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[1]de Lau, L. M., and M. M. Breteler: Epidemiology of Parkinson’s disease. Lancet Neurol 5(6), 525-535 (2006)
[2]Hoehn, M. M., and M. D. Yahr: Parkinsonism: onset, progression, and mortality. Neurology 50(2), 318-318 (1998)
[3]Pollanen, M. S., D. W. Dickson, and C. Bergeron: Pathology and biology of the Lewy body. J Neuropathol Experi Neurology 52(3), 183-191 (1993)
[4]Nussbaum, R. L., and C. E. Ellis: Alzheimer’s disease and Parkinson’s disease. N Engl J Med 348(14) 1356-1364 (2003)
[5]Ebrahimi, A., and H. Schluesener: Natural polyphenols against neurodegenerative disorders: potentials and pitfalls. Ageing res rev 11(2) 329-345 (2012)
[6]Bhullar, K. S., and H. P. Rupasinghe: Polyphenols: multipotent therapeutic agents in neurodegenerative diseases. Oxi Med Cell Longev 2013 (2013)
[7]Chaumontet, C., V. Bex, I. Gaillard-Sanchez, C. Seillan-Heberden, M. Suschetet, and P. MarTel: Apigenin and tangeretin enhance gap junctional intercellular communication in rat liver epithelial cells. Carcinogenesis 15(10), 2325-2330 (1994)
[8]Datla, K. P., M. Christidou, W. W. Widmer, H. K. Rooprai, and D. T. Dexter: Tissue distribution and neuroprotectiveeffects of citrus flavonoid tangeretin in a rat model of Parkinson’s disease. Neuroreport 12, 3871–3875 (2001)
[9]Seo, J., H. S. Lee, S. Ryoo, J. H. Seo, B. S. Min, and J. H. Lee: Tangeretin, a citrus flavonoid, inhibits PGDF-BB-induced proliferation and migration of aortic smooth muscle cells by blocking AKT activation. Eur J Pharmacol 673,56–64 (2011)
[10]Hirano, T., K. Abe, M. Gotoh, and K. Oka: Citrus flavones tangeretin inhibits leukaemic HL-60 cell growth partially through induction of apoptosis with less cytotoxicity on normal lymphocytes. B J Cancer 72, 1380–1388 (1995)
[11]Lakshmi, A., and S. Subramanian: Chemotherapeutic effect of tangeretin, a polymethoxylated flavone, studied in 7, 12-dimethylbenz (a) anthracene induced mammary carcinoma in experimental rats. Biochimie 99, 96–109 (2014)
[12]Lakshmi, A., and S. P. Subramanian: Tangeretin ameliorates oxidative stress in the renal tissues of rats with experimental breast cancer induced by 7, 12-dimethylbenz (a) anthracene. Toxicol letters 229(2), 333-348 (2014)
[13]Lakshmi, A., and S. Subramanian: Tangeretin, a citrus pentamethoxyflavone, exerts cytostatic effect via p53/p21 upregulation and suppresses metastasis in 7, 12-dimethylbenz(a) anthracene induced rat mammary carcinoma. J Nutri Biochem 25, 1140–1153(2014c)
[14]Xiong, Y., H. Ding, M. Xu, and J. Gao: Protective effects of asiatic acid on rotenone-or H2O2-induced injury in SH-SY5Y cells. Neurochem res 34(4), 746-754 (2009)
[15]Feany, M. B., and W. W. Bender: A Drosophila model of Parkinson’s disease. Nature 404(6776), 394-398 (2000)
[16]Siddique, Y. H., S. Jyoti, and F. Naz: Effect of epicatechin gallate dietary supplementation on transgenic Drosophila model of parkinson’s disease. J diet suppl 11(2), 121-130 (2014)
[17]Siddique, Y. H., G. Ara, S. Jyoti, and M. Afzal: Protective effect of curcumin in transgenic Drosophila melanogaster model of Parkinson’s disease. Alter Med Studies 2(1), 3 (2012)
[18]Pendleton, R. G., F. Parvez, M. Sayed, and R. Hillman: Effects of pharmacological agents upon a transgenic model of Parkinson’s disease in Drosophila melanogaster. J Pharmacol Exp Ther 300(1), 91-96 (2002)
[19]Rosato, E., and C. P. Kyriacou: Analysis of locomotor activity rhythms in Drosophila. Nat Protoc 1(2), 559-568 (2006)
[20]Palladino, M. J., L. P. Keegan, M. A. O’connell, and R. A. Reenan: A-to-I pre-mRNA editing in Drosophila is primarily involved in adult nervous system function and integrity. Cell 102, 437-449 (2000)
[21]Ohkawa, H., O. Nobuko, and K. Yagi: Reaction of linoleic acid hydroperoxide with thiobarbituric acid. J Lipid Res 19, 1053-1057 (1978)
[22]Hawkins, C.L., P.E. Morgan, and M.J. Davies: Quantification of protein modification by oxidants. Free Radic Biol Med 46, 965-988 (2009)
[23]Habig, W.H., M.J. Pabst, G. Fleischner, Z. Gatmaitan, I. M. Arias, and W. B. Jakoby: The Identity of Glutathione S-Transferase B with Ligandin, a Major Binding Protein of Liver. Proc Natl Acad Sci 71, 3879-3882 (1974)
[24]Jollow, D.J., J.R. Mitchell, N. A. Zampaglione, and J. R. Gillette: Bromobenzene-Induced Liver Necrosis. Protective Role of Glutathione and Evidence for 3,4-Bromobenzene Oxide as the Hepatotoxic Metabolite. Pharmacology 11, 151-169 (1974)
[25]Pine L., P.S. Hoffman, G.B. Malcolm, R.F. Benson, and M.G. Keen: Determination of Catalase, Peroxidase, and Superoxide dismutase within the genus Legionella. J Clin Microbiol 20, 421-429(1984)>
[26]Schlumpf, M.,W. Lichtensteiger, H. Langemann, P.G. Waser, and F. Hefti: A fluorometric micromethod forthe simultaneous determination of serotonin, noradrenaline and dopamine inmilligram amounts of brain tissue. Biochem Pharmacol 23, 2437-46 (1974)
[27]Hwang, O: Role of oxidative stress in Parkinson’s disease. Exp neurobiol 22(1), 11-17 (2013)
[28]Jenner, P: Oxidative stress in Parkinson’s disease. Ann neurol 53(S3), S26-S38 (2013)
[29]Recchia, A., P. Debetto, A. Negro, D. Guidolin, S. D. Skaper, and P. Giusti: α-Synuclein and Parkinson’s disease. FASEB J 18(6), 617-626 (2004)
[30]Conway, K. A., J. D. Harper, and P. T. Lansbury: Accelerated in vitro fibril formation by a mutant α-synuclein linked to early-onset Parkinson disease. Nat med 4(11), 1318-1320 (1998)
[31]Giasson, B. I., K. Uryu, J. Q. Trojanowski, and V. M. Y. Lee: Mutant and wild type human α-synucleins assemble into elongated filaments with distinct morphologies in vitro. J Biol Chem 274(12), 7619-7622 (1999)
[32]Lin, Y. P., T. Y. Chen, H. W. Tseng, M. H. Lee, and S. T. Chen: Chemical and biological evaluation of nephrocizin in protecting nerve growth factor-differentiated PC12 cells by 6-hydroxydopamine-induced neurotoxicity. Phytochemistry 84, 102-115 (2012)
[33]Halliwell, B: Reactive oxygen species and the central nervous system. In Free radicals in the brain (pp.21-40) Springer Berlin Heidelberg (1992)
[34]Hertzogi, D. I., and O. Tica: Molecular mechanism underlying the anticancerous action of Flavonoids. Cur Health Sci Journ 38, 145-149 (2012)
[35]Iakovleva, I., A. Begum, M. Pokrzywa, M. Walfridsson, A. E. Sauer-Eriksson, and A. Olofsson: The Flavonoid Luteolin, but Not Luteolin-7-O-Glucoside, Prevents a Transthyretin Mediated Toxic Response. Plos one 1-15 (2015)
[36]Siddique, Y. H., S. Jyoti, F. Naz, and M. Afzal: Protective effect of apigenin in transgenic Drosophila melanogaster model of parkinson’s disease. Pharmacologyonline 3, 790-5 (2011)
[37]Burns, R. S., C. C. Chiueh, S. P. Markey, M. H. Ebert, D. M. Jacobowitz, and I. J. Kopin: A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine. Proc Natl Acad Sci 80(14), 4546-4550 (1983)
[38]Ryter, S.W., H.P. Kim, and A. Hoetzel, J. W. Park, K. Nakahira, X. Wang, and A. M. Choi: Mechanisms of cell death in oxidative stress. Antioxi Redox Signal 9, 49-89 (2007)
[39]Vaca, C.E., J. Wilhelm, and M. Harms-Ringdahl: Interaction of lipid peroxidation products with DNA. A Review. Mutat Res 195, 137-149 (1988)
[40]Dexter, D. T., C. J. Carter, F. R. Wells, F. Javoy-Agid, Y. Agid, A. Lees, P. Jenner and C. D. Marsden: Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease. J Neurochem 52(2), 381-389 (1989)
[41]Dalle-Donne, I., R. Rossi, D. Giustarini, A., Milzani, and R. Colombo: Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta 329, 23-38 (2003)
[42]Alam, Z. I., S. E. Daniel, A. J. Lees, D. C. Marsden, P. Jenner, and B. Halliwell: A generalised increase in protein carbonyls in the brain in Parkinson’s but not incidental Lewy body disease. J Neurochem 69(3), 1326-1329 (1997)
[43]Siddique, Y. H., F. Naz, S. Jyoti, A. Fatima, S. Khanam, F. Ali, S.F. Mujtaba and M. Faisal: Effect of Centella asiatica Leaf Extract on the Dietary Supplementation in Transgenic Drosophila Model of Parkinson’s Disease. Parkinson’s Disease 2014 (2014)
[44]Perry, T. L., D. V. Godin, and S. Hansen: Parkinson’s disease: a disorder due to nigral glutathione deficiency. Neurosci Lett 33(3), 305-310 (1982)
[45]Perry, T. L., and V. W. Yong: Idiopathic Parkinson’s disease, progressive supranuclear palsy and glutathione metabolism in the substantia nigra of patients. Neurosci Lett 67(3), 269-274 (1986)
[46]Pearce, R. K. B., A. Owen, S. Daniel, P. Jenner, and C. D. Marsden: Alterations in the distribution of glutathione in the substantia nigra in Parkinson’s disease. J Neural Transm 104(6-7), 661-677 (1997)
[47]Tipton, K. F., S. Boyce, J. O’Sullivan, G. P. Davey, and J. Healy: Monoamine oxidases: certainties and uncertainties. Curr Med Chem 11(15), 1965-1982 (2004)
[48]Edmondson, D. E., A. Mattevi, C. Binda, M. Li, and F. Hubalek: Structure and mechanism of monoamine oxidase. Burger’s Medicinal Chemistry and Drug Discovery (2003)
[49]Riederer, P., and G. Laux: MAO-inhibitors in Parkinson’s Disease. Exp neurobiol 20(1), 1-17 (2011)
[50]Stuetz, W., T. Prapamontol, S. Hongsibsong, and H. K. Biesalski: Polymethoxylated flavones, flavanone glycosides, carotenoids, and antioxidants in different cultivation types of tangerines (Citrus reticulata Blanco cv. Sainampueng) from Northern Thailand. J Agri Food Chem 58(10), 6069-6074 (2010)
[51]Ho, S. C., and C. C. Lin: Investigation of heat treating conditions for enhancing the anti-inflammatory activity of citrus fruit (Citrus reticulata) peels. J. Agri. Food Chem. 56(17), 7976-7982 (2008)
[52]Horowitz, R. M., and B. Gentili: Flavonoid constituents of citrus. Cit Sci Tech 1(1), 397-426 (1977)
[53]Siems, W., C. Crifo, E. Capuozzo, K. Uchida, T. Grune, and C. Salerno: Metabolism of 4-hydroxy-2-nonenal in human polymorphonuclear leukocytes. Arch Biochem Biophy 503(2), 248-252 (2010)
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Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.
1 Drosophila Transgenic Laboratory, Section of Genetics, Department of Zoology, Faculty of Life Sciences, Aligarh Muslim University, Aligarh, Uttar Pradesh 202002, India
*Author to whom correspondence should be addressed.
Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder caused due to the loss of dopaminergic neurons in substantia nigra region of midbrain. The disease is characterized by the accumulation of alpha-synuclein into depositions known as lewy bodies. Till date there is no cure for PD but the limited number of medications may provide temporary relief from the PD symptoms. Flavonoids are a group of polyphenols found in plants. The health benefits of flavonoids have been universally accepted. Tangeritin is a pentamethoxy flavone found in the peels of Mandarin oranges (Citrus reticulata). The present study was conducted to study the effect of tangeritin on the symptoms of PD exhibited by the PD model transgenic flies (Drosophila melanogaster). Tangeritin at a final concentration of 5, 10 and 20 microM was added to the diet and the flies were allowed to feed on it for 24 days. At the same time other set of PD flies were allowed to feed on a diet having 10-3 M of L-Dopa. The effect of tangeritin was studied on the activity pattern, climbing ability, dopamine content, oxidative stress markers (lipid peroxidation, reduced glutathione, glutathione-S-transferase, protein carbonyl content and monoamine oxidase activity) and on the histopathology of the brain of PD model flies. The study showed that the exposure of PD flies to different doses of tangeritin showed a marked delay in the loss of climbing ability and increase in the dopamine content. Tangeritin also showed a reduction in various oxidative stress markers. Hence it is concluded that tangeritin showed a marked reduction in the PD symptoms and thus could be of great importance for further research in treating PD.
Keywords
- Tangeritin
- Neurodegenerative Disease
- Parkinson’s Disease
- Transgenic Drosophila
References
- [1] de Lau, L. M., and M. M. Breteler: Epidemiology of Parkinson’s disease. Lancet Neurol 5(6), 525-535 (2006)
- [2] Hoehn, M. M., and M. D. Yahr: Parkinsonism: onset, progression, and mortality. Neurology 50(2), 318-318 (1998)
- [3] Pollanen, M. S., D. W. Dickson, and C. Bergeron: Pathology and biology of the Lewy body. J Neuropathol Experi Neurology 52(3), 183-191 (1993)
- [4] Nussbaum, R. L., and C. E. Ellis: Alzheimer’s disease and Parkinson’s disease. N Engl J Med 348(14) 1356-1364 (2003)
- [5] Ebrahimi, A., and H. Schluesener: Natural polyphenols against neurodegenerative disorders: potentials and pitfalls. Ageing res rev 11(2) 329-345 (2012)
- [6] Bhullar, K. S., and H. P. Rupasinghe: Polyphenols: multipotent therapeutic agents in neurodegenerative diseases. Oxi Med Cell Longev 2013 (2013)
- [7] Chaumontet, C., V. Bex, I. Gaillard-Sanchez, C. Seillan-Heberden, M. Suschetet, and P. MarTel: Apigenin and tangeretin enhance gap junctional intercellular communication in rat liver epithelial cells. Carcinogenesis 15(10), 2325-2330 (1994)
- [8] Datla, K. P., M. Christidou, W. W. Widmer, H. K. Rooprai, and D. T. Dexter: Tissue distribution and neuroprotectiveeffects of citrus flavonoid tangeretin in a rat model of Parkinson’s disease. Neuroreport 12, 3871–3875 (2001)
- [9] Seo, J., H. S. Lee, S. Ryoo, J. H. Seo, B. S. Min, and J. H. Lee: Tangeretin, a citrus flavonoid, inhibits PGDF-BB-induced proliferation and migration of aortic smooth muscle cells by blocking AKT activation. Eur J Pharmacol 673,56–64 (2011)
- [10] Hirano, T., K. Abe, M. Gotoh, and K. Oka: Citrus flavones tangeretin inhibits leukaemic HL-60 cell growth partially through induction of apoptosis with less cytotoxicity on normal lymphocytes. B J Cancer 72, 1380–1388 (1995)
- [11] Lakshmi, A., and S. Subramanian: Chemotherapeutic effect of tangeretin, a polymethoxylated flavone, studied in 7, 12-dimethylbenz (a) anthracene induced mammary carcinoma in experimental rats. Biochimie 99, 96–109 (2014)
- [12] Lakshmi, A., and S. P. Subramanian: Tangeretin ameliorates oxidative stress in the renal tissues of rats with experimental breast cancer induced by 7, 12-dimethylbenz (a) anthracene. Toxicol letters 229(2), 333-348 (2014)
- [13] Lakshmi, A., and S. Subramanian: Tangeretin, a citrus pentamethoxyflavone, exerts cytostatic effect via p53/p21 upregulation and suppresses metastasis in 7, 12-dimethylbenz(a) anthracene induced rat mammary carcinoma. J Nutri Biochem 25, 1140–1153(2014c)
- [14] Xiong, Y., H. Ding, M. Xu, and J. Gao: Protective effects of asiatic acid on rotenone-or H2O2-induced injury in SH-SY5Y cells. Neurochem res 34(4), 746-754 (2009)
- [15] Feany, M. B., and W. W. Bender: A Drosophila model of Parkinson’s disease. Nature 404(6776), 394-398 (2000)
- [16] Siddique, Y. H., S. Jyoti, and F. Naz: Effect of epicatechin gallate dietary supplementation on transgenic Drosophila model of parkinson’s disease. J diet suppl 11(2), 121-130 (2014)
- [17] Siddique, Y. H., G. Ara, S. Jyoti, and M. Afzal: Protective effect of curcumin in transgenic Drosophila melanogaster model of Parkinson’s disease. Alter Med Studies 2(1), 3 (2012)
- [18] Pendleton, R. G., F. Parvez, M. Sayed, and R. Hillman: Effects of pharmacological agents upon a transgenic model of Parkinson’s disease in Drosophila melanogaster. J Pharmacol Exp Ther 300(1), 91-96 (2002)
- [19] Rosato, E., and C. P. Kyriacou: Analysis of locomotor activity rhythms in Drosophila. Nat Protoc 1(2), 559-568 (2006)
- [20] Palladino, M. J., L. P. Keegan, M. A. O’connell, and R. A. Reenan: A-to-I pre-mRNA editing in Drosophila is primarily involved in adult nervous system function and integrity. Cell 102, 437-449 (2000)
- [21] Ohkawa, H., O. Nobuko, and K. Yagi: Reaction of linoleic acid hydroperoxide with thiobarbituric acid. J Lipid Res 19, 1053-1057 (1978)
- [22] Hawkins, C.L., P.E. Morgan, and M.J. Davies: Quantification of protein modification by oxidants. Free Radic Biol Med 46, 965-988 (2009)
- [23] Habig, W.H., M.J. Pabst, G. Fleischner, Z. Gatmaitan, I. M. Arias, and W. B. Jakoby: The Identity of Glutathione S-Transferase B with Ligandin, a Major Binding Protein of Liver. Proc Natl Acad Sci 71, 3879-3882 (1974)
- [24] Jollow, D.J., J.R. Mitchell, N. A. Zampaglione, and J. R. Gillette: Bromobenzene-Induced Liver Necrosis. Protective Role of Glutathione and Evidence for 3,4-Bromobenzene Oxide as the Hepatotoxic Metabolite. Pharmacology 11, 151-169 (1974)
- [25] Pine L., P.S. Hoffman, G.B. Malcolm, R.F. Benson, and M.G. Keen: Determination of Catalase, Peroxidase, and Superoxide dismutase within the genus Legionella. J Clin Microbiol 20, 421-429(1984)>
- [26] Schlumpf, M.,W. Lichtensteiger, H. Langemann, P.G. Waser, and F. Hefti: A fluorometric micromethod forthe simultaneous determination of serotonin, noradrenaline and dopamine inmilligram amounts of brain tissue. Biochem Pharmacol 23, 2437-46 (1974)
- [27] Hwang, O: Role of oxidative stress in Parkinson’s disease. Exp neurobiol 22(1), 11-17 (2013)
- [28] Jenner, P: Oxidative stress in Parkinson’s disease. Ann neurol 53(S3), S26-S38 (2013)
- [29] Recchia, A., P. Debetto, A. Negro, D. Guidolin, S. D. Skaper, and P. Giusti: α-Synuclein and Parkinson’s disease. FASEB J 18(6), 617-626 (2004)
- [30] Conway, K. A., J. D. Harper, and P. T. Lansbury: Accelerated in vitro fibril formation by a mutant α-synuclein linked to early-onset Parkinson disease. Nat med 4(11), 1318-1320 (1998)
- [31] Giasson, B. I., K. Uryu, J. Q. Trojanowski, and V. M. Y. Lee: Mutant and wild type human α-synucleins assemble into elongated filaments with distinct morphologies in vitro. J Biol Chem 274(12), 7619-7622 (1999)
- [32] Lin, Y. P., T. Y. Chen, H. W. Tseng, M. H. Lee, and S. T. Chen: Chemical and biological evaluation of nephrocizin in protecting nerve growth factor-differentiated PC12 cells by 6-hydroxydopamine-induced neurotoxicity. Phytochemistry 84, 102-115 (2012)
- [33] Halliwell, B: Reactive oxygen species and the central nervous system. In Free radicals in the brain (pp.21-40) Springer Berlin Heidelberg (1992)
- [34] Hertzogi, D. I., and O. Tica: Molecular mechanism underlying the anticancerous action of Flavonoids. Cur Health Sci Journ 38, 145-149 (2012)
- [35] Iakovleva, I., A. Begum, M. Pokrzywa, M. Walfridsson, A. E. Sauer-Eriksson, and A. Olofsson: The Flavonoid Luteolin, but Not Luteolin-7-O-Glucoside, Prevents a Transthyretin Mediated Toxic Response. Plos one 1-15 (2015)
- [36] Siddique, Y. H., S. Jyoti, F. Naz, and M. Afzal: Protective effect of apigenin in transgenic Drosophila melanogaster model of parkinson’s disease. Pharmacologyonline 3, 790-5 (2011)
- [37] Burns, R. S., C. C. Chiueh, S. P. Markey, M. H. Ebert, D. M. Jacobowitz, and I. J. Kopin: A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine. Proc Natl Acad Sci 80(14), 4546-4550 (1983)
- [38] Ryter, S.W., H.P. Kim, and A. Hoetzel, J. W. Park, K. Nakahira, X. Wang, and A. M. Choi: Mechanisms of cell death in oxidative stress. Antioxi Redox Signal 9, 49-89 (2007)
- [39] Vaca, C.E., J. Wilhelm, and M. Harms-Ringdahl: Interaction of lipid peroxidation products with DNA. A Review. Mutat Res 195, 137-149 (1988)
- [40] Dexter, D. T., C. J. Carter, F. R. Wells, F. Javoy-Agid, Y. Agid, A. Lees, P. Jenner and C. D. Marsden: Basal lipid peroxidation in substantia nigra is increased in Parkinson’s disease. J Neurochem 52(2), 381-389 (1989)
- [41] Dalle-Donne, I., R. Rossi, D. Giustarini, A., Milzani, and R. Colombo: Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta 329, 23-38 (2003)
- [42] Alam, Z. I., S. E. Daniel, A. J. Lees, D. C. Marsden, P. Jenner, and B. Halliwell: A generalised increase in protein carbonyls in the brain in Parkinson’s but not incidental Lewy body disease. J Neurochem 69(3), 1326-1329 (1997)
- [43] Siddique, Y. H., F. Naz, S. Jyoti, A. Fatima, S. Khanam, F. Ali, S.F. Mujtaba and M. Faisal: Effect of Centella asiatica Leaf Extract on the Dietary Supplementation in Transgenic Drosophila Model of Parkinson’s Disease. Parkinson’s Disease 2014 (2014)
- [44] Perry, T. L., D. V. Godin, and S. Hansen: Parkinson’s disease: a disorder due to nigral glutathione deficiency. Neurosci Lett 33(3), 305-310 (1982)
- [45] Perry, T. L., and V. W. Yong: Idiopathic Parkinson’s disease, progressive supranuclear palsy and glutathione metabolism in the substantia nigra of patients. Neurosci Lett 67(3), 269-274 (1986)
- [46] Pearce, R. K. B., A. Owen, S. Daniel, P. Jenner, and C. D. Marsden: Alterations in the distribution of glutathione in the substantia nigra in Parkinson’s disease. J Neural Transm 104(6-7), 661-677 (1997)
- [47] Tipton, K. F., S. Boyce, J. O’Sullivan, G. P. Davey, and J. Healy: Monoamine oxidases: certainties and uncertainties. Curr Med Chem 11(15), 1965-1982 (2004)
- [48] Edmondson, D. E., A. Mattevi, C. Binda, M. Li, and F. Hubalek: Structure and mechanism of monoamine oxidase. Burger’s Medicinal Chemistry and Drug Discovery (2003)
- [49] Riederer, P., and G. Laux: MAO-inhibitors in Parkinson’s Disease. Exp neurobiol 20(1), 1-17 (2011)
- [50] Stuetz, W., T. Prapamontol, S. Hongsibsong, and H. K. Biesalski: Polymethoxylated flavones, flavanone glycosides, carotenoids, and antioxidants in different cultivation types of tangerines (Citrus reticulata Blanco cv. Sainampueng) from Northern Thailand. J Agri Food Chem 58(10), 6069-6074 (2010)
- [51] Ho, S. C., and C. C. Lin: Investigation of heat treating conditions for enhancing the anti-inflammatory activity of citrus fruit (Citrus reticulata) peels. J. Agri. Food Chem. 56(17), 7976-7982 (2008)
- [52] Horowitz, R. M., and B. Gentili: Flavonoid constituents of citrus. Cit Sci Tech 1(1), 397-426 (1977)
- [53] Siems, W., C. Crifo, E. Capuozzo, K. Uchida, T. Grune, and C. Salerno: Metabolism of 4-hydroxy-2-nonenal in human polymorphonuclear leukocytes. Arch Biochem Biophy 503(2), 248-252 (2010)
