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Evidence-Based Complementary and Alternative Medicine
Volume 2015, Article ID 161092, 12 pages
http://dx.doi.org/10.1155/2015/161092
Research Article

Neuroprotective Properties of the Standardized Extract from Camellia sinensis (Green Tea) and Its Main Bioactive Components, Epicatechin and Epigallocatechin Gallate, in the 6-OHDA Model of Parkinson’s Disease

1Faculty of Medicine of the Federal University of Ceará, Rua Nunes de Melo 1127 (Rodolfo Teófilo), 60430-270 Fortaleza, CE, Brazil
2Faculty of Medicine Estácio of Juazeiro do Norte, Avenida Tenente Raimundo Rocha 515 (Cidade Universitária), 63048-080 Juazeiro do Norte, CE, Brazil

Received 7 February 2015; Revised 25 April 2015; Accepted 25 May 2015

Academic Editor: Cheorl-Ho Kim

Copyright © 2015 Natália Bitu Pinto et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. N. T. Zaveri, “Green tea and its polyphenolic catechins: medicinal uses in cancer and noncancer applications,” Life Sciences, vol. 78, no. 18, pp. 2073–2080, 2006. View at Publisher · View at Google Scholar · View at Scopus
  2. D. C. Chu and L. R. Juneja, “General chemical composition of green tea and its infusion,” in Chemistry and Applications of Green Tea, T. Yamamoto, L. R. Juneja, D. C. Chu, and M. Kim, Eds., pp. 13–22, CRC Press, New York, NY, USA, 1997. View at Google Scholar
  3. Z. Y. Wang, S. J. Cheng, Z. C. Zhou et al., “Antimutagenic activity of green tea polyphenols,” Mutation Research, vol. 223, no. 3, pp. 273–285, 1989. View at Publisher · View at Google Scholar · View at Scopus
  4. C. Han, “Screening of anticarcinogenic ingredients in tea polyphenols,” Cancer Letters, vol. 114, no. 1-2, pp. 153–158, 1997. View at Publisher · View at Google Scholar · View at Scopus
  5. Y. H. Cao and R. H. Cao, “Angiogenesis inhibited by drinking tea,” Nature, vol. 398, no. 6726, p. 381, 1999. View at Publisher · View at Google Scholar · View at Scopus
  6. H. Mukhtar and N. Ahmad, “Green tea in chemoprevention of cancer,” Toxicological Sciences, vol. 52, no. 2, pp. 111–117, 1999. View at Publisher · View at Google Scholar · View at Scopus
  7. C. S. Yang, P. Maliakal, and X. Meng, “Inhibition of carcinogenesis by tea,” Annual Review of Pharmacology and Toxicology, vol. 42, pp. 25–54, 2002. View at Publisher · View at Google Scholar · View at Scopus
  8. U. Pfeffer, N. Ferrari, M. Morini, R. Benelli, D. M. Noonan, and A. Albini, “Antiangiogenic activity of chemopreventive drugs,” International Journal of Biological Markers, vol. 18, no. 1, pp. 70–74, 2003. View at Google Scholar · View at Scopus
  9. S. Mandel and M. B. H. Youdim, “Catechin polyphenols: neurodegeneration and neuroprotection in neurodegenerative diseases,” Free Radical Biology and Medicine, vol. 37, no. 3, pp. 304–317, 2004. View at Publisher · View at Google Scholar · View at Scopus
  10. G. L. Tipoe, T.-M. Leung, M.-W. Hung, and M.-L. Fung, “Green tea polyphenols as an anti-oxidant and anti-inflammatory agent for cardiovascular protection,” Cardiovascular and Hematological Disorders—Drug Targets, vol. 7, no. 2, pp. 135–144, 2007. View at Publisher · View at Google Scholar · View at Scopus
  11. M. E. Cavet, K. L. Harrington, T. R. Vollmer, K. W. Ward, and J.-Z. Zhang, “Anti-inflammatory and anti-oxidative effects of the green tea polyphenol epigallocatechin gallate in human corneal epithelial cells,” Molecular Vision, vol. 17, pp. 533–542, 2011. View at Google Scholar · View at Scopus
  12. C. Pryanka, S. Chandra, P. Dey, and S. Bhattacharya, “Evaluation of anti-inflammatory effects of green tea and black tea: a comparative in vitro study,” Journal of Advanced Pharmaceutical Technology & Research, vol. 3, no. 2, pp. 136–138, 2012. View at Publisher · View at Google Scholar
  13. M. D. A. Teixeira, C. M. Souza, A. P. F. Menezes et al., “Catechin attenuates behavioral neurotoxicity induced by 6-OHDA in rats,” Pharmacology Biochemistry and Behavior, vol. 110, pp. 1–7, 2013. View at Publisher · View at Google Scholar · View at Scopus
  14. A. Hald and J. Lotharius, “Oxidative stress and inflammation in Parkinson's disease: is there a causal link?” Experimental Neurology, vol. 193, no. 2, pp. 279–290, 2005. View at Publisher · View at Google Scholar · View at Scopus
  15. H. Wilms, L. Zecca, P. Rosenstiel, J. Sievers, G. Deuschl, and R. Lucius, “Inflammation in Parkinson's diseases and other neurodegenerative diseases: cause and therapeutic implications,” Current Pharmaceutical Design, vol. 13, no. 18, pp. 1925–1928, 2007. View at Publisher · View at Google Scholar · View at Scopus
  16. A. Hald, J. van Beek, and J. Lotharius, “Inflammation in Parkinson's disease: causative or epiphenomenal?” Sub-Cellular Biochemistry, vol. 42, pp. 249–279, 2007. View at Google Scholar · View at Scopus
  17. M. F. Beal, “Mitochondria, oxidative damage, and inflammation in Parkinson's disease,” Annals of the New York Academy of Sciences, vol. 991, pp. 120–131, 2003. View at Google Scholar · View at Scopus
  18. R. Lee Mosley, E. J. Benner, I. Kadiu et al., “Neuroinflammation, oxidative stress, and the pathogenesis of Parkinson's disease,” Clinical Neuroscience Research, vol. 6, no. 5, pp. 261–281, 2006. View at Publisher · View at Google Scholar · View at Scopus
  19. E. C. Hirsch and S. Hunot, “Neuroinflammation in Parkinson's disease: a target for neuroprotection?” The Lancet Neurology, vol. 8, no. 4, pp. 382–397, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Phani, J. D. Loike, and S. Przedborskia, “Neurodegeneration and inflammation in Parkinson's disease,” Parkinsonism and Related Disorders, vol. 18, supplement 1, pp. S207–S209, 2012. View at Google Scholar · View at Scopus
  21. K. U. Tufekci, R. Meuwissen, S. Genc, and K. Genc, “Inflammation in parkinson's disease,” Advances in Protein Chemistry and Structural Biology, vol. 88, pp. 69–132, 2012. View at Publisher · View at Google Scholar · View at Scopus
  22. E. C. Hirsch, S. Vyas, and S. Hunot, “Neuroinflammation in Parkinson's disease,” Parkinsonism and Related Disorders, vol. 18, supplement 1, pp. S210–S212, 2012. View at Google Scholar · View at Scopus
  23. E. C. Hirsch, “Does oxidative stress participate in nerve cell death in Parkinson's disease?” European Neurology, vol. 33, supplement 1, pp. 52–59, 1993. View at Publisher · View at Google Scholar · View at Scopus
  24. P. Jenner and C. W. Olanow, “Oxidative stress and the pathogenesis of Parkinson's disease,” Neurology, vol. 47, no. 6, pp. S161–S170, 1996. View at Publisher · View at Google Scholar · View at Scopus
  25. S. Nikam, P. Nikam, S. K. Ahaley, and A. V. Sontakke, “Oxidative stress in Parkinson's disease,” Indian Journal of Clinical Biochemistry, vol. 24, no. 1, pp. 98–101, 2009. View at Publisher · View at Google Scholar · View at Scopus
  26. A. L. Friedlich, M. A. Smith, X. Zhu et al., “Oxidative stresss in Parkinson's disease,” The Open Pathology Journal, vol. 3, pp. 38–42, 2009. View at Google Scholar
  27. A. Federico, E. Cardaioli, P. Da Pozzo, P. Formichi, G. N. Gallus, and E. Radi, “Mitochondria, oxidative stress and neurodegeneration,” Journal of the Neurological Sciences, vol. 322, no. 1-2, pp. 254–262, 2012. View at Publisher · View at Google Scholar · View at Scopus
  28. M. Varçin, E. Bentea, Y. Michotte, and S. Sarre, “Oxidative stress in genetic mouse models of Parkinson's disease,” Oxidative Medicine and Cellular Longevity, vol. 2012, Article ID 624925, 25 pages, 2012. View at Publisher · View at Google Scholar · View at Scopus
  29. S. Chakraborty, J. Bornhorst, T. T. Nguyen, and M. Aschner, “Oxidative stress mechanisms underlying Parkinson's disease-associated neurodegeneration in C. elegans,” International Journal of Molecular Sciences, vol. 14, no. 11, pp. 23103–23128, 2013. View at Publisher · View at Google Scholar · View at Scopus
  30. O. Hwang, “Role of oxidative stress in Parkinson's disease,” Experimental Neurobiology, vol. 22, no. 1, pp. 11–17, 2013. View at Publisher · View at Google Scholar
  31. P. Jenner, “Oxidative stress in Parkinson's disease,” Annals of Neurology, vol. 53, supplement 3, pp. S26–S38, 2003. View at Publisher · View at Google Scholar
  32. T. Pan, J. Jankovic, and W. Le, “Potential therapeutic properties of green tea polyphenols in Parkinson's disease,” Drugs & Aging, vol. 20, no. 10, pp. 711–721, 2003. View at Publisher · View at Google Scholar · View at Scopus
  33. S. Mandel, O. Weinreb, T. Amit, and M. B. H. Youdim, “Cell signaling pathways in the neuroprotective actions of the green tea polyphenol (-)-epigallocatechin-3-gallate: implications for neurodegenerative diseases,” Journal of Neurochemistry, vol. 88, no. 6, pp. 1555–1569, 2004. View at Publisher · View at Google Scholar · View at Scopus
  34. O. Weinreb, S. Mandel, T. Amit, and M. B. H. Youdim, “Neurological mechanisms of green tea polyphenols in Alzheimer's and Parkinson's diseases,” Journal of Nutritional Biochemistry, vol. 15, no. 9, pp. 506–516, 2004. View at Publisher · View at Google Scholar · View at Scopus
  35. M. Roth, B. N. Timmermann, and B. Hagenbuch, “Interactions of green tea catechins with organic anion-transporting polypeptides,” Drug Metabolism and Disposition, vol. 39, no. 5, pp. 920–926, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. S. A. Mandel, O. Weinreb, T. Amit, and M. B. H. Youdim, “Molecular mechanisms of the neuroprotective/neurorescue action of multi-target green tea polyphenols,” Frontiers in Bioscience, vol. 4, no. 2, pp. 581–598, 2012. View at Google Scholar · View at Scopus
  37. G. Nie, Y. Cao, and B. Zhao, “Protective effects of green tea polyphenols and their major component, (−)-epigallocatechin-3-gallate (EGCG), on 6-hydroxydopamine-induced apoptosis in PC12 cells,” Redox Report, vol. 7, no. 3, pp. 171–177, 2002. View at Publisher · View at Google Scholar · View at Scopus
  38. R. R. Hou, J. Z. Chen, H. Chen, X. G. Kang, M. G. Li, and B. R. Wang, “Neuroprotective effects of (−)-epigallocatechin-3-gallate (EGCG) on paraquat-induced apoptosis in PC12 cells,” Cell Biology International, vol. 32, no. 1, pp. 22–30, 2008. View at Publisher · View at Google Scholar · View at Scopus
  39. H. Chen, Y. Zhang, X. Lu, and Z. Qu, “Comparative studies on the physicochemical and antioxidant properties of different tea extracts,” Journal of Food Science and Technology, vol. 49, no. 3, pp. 356–361, 2012. View at Publisher · View at Google Scholar · View at Scopus
  40. H. P. S. Makkar, Quantification of Tannins in Tree and Shrub Foliage: A Laboratory Manual, FAO/IAEA Working Document, IAEA, Vienna, Austria, 2000.
  41. G. Paxinos and C. Watson, The Rat Brain in Stereotaxic Coordinates, Academic Press, San Diego, Calif, USA, 1997.
  42. H. H. Draper and M. Hadley, “[43] Malondialdehyde determination as index of lipid peroxidation,” in Oxygen Radicals in Biological Systems Part B: Oxygen Radicals and Antioxidants, vol. 186 of Methods in Enzymology, pp. 421–431, Elsevier, New York, NY, USA, 1990. View at Publisher · View at Google Scholar
  43. L. C. Green, D. A. Wagner, J. Glogowski, P. L. Skipper, J. S. Wishnok, and S. R. Tannenbaum, “Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids,” Analytical Biochemistry, vol. 126, no. 1, pp. 131–138, 1982. View at Publisher · View at Google Scholar · View at Scopus
  44. Y. Li, H. Zhu, and M. A. Trush, “Detection of mitochondria-derived reactive oxygen species production by the chemilumigenic probes lucigenin and luminol,” Biochimica et Biophysica Acta—General Subjects, vol. 1428, no. 1, pp. 1–12, 1999. View at Publisher · View at Google Scholar · View at Scopus
  45. N. Giladi and Y. Balash, “The clinical approach to gaite disturbances in Parkinson's disease: maintaining independent mobility,” Journal of Neural Transmission, vol. 70, supplement, pp. 327–332, 2006. View at Google Scholar
  46. W.-L. Zhu, H.-S. Shi, Y.-M. Wei et al., “Green tea polyphenols produce antidepressant-like effects in adult mice,” Pharmacological Research, vol. 65, no. 1, pp. 74–80, 2012. View at Publisher · View at Google Scholar · View at Scopus
  47. A. M. Haque, M. Hashimoto, M. Katakura, Y. Tanabe, Y. Hara, and O. Shido, “Long-term administration of green tea catechins improves spatial cognition learning ability in rats,” Journal of Nutrition, vol. 136, no. 4, pp. 1043–1047, 2006. View at Google Scholar · View at Scopus
  48. Y. Levites, M. B. H. Youdim, G. Maor, and S. Mandel, “Attenuation of 6-hydroxydopamine (6-OHDA)-induced nuclear factor-kappaB (NF-κB) activation and cell death by tea extracts in neuronal cultures,” Biochemical Pharmacology, vol. 63, no. 1, pp. 21–29, 2002. View at Publisher · View at Google Scholar · View at Scopus
  49. G. Nie, C. Jin, Y. Cao, S. Shen, and B. Zhao, “Distinct effects of tea catechins on 6-hydroxydopamine-induced apoptosis in PC12 cells,” Archives of Biochemistry and Biophysics, vol. 397, no. 1, pp. 84–90, 2002. View at Publisher · View at Google Scholar · View at Scopus
  50. H. Raza and A. John, “In vitro effects of tea polyphenols on redox metabolism, oxidative stress, and apoptosis in PC12 cells,” Annals of the New York Academy of Sciences, vol. 1138, pp. 358–365, 2008. View at Publisher · View at Google Scholar · View at Scopus
  51. R. Moldzio, K. Radad, C. Krewenka et al., “Effects of epigallocatechin gallate on rotenone-injured murine brain cultures,” Journal of Neural Transmission, vol. 117, no. 1, pp. 5–12, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. K.-K. Tai and D. D. Truong, “(-)-Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, reduces dichlorodiphenyl-trichloroethane (DDT)-induced cell death in dopaminergic SHSY-5Y cells,” Neuroscience Letters, vol. 482, no. 3, pp. 183–187, 2010. View at Publisher · View at Google Scholar · View at Scopus
  53. J. Chao, W. K.-W. Lau, M. J. Huie et al., “A pro-drug of the green tea polyphenol (−)-epigallocatechin-3-gallate (EGCG) prevents differentiated SH-SY5Y cells from toxicity induced by 6-hydroxydopamine,” Neuroscience Letters, vol. 469, no. 3, pp. 360–364, 2010. View at Publisher · View at Google Scholar · View at Scopus
  54. V. López and M. I. Calvo, “White Tea (Camellia sinensis Kuntze) exerts neuroprotection against hydrogen peroxide-induced toxicity in PC12 cells,” Plant Foods for Human Nutrition, vol. 66, no. 1, pp. 22–26, 2011. View at Publisher · View at Google Scholar · View at Scopus
  55. M.-Y. Lee, E. J. Choi, M.-K. Lee, and J.-J. Lee, “Epigallocatechin gallate attenuates L-DOPA-induced apoptosis in rat PC12 cells,” Nutrition Research and Practice, vol. 7, no. 4, pp. 249–255, 2013. View at Publisher · View at Google Scholar · View at Scopus
  56. N. Lorenzen, S. B. Nielsen, Y. Yoshimura et al., “How epigallocatechin gallate can inhibit α-synuclein oligomer toxicity in vitro,” The Journal of Biological Chemistry, vol. 289, no. 31, pp. 21299–21310, 2014. View at Publisher · View at Google Scholar
  57. Y. Levites, O. Weinreb, G. Maor, M. B. H. Youdim, and S. Mandel, “Green tea polyphenol (-)-epigallocatechin-3-gallate prevents N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurodegeneration,” Journal of Neurochemistry, vol. 78, no. 5, pp. 1073–1082, 2001. View at Publisher · View at Google Scholar · View at Scopus
  58. J.-Y. Choi, C.-S. Park, D.-J. Kim et al., “Prevention of nitric oxide-mediated 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Parkinson's disease in mice by tea phenolic epigallocatechin 3-gallate,” NeuroToxicology, vol. 23, no. 3, pp. 367–374, 2002. View at Publisher · View at Google Scholar · View at Scopus
  59. S. Guo, J. Yan, T. Yang, X. Yang, E. Bezard, and B. Zhao, “Protective effects of green tea polyphenols in the 6-OHDA rat model of Parkinson's disease through inhibition of ROS-NO pathway,” Biological Psychiatry, vol. 62, no. 12, pp. 1353–1362, 2007. View at Publisher · View at Google Scholar · View at Scopus
  60. J. S. Kim, J.-M. Kim, O. Jeong-Ja, and B. S. Jeon, “Inhibition of inducible nitric oxide synthase expression and cell death by (−)-epigallocatechin-3-gallate, a green tea catechin, in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease,” Journal of Clinical Neuroscience, vol. 17, no. 9, pp. 1165–1168, 2010. View at Publisher · View at Google Scholar · View at Scopus
  61. J. S. AL-amri, M. M. Hagras, and M. I. Mujallid, “Effect of epigallocatechin-3-gallate on inflammatory mediators release in LPS-induced Parkinson's disease in rats,” Indian Journal of Experimental Biology, vol. 51, no. 5, pp. 357–362, 2013. View at Google Scholar · View at Scopus
  62. N. Salah, N. J. Miller, G. Paganga, L. Tijburg, G. P. Bolwell, and C. Rice-Evans, “Polyphenolic flavanols as scavengers of aqueous phase radicals and as chain-breaking antioxidants,” Archives of Biochemistry and Biophysics, vol. 322, no. 2, pp. 339–346, 1995. View at Publisher · View at Google Scholar · View at Scopus
  63. F. Nanjo, K. Goto, R. Seto, M. Suzuki, M. Sakai, and Y. Hara, “Scavenging effects of tea catechins and their derivatives on 1,1- diphenyl-2-picrylhydrazyl radical,” Free Radical Biology and Medicine, vol. 21, no. 6, pp. 895–902, 1996. View at Publisher · View at Google Scholar · View at Scopus
  64. I. Morel, G. Lescoat, P. Cogrel et al., “Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures,” Biochemical Pharmacology, vol. 45, no. 1, pp. 13–19, 1993. View at Publisher · View at Google Scholar · View at Scopus
  65. B. Frei and J. V. Higdon, “Antioxidant activity of tea polyphenols in vivo: evidence from animal studies,” Journal of Nutrition, vol. 133, no. 10, pp. 3275S–3284S, 2003. View at Google Scholar · View at Scopus
  66. M. Assunção, M. J. Santos-Marques, F. Carvalho, and J. P. Andrade, “Green tea averts age-dependent decline of hippocampal signaling systems related to antioxidant defenses and survival,” Free Radical Biology and Medicine, vol. 48, no. 6, pp. 831–838, 2010. View at Publisher · View at Google Scholar · View at Scopus
  67. S. C. Daubner, T. Le, and S. Wang, “Tyrosine hydroxylase and regulation of dopamine synthesis,” Archives of Biochemistry and Biophysics, vol. 508, no. 1, pp. 1–12, 2011. View at Publisher · View at Google Scholar · View at Scopus
  68. Y. Zhu, J. Zhang, and Y. Zeng, “Overview of tyrosine hydroxylase in Parkinson's disease,” CNS & Neurological Disorders—Drug Targets, vol. 11, no. 4, pp. 350–358, 2012. View at Publisher · View at Google Scholar · View at Scopus
  69. S. Tabrez, N. R. Jabir, S. Shakil et al., “A synopsis on the role of tyrosine hydroxylase in Parkinson's disease,” CNS and Neurological Disorders: Drug Targets, vol. 11, no. 4, pp. 395–409, 2012. View at Publisher · View at Google Scholar · View at Scopus
  70. M. Shimizu, A. Deguchi, A. K. Joe, J. F. Mckoy, H. Moriwaki, and I. B. Weinstein, “EGCG inhibits activation of HER3 and expression of cyclooxygenase-2 in human colon cancer cells,” Journal of Experimental Therapeutics and Oncology, vol. 5, no. 1, pp. 69–78, 2005. View at Google Scholar · View at Scopus
  71. T. Hussain, S. Gupta, V. M. Adhami, and H. Mukhtar, “Green tea constituent epigallocatechin-3-gallate selectively inhibits COX-2 without affecting COX-1 expression in human prostate carcinoma cells,” International Journal of Cancer, vol. 113, no. 4, pp. 660–669, 2005. View at Publisher · View at Google Scholar · View at Scopus
  72. G. Peng, D. A. Dixon, S. J. Muga, T. J. Smith, and M. J. Wargovich, “Green tea polyphenol (–)-epigallocatechin-3-gallate inhibits cyclooxygenase-2 expression in colon carcinogenesis,” Molecular Carcinogenesis, vol. 45, no. 5, pp. 309–319, 2006. View at Publisher · View at Google Scholar · View at Scopus
  73. K. Liu, R. Zhou, B. Wang et al., “Effect of green tea on glucose control and insulin sensitivity: a meta-analysis of 17 randomized controlled trials,” The American Journal of Clinical Nutrition, vol. 98, no. 2, pp. 340–348, 2013. View at Publisher · View at Google Scholar · View at Scopus
  74. P. Teismann and J. B. Schulz, “Cellular pathology of Parkinson's disease: astrocytes, microglia and inflammation,” Cell and Tissue Research, vol. 318, no. 1, pp. 149–161, 2004. View at Publisher · View at Google Scholar · View at Scopus
  75. P. Teismann, K. Tieu, D.-K. Choi et al., “Cyclooxygenase-2 is instrumental in Parkinson's disease neurodegeneration,” Proceedings of the National Academy of Sciences of the United States of America, vol. 100, no. 9, pp. 5473–5478, 2003. View at Publisher · View at Google Scholar · View at Scopus
  76. P. Teismann, M. Vila, D.-K. Choi et al., “COX-2 and neurodegeneration in Parkinson's disease,” Annals of the New York Academy of Sciences, vol. 991, pp. 272–277, 2003. View at Google Scholar · View at Scopus
  77. J. M. Taylor, B. S. Main, and P. J. Crack, “Neuroinflammation and oxidative stress: co-conspirators in the pathology of Parkinson's disease,” Neurochemistry International, vol. 62, no. 5, pp. 803–819, 2013. View at Publisher · View at Google Scholar · View at Scopus
  78. Z. M. Wang, C. L. Tidrick, M. Haque, and D. J. Stuehr, “Green tea polyphenols decrease enzyme activity of nitric oxide synthase,” The FASEB Journal, vol. 27, 790.14, 2013. View at Google Scholar