7.Ishii S, Koyama T. Soy sauce – old and new panacea seasoning. J Brewing Society of Japan 2004; 99: 218-224.

Green tea

Aiko Iwase

The botanical name of the tea plant is Camellia sinensis. The small-leaf Chinese variety is named Camellia sinensis var. sinensis and the large-leaf black tea discovered in India is named Camellia sinensis var. assamica. In the eighth century, during the Tang Dynasty, Buddhist monks or Japanese envoys are thought to have brought the small-leaf Chinese variety to Japan and thus tea trees cultivated in Japan are Camellia sinensis var. sinensis.1 Green tea produced in Japan is mainly produced by steaming and is unfermented, while oolong tea is half-fermented and black tea is full-fermented. Major chemical components (% of dry weight) of green tea are catechins (9.4-16.2%), theanine (0.5-2.4%), caffeine (2.1-4.0%) and vitamin C (0.1-0.4%).2

Theanine

Theanine is a glutamate analogue. A high concentration of theanine (500 μM) reduced glutamate-induced death of cultured rat cortical neurons, suggesting a neuroprotective effect of on glutamate toxicity.3 In postischemic neuronal death in field CA1 of the gerbil hippocampus, theanine solution given at a dose of 125 and 500 μM significantly suppressed CA1 neuron damage by 60 and 90%, respectively.1 The mechanism of this neuroprotective action may be at least partly attributed to its mild affinity to NMDA and /or AMPA /kainate receptors.4

Since IC50 values for theanine to these receptors are relatively high, other mechanisms, such as effects on the glutamate transporter, were suggested.1 Theanine is absorbed in the intestinal tract, reaching a peak at 0.5-2 hours after oral administration.5,6 A recent study showed that oral intake of l-theanine at a dose of 2 and 4 mg/kg attenuated Abeta(1-42)-induced memory impairment in mice, possibly by suppression of ERK/ P38 and NF-kB, as well as the reduction of oxidative damage.7

Catechins

Catechins are the main bioactive constituents of green tea leaves and consist of eight polyphenolic flavonoid-type compounds; (+)-catechin (C) (-)-epicatechin(EC ), (+)-gallo-catechin(GC), (-)-epigallocatechin(EGC), (+)-gallocatechin(GC), (-)-epigallocatechin(ECG), (+)-gallocatechin gallete(GCG), and (-)-epigallocat- echin gallate(EGCG).8 EGCG is the most abundant of tea catechins and thought to be responsible for the most of biological activity of green tea.9 According to Kuroda and Hara, green tea contains C, EC, ECG, EGC and EGCG at concentrations of 21, 98, 90, 411 and 444 mg/L respectively.10

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Epidemiological studies have suggested potential relationship between green tea drinking and many types of cancer. Further, green tea drinking was reportedly inversely associated with coronary atherosclerosis15 and cerebrovascular diseases.16 However, it must be noted that there are conflicting reports on whether the most effective source of catechins is tea or fruit.17,18

The mechanism of catechin action includes free radical scavenging / antioxidant actions (see reference 2 for review). Among catechins, ECG and EGCG were reported to be the most potent free radical scavengers.19-23 In addition to direct antioxidant effects, catechins also indirectly increase endogenous antioxidative capacity by increasing levels of such enzymes as superoxide dismutase, catalase, glutathione peroxidase and reductase,24 by preventing endogenous antioxidants being depleted by lipid peroxidation,22 or by inhibiting xanthine oxidase.25 EGCG was reported to inhibit many points of apoptotic sequence including caspase 3.26,27 and reportedly modulates the expression of proapoptotic genes such as Bax, while inducing antiapoptotic genes such as BCl-2.28

Because of the above mentioned free radical scavenging, antioxidant, gene modulating activities, together with the ability to cross the blood-brain barrier,29 green tea catechins may potentially act as neuroprotectants in vivo. In fact, epidemiological studies suggest that green tea catechins many reduce the risk for Parkinson’s disease.30,31 Green tea catechins were also reported to protect neuronal death from the Parkinsonian trigger MPTP in animal models.

EGCG also inhibits catechol-O-methyltransferase and may conserve synaptic dopamine in Parkinson’s disease.35 Green tea catechins, especially EGCG, protect the central nervous system in animal models of stroke.36,37 In animal models of Alzheimer’s disease, some green tea catechins specifically bind with and help to clear amyloid-beta.34,38 In cultured hippocampal cells from rat brain, green tea catechins, especially EGCG, at concentration of 5-10 μM, inhibited formation of amyloid-beta fibrils implicated in neuronal death in Alzheimer’s disease.34

Ocular effects of green tea catechins

Oral intake of EGCG (0.4% in drinking water) was reported to attenuate the light-induced photoreceptor damage in albino rats as measured by the a- and b-wave amplitude and expression of various proteins involved in apoptosis such as caspase-3, caspase-8, Bcl-2 and Bad.39 Beneficial effects of oral intake of EGCG (0.5% in drinking water) was also demonstrated in a rat ischemia / reperfusion model, which mainly injures the retinal ganglion cell layer. EGCG siginificantly attenuated the change in a- and b-wave amplitudes, activation of caspases and other ischemia/reperfusion-induced changes in vivo. Further, EGCG inhibited lightinduced apoptosis of cultured RGC-5 cells which was caspase-independent almost completely at 10 μM.40

References

1.Kakuda T. Neuroprotective effects of the green tea components theanine and catechins. Biol Pharm Bull 2002; 25: 1513-1518.

2.Goto T, Yoshida Y, Amano I, Horie H. Chemical composition of commercially available Japanese green tea. Foods Food Ingredients J (Jpn) 1996; 170: 46-51.

3.Nozawa A, Umezawa K, Kobayashi K, et al. Theanine, a major flavorous amino acid in green tea leaves, inhibits glutamate-induced neurotoxicity on cultured rat cerebral cortical neurons (abstract). 1998.

4.Kakuda T, Nozawa A, Sugimoto A, Niino H. Inhibition by theanine of binding of AMPA, kainate, and MDL 105519 to glutamate receptors. Biosci Biotechnol Biochem 2002; 66: 2683-2686.

5.Yokogoshi H, Kabayashi M, Mochizuki M, Terashima T. Effect of theanine, r-glutamyle- thylamide, on brain monoamines and striatal dopamine release in conscious rats. Neurochem Res 1998; 23: 667-673.

6.Unno T, Suzuki Y, Kukuda T, Hayakawa T, Tsuge H. Metabolism of theanine gammaglutamylethlamide in rats. J Agric Food Chem 1999; 47: 1593-1596.

7.Kim TI, Lee YK, Park SG, et al. L-Theanine, an amino acid in green tea, attenuates beta- amyloid-induced cognitive dysfunction and neurotoxicity: reduction in oxidative damage and inactivation of ERK/p38 kinase and NF-KappaB pathways. Free Radic Biol Med 2009; 47: 1601-1610.

8.Sutherland BA, Rahman RM, Appleton I. Mechanism of action of green tea catechins, with a focus on ischemia-induced neurodegeneration. J Nutr Biochem 2006; 17: 291-306.

9.Kimura M, Umegaki K, Kasuya Y, Sugisawa A, Higuchi M. The relation between single/ double or repeated tea catechin ingestions and plasma antioxidant activity in humans. Eur J Clin Nutr 2002; 56: 1186-1193.

10.Kuroda Y, Hara Y. Antimutagenic and anticarcinogenic activity of tea polyphenols. Mutation Res 1999; 436: 69-97.

11.Kohlmeier L, Weterings KG, Steck S, Kok F. Tea and cancer prevention: an evaluation of the epidemiologic literature. Nutr Cancer 1997; 27: 1-13.

12.Chow WH, Blot WJ, McLaughlin J. Tea drinking and cancer risk: epidemiologic evidence. Proc Soc Exp Biol Med 1999; 220: 197.

13.Arab L, Il’yasova D.: The epidemiology of tea consumption and colorectal cancer incidence. J Nutr 2003; 133: 3310S-3318S.

14.Borrelli F, Capasso R, Russo A, Ernst E. Systematic review: green tea and gastrointestinal cancer risk. Aliment Pharmacol Ther 2004; 19: 497-510.

15.Sasazuki S, Kodama H, Yoshimasu K, et al. Relation between green tea consumption and the severity of coronary atherosclerosis among Japanese men and women. Ann Epidemiol 2000 ; 10: 401-408.

16.Sato Y, Nakatsuka H, Watanabe T, et al. Possible contribution of green tea drinking habits to the prevention of stroke. Tohoku J Exp Med 1989; 157: 337-343.

17.Arts IC, Jacobs DR Jr, Harnack LJ, Gross M, Folsom A. Dietary catechins in relation to coronary heart disease death among postmenopausal women. Epidemiology 2001; 12: 668675.

18.Tabak C, Chronic obstructive pulmonary disease and intake of catechins, flavonols, and flavones: the MORGEN Study. Am J Respir Crit Care Med 2001; 164: 61-64.

19.Pannala AS, Rice-Evans CA, Halliwell B, Singh S. Inhibition of peroxynitrite-mediated tyrosine nitration by catechin polyphenols. Biochem Biophys Res Commun 1997; 232: 164168.

20.Nanjo F, Mori M, Goto K, Hara Y. Radical scavenging activity of tea catechins and their related compounds. Biosci Biotechnol Biochem 1999; 63: 1621-1623.

21.Hashimoto R, Yaita M, Tanaka K, Hara Y, Kojo S. Inhibition of radical reaction of apolipoprotein B-100 and alpha-tocopherol in human plasma by green tea catechins. J Agric Food Chem 2000; 48: 6380-6383.

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22.Lotito SB, Fraga C. Catechins delay lipid oxidation and alphatocopherol and beta-carotene depletion following ascorbate depletion in human plasma. Proc Soc Exp Biol Med 2000;

225:32-38.

23.Zhao B, Guo Q, Xin W. Free radical scavenging by green tea polyphenols. Methods Enzymolol 2001; 335: 217-231.

24.Skrzydlewska E, Ostrowska J, Farbiszewski R, Michalak K. Protective effect of green tea against lipid peroxidation in the rat liver, blood serum and the brain. Phytomedicine 2002;

9:232-238.

25.Aucamp J, Gaspar A, Hara Y, Apostolides Z. Inhibition of xanthine Oxidase by catechins from tea (Camellia sinensis). Anticancer Res 1997; 17: 4381-4385.

26.Koh SH, Kim SH, Kwon H, et al. Epigallocatechin gallate protects nerve growth factor differentiated PC12 cells from oxidative-radical-stress-induced apoptosis through its effect on phosphoinositide 3-kinase/Akt and glycogen synthase kinase-3. Brain Res Mol 2003; 118: 72-81.

27.Jeong JH, Kim HJ, Lee TJ, et al. Epigallocatechin 3-gallate attenuates neuronal damage induced by 3-hydroxykynurenine. Toxicology 2004; 195: 53-60.

28.Levites Y, Amit T, Youdim MB, Mandel S. Involvement of protein kinase C activation and cell survival/cell cycle genes in green tea polyphenol (-)-epigallocatechin 3-gallate neuroprotective action. J Biol Chem 2002; 277: 30574-30580.

29.Mandel S, Amit T, Reznichenko L, Weinreb O, Youdim MB. Green tea catechins as brainpermeable, natural iron chelators-antioxidants for the treatment of neurodegenerative disorders. Mol Nutr Food Res 2006; 50: 229-234.

30.Checkoway H, Powers K, Smith-Weller T, et al. Parkinson’s disease risks associated with cigarette smoking, alcohol consumption, and caffeine intake. Am J Epidemiol 2002; 155: 732-738.

31.Tan EK, Tan C, Fook-Chong SM, et al. Dose dependent protective effect of coffee, tea, and smoking in Parkinson’s disease: a study in ethnic Chinese. J Neurol Sci 2003; 216: 163-167.

32.Levites Y, Weinreb O, Maor G, et al. Green tea polyphenol(-)-epigallocatechin-3-gallate prevents N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration. J Neurochem 2001 ; 78: 1073-1082.

33.Mandel SA, Avramovich-Tirosh Y, Reznichenko L, et al. Multifunctional activities of green tea catechins in neuroprotection .Modulation of cell survival genes, iron-dependent oxidative stress and PKC signaling pathway. Neurosignals 2005; 14: 46-60.

34.Bascianetto S, Yao ZX, Papadopoulos V, Quirion R. Neuroprotective effects of green and black teas and their catechin gallate esters against beta-amyloid-induced toxicity. Eur J Neurosci 2006; 23: 55-64.

35.Lu H, Meng X, Yang CS. Enzymology of methylation of tea catechins and inhibirion of catechin-O-methyltransferase by (-)-epigallocatechin gallate. Drug Metab Dispos 2003; 31: 572-579.

36.Lee H, Bae JH, Lee S. Protective effect of green tea polyphenol EGCG against neuronal damage and brain edema after unilateral cerebral ischemia in gerbils. J Neurosci Res 2004;

77:892-900.

37.Sutherland BA, Shaw OM, Clarkson AN, et al. Neuroprotective effects of (-)-epigallocatechin gallate after hypoxia-ischemia-induced brain damage: novel mechanism of action. FASEB J 2005; 19: 258-260.

38.Choi YT, Jung CH, Lee SR, et al. The green tea polyphenol (-)-epigallocatechin gallate attenuates beta-amyloid-induced neurotoxicity in cultures hippocampal neurons. Life Sci 2001; 70: 603-614.

39.Costa BL, Fawcett R, Li GY, Safa R, Osborne NN. Orally administered epigallocatechin gallate attenuates light-induced photoreceptor damage. Brain Res Bull 2008; 76: 412-423.

40.Zhang B, Rusciano D, Osborne NN. Orally administered epigallocatechin gallate attenuates retinal neuronal death in vivo and light-induced apoptosis in vitro. Brain Res 2008; 1198: 141-152.

Non-pharmaceutical approaches to the treatment of glaucoma

Coffee, chocolate, and cocoa

Michael S. Kook

Glial activation and oxidative stress have been increasingly implicated in glaucoma. For instance, unstable ocular blood flow and/or perfusion pressure causing repeated ischemia and reperfusion appears highly relevant in inducing oxidative stress. This in turn may lead to damage to a variety of macromolecules, such as proteins, lipids, sugar residues, or DNA, and thereby to cell death, such as that of retinal ganglion cells. Natural anti-oxidants may thus be important therapeutic modalities.

Coffee beans contain about 8% phenolic compounds, with anti-oxidative effects due to their free radical scavenging and metal-chelating activities. The compound 3-methyl-1,2-cyclopentanedione (MCP), isolated from the coffee extract, is a selective scavenger of peroxynitrite.18 MCP donates a proton to peroxynitrite to neutralize it through the chemical conversion of one of its carbonyl groups, which becomes reduced to a hydroxyl group. Polyphenols in coffee inhibit lipid peroxidation and protect against mutagenicity.19 Despite much debate on the effects of coffee on glaucoma, its antioxidant potential deserves further research.

Chocolate is derived from cocoa beans from the seed of Theobroma cacao.20,21 It contains a class of flavonoids, flavan-3-ols and their oligomers (procyanidins), Dark chocolate generally contains at least twice as much cacao, and thus twice the polyphenols as milk chocolate. In addition, the milk in milk chocolate may reduce absorption of cacao. The anti-oxidative capacity of cacao is higher than that of wine or green tea because of much higher levels of phenolic phytochemicals.22 Several in vivo studies have provided support that the consumption of cacaorich food, such as dark chocolate, is associated with a reduced risk of vascular disease.23,24 The mechanism is due to the action of flavan-3-ols, which augment endothelial NOS, and thereby nitric oxide, to improve endothelium-dependent vasorelaxation.25,26 Ingestion of cacao also decreases both systolic and diastolic blood pressure, improves insulin sensitivity, reduces LDL oxidation susceptibility (thereby increasing the serum total antioxidant capacity and HDL-cholesterol concentrations),27 and reduces platelet adhesiveness and clotting.28,29 Because of these multiple beneficial effects, chocolate also deserves further research and may prove of value in the treatment of glaucoma.

Cocoa pods from the cocoa tree (Theobroma cacao) are harvested and the beans removed and fermented. Dried and roasted beans contain about 300 chemicals, including caffeine, theobromine, and phenethylamine. Chocolate liquor is prepared by finely grinding the nib of the cocoa bean and is the basis for all chocolate products.

Cocoa powder is made by removing part of the cocoa butter from the liquor. Bittersweet chocolate, or dark chocolate, contains at least 15% chocolate liquor but may contain as much as 60%, with the remainder being cocoa butter, sugar, and other additives. Milk chocolate is the predominant form of chocolate

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consumed in the U.S. and typically contains 10-12% chocolate liquor. Therefore, cocoa like dark chocolate contains both a high quantity and quality of phenol antioxidants.30 The consumption of polyphenolic flavonoids from cocoa decreased the risk of heart disease in a cross-cultural epidemiological study.30 This antioxidant activity may exert beneficial effects and may prove valuable in the non-pharmaceutical treatment of glaucoma.27,31

References

1.Claridge KG, Smith SE. Diurnal variation in pulsatile ocular blood flow in normal and glaucomatous eyes. Surv Ophthalmol 1994; 38: S198-205.

2.Harris A, Spaeth G, Wilson R, et al. Nocturnal ophthalmic arterial hemodynamics in primary open-angle glaucoma. J Glaucoma 1997; 6: 170-174.

3.Evans DW, Harris A, Garrett M, Chung HS, Kagemann L. Glaucoma patients demonstrate faulty autoregulation of ocular blood flow during posture change. Br J Ophthalmol 1999;

83:809-813.

4.Osusky R, Rohr P, Schotzau A, Flammer J. Nocturnal dip in the optic nerve head perfusion. Jpn J Ophthalmol 2000; 44: 128-131.

5.Gherghel D, Orgül S, Gugleta K, et al. Retrobulbar blood flow in glaucoma patients with nocturnal over-dipping in systemic blood pressure. Am J Ophthalmol 2001; 132: 641-647.

6.Harris A, Evans D, Martin B, et al. Nocturnal blood pressure reduction: effect on retrobulbar hemodynamics in glaucoma. Graefes Arch Clin Exp Ophthalmol 2002; 240: 372-378.

7.Polska E, Doelemeyer A, Luksch A, et al. Partial antagonism of endothelin 1-induced vasoconstriction in the human choroid by topical unoprostone isopropyl. Arch Ophthalmol 2002;

120:348-352.

8.Sehi M, Flanagan JG, Zeng L, et al. Anterior optic nerve capillary blood flow response to diurnal variation of mean ocular perfusion pressure in early untreated primary open-angle glaucoma. Invest Ophthalmol Vis Sci 2005; 46: 4581-4587.

9.Choi J, Jeong J, Cho HS, et al. Effect of nocturnal blood pressure reduction on circadian fluctuation of mean ocular perfusion pressure: a risk factor fork normal tension glaucoma. Invest Ophthalmol Vis Sci 2006; 47: 831-836.

10.Clifford MN, Knight S, Surucu B, et al. Characterization by LC-MS (n) of four new classes of chlorogenic acids in green coffee beans: dimethoxycinnamoylquinic acids, diferuloyl-quinic acids, caffeoyl-dimethoxycinnamoylquinic acids, and feruloyl-dimethoxycinnamoylquinic acids. J Agric Food Chem 2006; 54: 1957-1969.

11.Galambos P, et al. Compromised autoregulatory control of ocular hemodynamics in glaucoma patients after postural change. Ophthalmology 2006; 113: 1832-1836.

12.Choi J, Kim KH, Jeong J, et al. Circadian fluctuation of mean ocular perfusion pressure is a consistent risk factor for normal-tension glaucoma. Invest Ophthalmol Vis Sci 2007; 48: 104-111.

13.Kim AR, Zou Y, Kim HS et al. Selective peroxynitrite scavenging activity of 3-methyl-1, 2-cyclopentanedione from coffee extract. J Pharm Pharmacol 2002; 54: 1385-1392.

14.Daglia M, Racchi M, Papetty A, et al. In vitro and ex vivo antihydroxy radical activity of green and roasted coffee. J Agric Food Chem 2004; 52: 1700-1704.

15.Wen X, Takenaka M, Murata M et al. Antioxidative activity of a zinc-chelating substance in coffee. Biosci Biotechnol Biochem 2004; 68: 2313-2318.

16.Takenaka M, Sato N, Asakawa H et al. Characterization of a metal-chelating substance in coffee. Biosci Biotechnol Biochem 2005; 69: 26-30.

17.Mozaffarieh M, Grieshaber MC, Orgül S, Flammer J. The potential value of natural antioxidative treatment in glaucoma. Surv Ophthalmol 2008; 53: 479-505.