The genetic models in Drosophila provide a platform to understand the mechanism associated with degenerative diseases. The model for Parkinson's disease (PD) based on normal human alpha-synuclein (αS) expression was used in the present study. The aggregation of αS in brain leads to the formation of Lewy bodies and selective loss of dopaminergic neurons due to oxidative stress. Polyphenols generally have the reduced oral bioavailability, increased metabolic turnover, and lower permeability through the blood brain barrier. In the present study, the effect of synthesized alginate-curcumin nanocomposite was studied on the climbing ability of the PD model flies, lipid peroxidation, and apoptosis in the brain of PD model flies. The alginate-curcumin nanocomposite at final doses of 10？5, 10？3, and 10？1？g/mL was supplemented with diet, and the flies were allowed to feed for 24 days. A significant dose-dependent delay in the loss of climbing ability and reduction in the oxidative stress and apoptosis in the brain of PD model flies were observed. The results suggest that alginate-curcumin nanocomposite is potent in delaying the climbing disability of PD model flies and also reduced the oxidative stress as well as apoptosis in the brain of PD model flies. 1. Introduction Curcumin, a polyphenol extracted from the herb curcuma longa L., has been reported to possess antigenotoxic, anticancer, anti-inflammatory, antioxidant, antitumor, and several other biological as well as pharmacological activities [1, 2]. However, the retention time of the curcumin in body is limited due to its rapid systemic elimination and therefore restricts the therapeutic efficacy of curcumin [3]. In addition to the above properties, it has been reported to slow down the progress of Alzheimer’s disease by reducing amyloid-β [4]. It delayed the onset of kainic acid-induced seizures [5]. Nanotechnology is the powerful tool for creating new objects in nanoscale dimensions having important applications in modern biomedical research [6]. Nowadays, ways to get therapeutic drugs to the central nervous system (CNS) effectively, safely, and conveniently are becoming more important than ever. The biomedical and pharmaceutical applications of nanotechnology have greatly facilitated the diagnosis and treatment of CNS diseases [7]. Nanoparticles can be utilized to maintain drug levels in a therapeutically desirable range with longer half-lives, solubility, stability and permeability [7]. In this context, the alginate-curcumin nanocomposite was synthesized, and its effect was studied on the climbing
References
[1]
A. Shehzad, F. Wahid, and Y. S. Lee, “Curcumin in cancer chemoprevention: molecular targets, pharmacokinetics, bioavailability, and clinical trials,” Archives of Pharmacology, vol. 343, no. 9, pp. 489–499, 2010.
[2]
S. Purkayastha, A. Berliner, S. S. Fernando et al., “Curcumin blocks brain tumor formation,” Brain Research, vol. 1266, pp. 130–138, 2009.
[3]
K.-Y. Yang, L.-C. Lin, T.-Y. Tseng, S.-C. Wang, and T.-H. Tsai, “Oral bioavailability of curcumin in rat and the herbal analysis from Curcuma longa by LC-MS/MS,” Journal of Chromatography B, vol. 853, no. 1-2, pp. 183–189, 2007.
[4]
M. Garcia-Alloza, L. A. Borrelli, A. Rozkalne, B. T. Hyman, and B. J. Bacskai, “Curcumin labels amyloid pathology in vivo, disrupts existing plaques, and partially restores distorted neurites in an Alzheimer mouse model,” Journal of Neurochemistry, vol. 102, no. 4, pp. 1095–1104, 2007.
[5]
Y. Sumanont, Y. Murakami, M. Tohda, O. Vajragupta, H. Watanabe, and K. Matsumoto, “Effects of manganese complexes of curcumin and diacetylcurcumin on kainic acid-induced neurotoxic responses in the rat hippocampus,” Biological and Pharmaceutical Bulletin, vol. 30, no. 9, pp. 1732–1739, 2007.
[6]
W. J. Parak, D. Gerior, T. Pellegrino, et al., “Biological applications of colloidal nanocrystals,” Nanotechnology, vol. 14, pp. R15–R27, 2003.
[7]
H. Yang, “Nanoparticle-mediated brain-specific drug delivery, imaging, and diagnosis,” Pharmaceutical Research, vol. 27, no. 9, pp. 1759–1771, 2010.
[8]
M. B. Feany and W. W. Bender, “A Drosophila model of Parkinson's disease,” Nature, vol. 404, no. 6776, pp. 394–398, 2000.
[9]
J. B. Duffy, “GAL4 system in Drosophila: a fly geneticist's Swiss army knife,” Genesis, vol. 34, no. 1-2, pp. 1–15, 2002.
[10]
Y. H. Siddique, G. Ara, M. Faisal, and M. Afzal, “Protective role of Plumbago zeylanica extract against the toxic effects of ethinylestradiol in the third instar larvae of transgenic Drosophila melanogaster (hsp70-lacZ) Bg9 and cultured human peripheral blood lymphocytes,” Alternate Medicine Studies, vol. 1, pp. 26–29, 2011.
[11]
R. G. Pendleton, F. Parvez, M. Sayed, and R. Hillman, “Effects of pharmacological agents upon a transgenic model of Parkinson's disease in Drosophila melanogaster,” Journal of Pharmacology and Experimental Therapeutics, vol. 300, no. 1, pp. 91–96, 2002.
[12]
Y. H. Siddique, G. Ara, and M. Afzal, “Estimation of lipid peroxidation induced by hydrogen peroxide in cultured human lymphocytes,” Dose-Response, vol. 10, no. 1, pp. 1–10, 2012.
[13]
K. J. Mitchell and B. E. Staveley, “Protocol for the detection and analysis of cell death in the adult Drosophila brain,” Drosophila Information Service, vol. 89, pp. 118–121, 2006.
[14]
R. K. Das, N. Kasoju, and U. Bora, “Encapsulation of curcumin in alginate-chitosan-pluronic composite nanoparticles for delivery to cancer cells,” Nanomedicine, vol. 6, no. 1, pp. 153–160, 2010.
[15]
A. Iwai, “Properties of NACP/α-synuclein and its role in Alzheimer's disease,” Biochimica et Biophysica Acta, vol. 1502, no. 1, pp. 95–109, 2000.
[16]
V. N. Uversky, J. Li, P. Souillac et al., “Biophysical properties of the synucleins and their propensities to fibrillate: inhibition of α-synuclein assembly by β- and γ-synucleins,” Journal of Biological Chemistry, vol. 277, no. 14, pp. 11970–11978, 2002.
[17]
O. M. A. El-Agnaf, S. A. Salem, K. E. Paleologou et al., “Detection of oligomeric forms of α-synuclein protein in human plasma as a potential biomarker for Parkinson's disease,” FASEB Journal, vol. 20, no. 3, pp. 419–425, 2006.
[18]
M. Lorenz, J. Urban, U. Engelhardt, G. Baumann, K. Stangl, and V. Stangl, “Green and black tea are equally potent stimuli of NO production and vasodilation: new insights into tea ingredients involved,” Basic Research in Cardiology, vol. 104, no. 1, pp. 100–110, 2009.
[19]
G. M. Cole, T. Morihara, G. P. Lim, F. Yang, A. Begum, and S. A. Frautschy, “NSAID and antioxidant prevention of Alzheimer's disease: lessons from in vitro and animal models,” Annals of the New York Academy of Sciences, vol. 1035, pp. 68–84, 2004.
[20]
S. A. Frautschy, W. Hu, P. Kim et al., “Phenolic anti-inflammatory antioxidant reversal of Aβ-induced cognitive deficits and neuropathology,” Neurobiology of Aging, vol. 22, no. 6, pp. 993–1005, 2001.
[21]
M. S. Wang, S. Boddapati, S. Emadi, and M. R. Sierks, “Curcumin reduces α-synuclein induced cytotoxicity in Parkinson's disease cell model,” BMC Neuroscience, vol. 11, article 57, 2010.
[22]
T. M. Allen and P. R. Cullis, “Drug delivery systems: entering the main stream,” Science, vol. 303, no. 5665, pp. 1818–1822, 2004.
[23]
W. M. Pardridge, “The blood-brain barrier: bottleneck in brain drug development,” NeuroRx, vol. 2, no. 1, pp. 3–14, 2005.
[24]
V. A. Levin, “Relationship of octanol/water partition coefficient and molecular weight to rat brain capillary permeability,” Journal of Medicinal Chemistry, vol. 23, no. 6, pp. 682–684, 1980.
[25]
A. M. Celotto and M. J. Palladino, “Drosophila: a “model” model system to study neurodegeneration,” Molecular Interventions, vol. 5, no. 5, pp. 292–303, 2005.
[26]
W. Jiang, B. Y. S. Kim, J. T. Rutka, and W. C. W. Chan, “Nanoparticle-mediated cellular response is size-dependent,” Nature Nanotechnology, vol. 3, no. 3, pp. 145–150, 2008.
[27]
R. H. Müller and K. Peters, “Nanosuspensions for the formulation of poorly soluble drugs. I. Preparation by a size-reduction technique,” International Journal of Pharmaceutics, vol. 160, no. 2, pp. 229–237, 1998.
[28]
F. Kesisoglou, S. Panmai, and Y. Wu, “Nanosizing—oral formulation development and biopharmaceutical evaluation,” Advanced Drug Delivery Reviews, vol. 59, no. 7, pp. 631–644, 2007.
[29]
S. E. McNeil, “Nanotechnology for the biologist,” Journal of Leukocyte Biology, vol. 78, no. 3, pp. 585–594, 2005.
[30]
A. J. Lees, J. Hardy, and T. Revesz, “Parkinson's disease,” The Lancet, vol. 373, no. 9680, pp. 2055–2066, 2009.
[31]
J. B. Schulz, “Mechanisms of neurodegeneration in idiopathic Parkinson's disease,” Parkinsonism and Related Disorders, vol. 13, no. 3, pp. S306–S308, 2007.
[32]
M. Farrer, J. Kachergus, L. Forno et al., “Comparsion of kindreds with Parkinsonisms and alpha synuclein genomic multiplication,” Annals of Neurology, vol. 55, no. 2, pp. 174–179, 2004.
[33]
K. A. Conway, J.-C. Rochet, R. M. Bieganski, and J. Lansbury P.T., “Kinetic stabilization of the α-synuclein protofibril by a dopamine-α-synuclein adduct,” Science, vol. 294, no. 5545, pp. 1346–1349, 2001.
[34]
B. I. Giasson, J. E. Duda, I. V. J. Murray et al., “Oxidative damage linked to neurodegeneration by selective α-synuclein nitration in synucleinopathy lesions,” Science, vol. 290, no. 5493, pp. 985–989, 2000.
[35]
H. Fujiwara, M. Hasegawa, N. Dohmae et al., “α-synuclein is phosphorylated in synucleinopathy lesions,” Nature Cell Biology, vol. 4, no. 2, pp. 160–164, 2002.
[36]
J. E. Galvin, B. Giasson, H. I. Hurtig, V. M.-Y. Lee, and J. Q. Trojanowski, “Neurodegeneration with brain iron accumulation, type 1 is characterized by α-, β-, and γ-synuclein neuropathology,” American Journal of Pathology, vol. 157, no. 2, pp. 361–368, 2000.
[37]
R. Sharon, I. Bar-Joseph, M. P. Frosch, D. M. Walsh, J. A. Hamilton, and D. J. Selkoe, “The formation of highly soluble oligomers of α-synuclein is regulated by fatty acids and enhanced in Parkinson's disease,” Neuron, vol. 37, no. 4, pp. 583–595, 2003.
[38]
M. Caruana, T. H？gen, J. Levin, A. Hillmer, A. Giese, and N. Vassallo, “Inhibition and disaggregation of α-synuclein oligomers by natural polyphenolic compounds,” FEBS Letters, vol. 585, no. 8, pp. 1113–1120, 2011.
[39]
M. Naoi and W. Maruyama, “Future of neuroprotection in Parkinson's disease,” Parkinsonism and Related Disorders, vol. 8, no. 2, pp. 139–145, 2001.
[40]
J.-M. Lü, J. Nurko, S. M. Weakley et al., “Molecular mechanisms and clinical applications of nordihydroguaiaretic acid (NDGA) and its derivatives: an update,” Medical Science Monitor, vol. 16, no. 5, pp. RA93–RA100, 2010.
[41]
K. Ono and M. Yamada, “Antioxidant compounds have potent anti-fibrillogenic and fibril-destabilizing effects for α-synuclein fibrils in vitro,” Journal of Neurochemistry, vol. 97, no. 1, pp. 105–115, 2006.
[42]
R. Pal, M. Miranda, and M. Narayan, “Nitrosative stress-induced Parkinsonian Lewy-like aggregates prevented through polyphenolic phytochemical analog intervention,” Biochemical and Biophysical Research Communications, vol. 404, no. 1, pp. 324–329, 2011.
[43]
J. Bieschke, J. Russ, R. P. Friedrich et al., “EGCG remodels mature α-synuclein and amyloid-β fibrils and reduces cellular toxicity,” Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 17, pp. 7710–7715, 2010.
[44]
K. A. Youdim, M. Z. Qaiser, D. J. Begley, C. A. Rice-Evans, and N. J. Abbott, “Flavonoid permeability across an in situ model of the blood-brain barrier,” Free Radical Biology and Medicine, vol. 36, no. 5, pp. 592–604, 2004.
[45]
Y. Zhang, V. L. Dawson, and T. M. Dawson, “Oxidative stress and genetics in the pathogenesis of parkinson's disease,” Neurobiology of Disease, vol. 7, no. 4, pp. 240–250, 2000.
[46]
D. A. Butterfield and J. Kanski, “Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins,” Mechanisms of Ageing and Development, vol. 122, no. 9, pp. 945–962, 2001.
[47]
B. I. Giasson, J. E. Duda, S. M. Quinn, B. Zhang, J. Q. Trojanowski, and V. M.-Y. Lee, “Neuronal α-synucleinopathy with severe movement disorder in mice expressing A53T human α-synuclein,” Neuron, vol. 34, no. 4, pp. 521–533, 2002.
[48]
R. A. Abbott, M. Cox, H. Markus, and A. Tomkins, “Diet, body size and micronutrient status in Parkinson's disease,” European Journal of Clinical Nutrition, vol. 46, no. 12, pp. 879–884, 1992.
[49]
K. N. Prasad, W. C. Cole, and B. Kumar, “Multiple antioxidants in the prevention and treatment of Parkinson's disease,” Journal of the American College of Nutrition, vol. 18, no. 5, pp. 413–423, 1999.
[50]
J. Long, H. Gao, L. Sun, J. Liu, and X. Zhao-Wilson, “Grape extract protects mitochondria from oxidative damage and improves locomotor dysfunction and extends lifespan in a Drosophila parkinson's disease model,” Rejuvenation Research, vol. 12, no. 5, pp. 321–331, 2009.
[51]
Y. H. Siddique, G. Ara, S. Jyoti, and M. Afzal, “The dietary supplementation of nordihydroguaiaretic acid (NDGA) delayed the loss of climbing ability in Drosophila model of Parkinson's disease,” Journal of Dietary Supplements, vol. 9, no. 1, pp. 1–8, 2012.
[52]
Y. H. Siddique, G. Ara, S. Jyoti, and M. Afzal, “Protective effect of curcumin in transgenic Drosophila melanogaster model of Parkinson's disease,” Alternate Medicine Studies, vol. 2, no. e3, pp. 7–9, 2012.
[53]
Y. H. Siddique, G. Ara, S. Jyoti, and M. Afzal, “Effect of capsaicin on the climbing ability in Drosophila model of Parkinson's disease,” American Journal of Drug Discovery and Development, vol. 2, no. 1, pp. 50–54, 2012.
[54]
S. Khan, S. Jyoti, F. Naz, et al., “Effect of L-ascorbic acid on the climbing ability and protein levels in the brain of Drosophila model of Parkinson's disease,” International Journal of Neurosciences, vol. 122, no. 12, pp. 704–709, 2012.
[55]
J. M. Abrams, K. White, L. I. Fessler, and H. Steller, “Programmed cell death during Drosophila embryogenesis,” Development, vol. 117, no. 1, pp. 29–43, 1993.
[56]
M. F. W. Festing, V. Baumans, R. D. Combes et al., “Reducing the use of laboratory animals in biomedical research: problems and possible solutions,” Alternatives to Laboratory Animals, vol. 26, no. 3, pp. 283–301, 1998.
[57]
D. J. Benford, A. B. Hanley, K. Bottrill et al., “Biomarkers as predictive tools in toxicity testing,” Alternatives to Laboratory Animals, vol. 28, no. 1, pp. 119–131, 2000.
[58]
R. B. Mythri and M. M. Srinivas Bharath, “Curcumin: a potential neuroprotective agent in Parkinson's disease,” Current Pharmaceutical Design, vol. 18, no. 1, pp. 91–99, 2012.
