ANTINEURODEGENERATIVE ACTIVITY OF MICROALGAE DUNALIELLA SALINA IN RATS WITH ALZHEIMER'S DISEASE

Authors

DOI:

https://doi.org/10.22159/ajpcr.2017.v10i1.14419

Abstract

Objective: The present study is aimed to investigate the promising action of Dunaliella salina extract as a natural protector against Alzheimer's disease (AD) and reported to possess a variety of activities, including antioxidant effects due to its ability to create large amount of carotenoids.

Methods: D. salina is a type of halophile green microalgae was used in the present study. 50 male rats were used in this study, where aluminum chloride was orally administered to induce AD in a dose of 100 mg/kg, daily for 6 weeks. Al-intoxicated rats treated orally daily with D. salina ethanolic extract for 6 weeks in a dose of 150 mg/kg b.wt., whereas standard anti-Alzheimer drug donepezil tartrate was administered at the dose of 10 mg/kg b.wt./day for 6 consecutive weeks. The anti-Alzheimer properties of D. salina extract were achieved through measuring the calmodulin (CaM) level, paraoxonase 1 (PON1) activity, the antiapoptotic marker (Bcl2), brain-derived neurotrophic factor (BDNF), the generation of the DNA adducts (8-hydroxy-2-deoxyguanosine [8-OHdG]/2-deoxy guanosine [2-dG]), and alteration in the expression of amyloid precursor protein, β-site APP-cleaving enzyme 1 (BACE1), and β-site APP-cleaving enzyme 2 (BACE2) in AD rats.

Results: The current results demonstrated that supplementation of AD rats with D. salina extract-enhanced CaM level, and increased PON1 activity, upregulated Bcl2 and BDNF, decreased the levels of DNA adducts (8-OHdG/2-dG), and suppressed the alterations of the expression levels of APP, BACE1, and BACE2-m RNAs as compared with those in AD rats.

Conclusion: It could be concluded that the biological activity of D. salina extract might be regulated by 9-cis b-carotene protecting the brain cells from the oxidative stress in AD rats.

Keywords: Dunaliella salina, Calmodulin, Paraoxonase 1, Bcl2, Brain-derived neurotrophic factor, Alzheimer's disease, DNA adduct, Amyloid precursor protein.

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Author Biography

Farouk K El-baz, professor

Plant Biochemistry

References

Kaur K, Kaur R, Kaur M. Recent advances in Alzheimer’s disease: Causes and treatment. Int J Pharm Pharm Sci 2016;8:8-15.

Nunan J, Small DH. Regulation of APP cleavage by alpha-, beta- and gamma-secretases. FEBS Lett 2000;483(1):6-10.

Manczak M, Anekonda TS, Henson ED, Park BS, Quinn J, Reddy PH. Mitochondria are a direct site of A beta accumulation in Alzheimer’s disease neurons: Implications for free radical generation and oxidative damage in disease progression. Hum Mol Genet 2006;15(9):1437-49.

Zhu XW, Raina AK, Lee HG, Casadesus G, Smith MK, Perry G. Oxidative stress signaling in Alzheimer’s disease. Brain Res 2004;1000(1-2):32-9.

Sano M, Ernesto C, Thomas RG, Klauber MR, Schafer K, Grundman M, et al. A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer’s disease. The Alzheimer’s disease cooperative study. N Engl J Med 1997;336(17):1216-22.

Hsu YW, Tsai CF, Chang WH, Ho YC, Chen WK, Lu FJ. Protective effects of Dunaliella salina-a carotenoid-rich alga, against carbon tetrachloride-induced hepatoxicity in mice. Food Chem Toxicol 2008;46(10):3311-7.

Ben-Amotz A. Dunaliella β-carotene: From science to commerce. In Enigmatic Microorganisms and Life in Extreme Environments. The Netherlands: Kluwer; 1999. p. 401-10.

Raja R, Hemaiswarya S, Rengasamy R. Exploitation of Dunaliella for β-carotene production. Appl Microbiol Biotechnol 2007;74:517-23.

Coesel SN, Baumgartner AC, Teles LM, Ramos AA, Henriques NM, Cancela L, et al. Nutrient limitation is the main regulatory factor for carotenoid accumulation and for Psy and Pds steady state transcript levels in Dunaliella salina (Chlorophyta) exposed to high light and salt stress. Mar Biotechnol 2008;10(5):602-11.

Mogedas B, Casal C, Forján E, Vílchez C. Beta-carotene production enhancement by UV-A radiation in Dunaliella bardawil cultivated in laboratory reactors. J Biosci Bioeng 2009;108(1):47-51.

Krishnakumar S, Bai VD, Rajan RA. Evaluation of bioactive metabolites from halophilic microalgae Dunaliella salina by GC - MS analysis. Int J Pharm Pharm Sci 2013;5:296-303.

Martinez G, Cifuentes A, Gonzalez M, Parra O. Effect of salinity on sexual activity of Dunaliella salina (Dunal) Teodoresco, strain CONC- 006. Rev Chil Hist Nat 1995;68:131-8.

Tsai C, Lu F, Hsu Y. Protective effects of Dunaliella salina - A carotenoids-rich alga - against ultraviolet B-induced corneal oxidative damage in mice. Mol Vis 2012;18:1540-7.

Hieber AD, King TJ, Morioka S, Fukushima LH, Franke AA, Bertram JS. Comparative effects of all-trans beta-carotene vs. 9-cis beta-carotene on carcinogen-induced neoplastic transformation and connexin 43 expression in murine 10T1/2 cells and on the differentiation of human keratinocytes. Nutr Cancer 2000;37(2):234-44.

Stanier RY, Kunisawa MM, Cohn- Bazire G. Purification and properties of unicellular blue green algae (order Chroococcales). Bacteriol Rev 1971;35(2):171-205.

Liang H, Ma A, Zhang P, Bi SL, Shi DY. Effect of ethanol extract of alga Laurencia supplementation on DNA oxidation and alkylation damage in mice. Asia Pac J Clin Nutr 2007;16 Suppl 1:164-8.

Kumar V, Bal A, Gill KD. Aluminum-induced oxidative DNA damage recognition and cell cycle disruption in different regions of rat brain. Toxicology 2009;264(3):137-44.

Bihaqi SW, Sharma M, Singh AP, Tiwari M. Neuroprotective role of Convolvulus pluricaulis on aluminium induced neurotoxicity in rat brain. J Ethnopharmacol 2009;124(3):409-15.

Ruperez FJ, Garcia-Martinez D, Baena B, Maeso N, Cifuentes A, Barbas C, et al. Evolution of oxidative stress parameters and response to oral vitamins E and C in streptozotocin-induced diabetic rats. J Pharm Pharmacol 2008;60(7):871-8.

Tsakiris S, Schulpis KH, Marinou K, Behrakis P. Protective effect of L-cysteine and glutathione on the modulated suckling ratbrain Na+, K+-ATPase and Mg2+-ATPase activities induced by the in vitro galactosaemia. Pharmacol Res 2004;49(5):475-9.

Garg UC, Rai N, Singh Y, Dhaunsi GS, Sidhu GS, Ganguly NK, et al. A spectrophotometric method for calmodulin assay. Biotechniques 1988;6(4):294-6.

Barbareschi M, Caffo O, Veronese S, Leek RD, Fina P, Fox S, et al. Bcl-2 and p53 expression in nodenegative breast carcinoma: A study with long-term follow-up. Hum Pathol 1996;27(11):1149-55.

Barakat-Walter I. Brain derived neurotrophic factor like immunore activity is localized mainly in small sensory neurons of rat dorsal root ganglia. J Neurosci Methods 1996;68(2):281-8.

Ahmed HH, Booles HF, Khalil WK, El-Ashmaoui HM, Othman SM.

Possible therapeutic role of Jasonia candicans and Jasonia montana extracts in the regression of Alzheimer’s disease in experimental model. Am J Biochem Biotechnol 2013;9:144-61.

Khalil WK, Booles HF. Protective role of selenium against over- expression of cancer-related apoptotic genes induced by o-cresol in rats. Arh Hig Rada Toksikol 2011;62(2):121-9.

El-Baz FK, Aly HF, Khalil WK, Booles HF, Saad SA. Jatropha curcas repairing effect on adhesion molecules, DNA damage and gene expression alteration in STZ-induced diabetic rats. Int J Pharm Bio Sci 2015;6:B198-214.

Stein TD, Johnson JA. Lack of neurodegeneration in transgenic mice over expressing mutant amyloid precursor protein is associated with increased levels of transthyretin and the activation of cell survival pathways. J Neurosci 2002;22(17):7380-8.

Luo Y, Bolon B, Damore MD, Fitzpatrick D, Liu H, Zhang J, et al. BACE1 (beta-secretase) knockout mice do not acquire compensatory gene expression changes or develop neural lesions over time. Neurobiol Dis 2003;14(1):81-8.

Deng Y, Xu ZF, Liu W, Xu B, Yang HB, Wei YG. Riluzole-triggered GSH synthesis via activation of glutamate transporters to antagonize methylmercury-induced oxidative stress in rat cerebral cortex. Oxid Med Cell Longev 2012;2012:534705.

McLachlan DR, Wong L, Bergeron C, Baimbridge KG. Calmodulin and calbindin D28K in Alzheimer disease. Alzheimer Dis Assoc Disord 1987;1(3):171-9.

O’Day HD, Eshak K, Myred AM. Calmodulin binding proteins and alzheimer’s disease. J Alzheimer’s Dis 2015;46(3):553-69.

Jomova K, Valko M. Importance of iron chelation in free radical induced oxidative stress and human disease. Curr Pharm Des 2011;17(3):3460-73.

Qian ZM, Ke Y. Rethinking the role of ceruloplasmin in brain iron metabolism. Brain Res Brain Res Rev 2001;35(3):287-94. dementia? Ann N Y Acad Sci 2002;977:96-101.

Wehr H, Bednarska-Makaruk M, Graban A, LipczyÅ„ska-Åojkowska W, Rodo M, BochyÅ„ska A. Paraoxonase activity and dementia. J Neurol Sci 2009;283:107-8.

Zengi O, Karakas A, Ergun U, Senes M, Inan L, Yucel D. Urinary 8-hydroxy-2’-deoxyguanosine level and plasma paraoxo-nase 1 activity with Alzheimer’s disease. Clin Chem Lab Med 2011;50(3):529-34.

Bednarska-Makaruk ME, Krzywkowski T, Graban A, LipczyÅ„ska- Åojkowska W, BochyÅ„ska A, Rodo M, et al. Paraoxonase 1 (PON1) gene-108C> T and p.Q192R polymorphisms and arylesterase activity of the enzyme in patients with dementia. Folia Neuropathol

;51(2):111-9.

Cervellati C, Romani A, Bergamini CM, Bosi C, Sanz JM, Passaro A, et al. PON-1 and ferroxidase activities in older patients with mild cognitive impairment, late onset Alzheimer’s disease or vascular dementia. Clin Chem Lab Med 2015;53(7):1049-56.

Aly HF, Metwally FM, Ahmed HH. Neuroprotective effects of dehydroepiandrosterone (DHEA) in rat model of Alzheimer’s disease. Acta Biochim Pol 2011;58(4):513-20.

Johnson VJ, Kim S, Sharma RP. Aluminum maltolate induces apoptosis and necrosis in neuro-2a cells: Potential role for p53 signaling. Toxicol Sci 2005;83(2):329-39.

Takuma K, Matsuo A, Himeno Y, Hoshina Y, Ohno Y, Funatsu Y, et al. 17-β estradiol attenuates hippocampal neuronal loss and cognitive dysfunction induced by chronic restraint stress in ovariectomized rats. Neuroscience 2007;146(1):60-8.

Nagatsu T, Mogi M, Ichinose H, Togari A. Changes in cytokines and neurotrophins in Parkinson’s disease. J Neural Transm 2000;20(60):277-90.

Guix FX, Uribesalgo I, Coma M, Munoz FJ. The physiology and pathophysiology of nitric oxide in the brain. Prog Neurobiol 2005;76(2):126-52.

Dorheim MA, Tracey WR, Pollock JS, Grammas P. Nitric oxide synthase activity is elevated in brain microvessels in Alzheimer’s disease. Biochem Biophys Res Commun 1994;205(1):659-65.

Platt B, Carpenter DO, Büsselberg D, Reyman KG, Riedel G. Aluminum impairs hippocampal long-term potentiation in rats in vitro and in vivo. Exp Neurol 1995;134(1):73-86.

Canales JJ, Corbalan R, Montoliu C, Liansola M, Monfort P, Erceg S, et al. Aluminum impairs the glutamate- nitric oxide cGMP pathway in cultured neurons and in rat brain in vivo molecular mechanisms and implications for neuropathology. J Inorg Biochem

;87(1-2):63-9.

Lüth H, Holzer M, Gartner U, Staufenbiel M, Arendt T. Expression of endothelial and inducible NOS-isoforms is increased in Alzheimer’s disease, in APP23 transgenic mice and after experimental brain lesion in rat: Evidence for an induction by amyloid pathology. Brain Res

;913(1):57-67.

Vassar R, Citron M. A ß-generating enzymes: Recent advances in ß- and γ-secretase research. Neuron 2000;27:419-22.

Xue KX, Wu JZ, Ma GJ, Yuan S, Qin HL. Comparative studies on genotoxicity and antigenotoxicity of natural and synthetic b-carotene stereoisomers. Mutat Res 1998;418(2-3):73-8.

Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Gluss A, et al. Risk factors for lung cancer and for intervention effects in CARET, the beta-carotene and retinol efficacy trial. J Natl Cancer Inst 1998;88(21):1550-9.

Polozza P, Calviello G, Bartoli GM. Prooxidant activity of beta- carotene under 100% oxygen pressures in rat liver microsomes. Free Radic Biol Med 1995;19(6):887-92.

Published

01-01-2017

How to Cite

El-baz, F. K., H. F. Aly, W. K. Khalil, H. F. Booles, and G. H. Ali. “ANTINEURODEGENERATIVE ACTIVITY OF MICROALGAE DUNALIELLA SALINA IN RATS WITH ALZHEIMER’S DISEASE”. Asian Journal of Pharmaceutical and Clinical Research, vol. 10, no. 1, Jan. 2017, pp. 134-9, doi:10.22159/ajpcr.2017.v10i1.14419.

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