993. 63. Bravetti, G. Ann. Ottalmol. Clin. Ocul. 1989,115,109. 64. Cluzel, C.; Bastide, P.; Tronche, P. C R Seances Soc. Biol. Fil. 1969, 163, 147-150. 65. Mian, E.; Curri, S. B.; Lietti, Α.; Bombardelli, E. Minerva Med. 1977, 68, 3565-3581. 66. Christidou, Μ. Α.; Rooprai, H. K.; Rucklidge, G. J.; Davis, D.; Clayton, P. R.; Zicha, D.; Pilkington, G. J. The effect of 3 berry flavonoids on malignant human brain tuour cell lines in vitro.; May 27-30: 14th International Conference on Brain Tumor Research and Therapy, 2001. 67. Bomser, J.; Madhavi, D. L.; Singletary, K.; Smith, M . A. L. Planta Med. 1996,62,212-216. 68. Leonardi, M . Minerva Ginecol. 1993, 45, 617-621.


Nutraceutical Beverages - ACS Publications - American Chemical

Recommend Documents