Generic placeholder image

Current Alzheimer Research

Editor-in-Chief

ISSN (Print): 1567-2050
ISSN (Online): 1875-5828

Research Article

Neuroprotective Effect of Fucoxanthin against Intracerebroventricular Streptozotocin (ICV-STZ) Induced Cognitive Impairment in Experimental Rats

Author(s): Mahadev Dhami, Khadga Raj and Shamsher Singh*

Volume 18, Issue 8, 2021

Page: [623 - 637] Pages: 15

DOI: 10.2174/1567205018666211118144602

Price: $65

Open Access Journals Promotions 2
Abstract

Background: Alzheimer's disease (AD) is a neurological disorder characterized by loss of memory and cognitive functions caused by oxidative stress, neuroinflammation, change in neurotransmitter levels, and excessive deposition of Aβ(1-42) plaques. Fucoxanthin is a carotenoid with potential antioxidant, anti-inflammatory, and neuroprotective actions.

Objective: In the present study, fucoxanthin was employed as a protective strategy in Intracerebroventricular Streptozotocin (ICV-STZ) induced experimental model of cognitive impairment.

Methods: STZ was injected twice ICV (3 mg/kg) on alternate days 1 and 3, and Wistar rats were evaluated for the memory analysis using Morris water maze and elevated plus-maze. Fucoxanthin at low 50 mg/kg, p.o. and high dose 100 mg/kg, p.o. was administered for 14 days. All animals were sacrificed on day 29, and brain hippocampus tissue after isolation was used for biochemical (MDA, nitrite, GSH, SOD and Catalase), neuroinflammatory (TNF-α, IL-1β, and IL-6), neurotransmitters (ACh, GABA Glutamate), Aβ(1-42) and Tau protein measurements.

Results: STZ-infused rats showed significant impairment in learning and memory, increased oxidative stress (MDA, nitrite), reduced antioxidant defense (GSH, SOD and Catalase), promoted cytokine release, and change in neurotransmitters level. However, fucoxanthin improved cognitive functions, restored antioxidant levels, reduced inflammatory markers dose-dependently, and restored neurotransmitters concentration.

Conclusion: The finding of the current study suggests that fucoxanthin could be the promising compound for improving cognitive functions through antioxidant, anti-inflammatory, and neuroprotective mechanisms, and inhibition of acetylcholinesterase (AChE) enzyme activities, Aβ(1-42) accumulation, and tau protein.

Keywords: Fucoxanthin, STZ, cytokines, neurotransmitters, acetylcholinesterase, Alzheimer's disease.

[1]
Hampel H, Mesulam MM, Cuello AC, et al. The cholinergic system in the pathophysiology and treatment of Alzheimer’s disease. Brain 2018; 141(7): 1917-33.
[http://dx.doi.org/10.1093/brain/awy132] [PMID: 29850777]
[2]
Uttara B, Singh AV, Zamboni P, Mahajan RT. Oxidative stress and neurodegenerative diseases: a review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol 2009; 7(1): 65-74.
[http://dx.doi.org/10.2174/157015909787602823] [PMID: 19721819]
[3]
Moneim AE. Oxidant/Antioxidant imbalance and the risk of Alzheimer’s disease. Curr Alzheimer Res 2015; 12(4): 335-49.
[http://dx.doi.org/10.2174/1567205012666150325182702] [PMID: 25817254]
[4]
Singh RP, Sharad S, Kapur S. Free radicals and oxidative stress in neurodegenerative diseases: relevance of dietary antioxidants. J Indian Acad Clin Med 2004; 5(3): 218-25.
[5]
Coyle JT, Puttfarcken P. Oxidative stress, glutamate, and neurodegenerative disorders. Science 1993; 262(5134): 689-95.
[http://dx.doi.org/10.1126/science.7901908] [PMID: 7901908]
[6]
Zhou S, Yu G, Chi L, et al. Neuroprotective effects of edaravone on cognitive deficit, oxidative stress and tau hyperphosphorylation induced by intracerebroventricular streptozotocin in rats. Neurotoxicology 2013; 38: 136-45.
[http://dx.doi.org/10.1016/j.neuro.2013.07.007] [PMID: 23932983]
[7]
Kamat PK, Kalani A, Rai S, Tota SK, Kumar A, Ahmad AS. Streptozotocin intracerebroventricular-induced neurotoxicity and brain insulin resistance: A therapeutic intervention for treatment of sporadic Alzheimer’s disease (sAD)-like pathology. Mol Neurobiol 2016; 53(7): 4548-62.
[http://dx.doi.org/10.1007/s12035-015-9384-y] [PMID: 26298663]
[8]
Lin J, Yu J, Zhao J, et al. Fucoxanthin, a marine carotenoid, attenuates β-amyloid oligomer-induced neurotoxicity possibly via regulating the PI3K/Akt and the ERK pathways in SH-SY5Y cells. Oxid Med Cell Long 2017; 2017: 6792543.
[9]
Zhang H, Tang Y, Zhang Y, et al. Fucoxanthin: A promising medicinal and nutritional ingredient. Evid Based Complement Alternat Med 2015; 2015: 723515.
[http://dx.doi.org/10.1155/2015/723515] [PMID: 26106437]
[10]
Hannan MA, Dash R, Haque MN, et al. Neuroprotective potentials of marine algae and their bioactive metabolites: pharmacological insights and therapeutic advances. Mar Drugs 2020; 18(7): 347.
[http://dx.doi.org/10.3390/md18070347]
[11]
Pangestuti R, Vo TS, Ngo DH, Kim SK. Fucoxanthin ameliorates inflammation and oxidative reponses in microglia. J Agric Food Chem 2013; 61(16): 3876-83.
[http://dx.doi.org/10.1021/jf400015k] [PMID: 23551304]
[12]
Zhao X, Zhang S, An C, et al. Neuroprotective effect of fucoxanthin on β-amyloid-induced cell death. J Chin Pharm Sci 2015; 24(7): 467-74.
[13]
Arora R, Deshmukh R. Embelin attenuates intracerebroventricular streptozotocin-induced behavioral, biochemical, and neurochemical abnormalities in rats. Mol Neurobiol 2017; 54(9): 6670-80.
[http://dx.doi.org/10.1007/s12035-016-0182-y] [PMID: 27744573]
[14]
Paudel P, Seong SH, Jung HA, Choi JS. Characterizing fucoxanthin as a selective dopamine D3/D4 receptor agonist: Relevance to Parkinson’s disease. Chem Biol Interact 2019; 310: 108757.
[http://dx.doi.org/10.1016/j.cbi.2019.108757] [PMID: 31323226]
[15]
Morris R. Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 1984; 11(1): 47-60.
[http://dx.doi.org/10.1016/0165-0270(84)90007-4] [PMID: 6471907]
[16]
Pu D, Kumar Ar. Pharmacological evaluation of triphala churna instreptozotocin (Icv) induced dementia in rats. Int J Pharm Pharm Sci 2018; 10: 97-105.
[http://dx.doi.org/10.22159/ijpps.2018v10i3.22795]
[17]
Shah JS, Goyal RK. Investigation of neuropsychopharmacological effects of a polyherbal formulation on the learning and memory process in rats. J Young Pharma 2011; 3(2): 119-24.
[http://dx.doi.org/10.4103/0975-1483.80296]
[18]
Wang D, Wang C, Liu L, Li S. Protective effects of evodiamine in experimental paradigm of Alzheimer’s disease. Cogn Neurodynamics 2018; 12(3): 303-13.
[http://dx.doi.org/10.1007/s11571-017-9471-z] [PMID: 29765479]
[19]
Largo R, Alvarez-Soria MA, Díez-Ortego I, et al. Glucosamine inhibits IL-1β-induced NFkappaB activation in human osteoarthritic chondrocytes. Osteoarthritis Cartilage 2003; 11(4): 290-8.
[http://dx.doi.org/10.1016/S1063-4584(03)00028-1] [PMID: 12681956]
[20]
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193(1): 265-75.
[http://dx.doi.org/10.1016/S0021-9258(19)52451-6] [PMID: 14907713]
[21]
Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959; 82(1): 70-7.
[http://dx.doi.org/10.1016/0003-9861(59)90090-6] [PMID: 13650640]
[22]
Del Maestro RF, McDonald W, Anderson R. Superoxide dismutase, catalase and glutathione peroxidase in experimental and human brain tumors. Oxygen radicals and their scavenger systems 1983; 2: 28.
[23]
Aebi H. Catalase in vitro. Methods Enzymol 1984; 105: 121-6.
[http://dx.doi.org/10.1016/S0076-6879(84)05016-3] [PMID: 6727660]
[24]
Ellman GL, Courtney KD. Andres VJr, and feather-stone RM. Biochem Pharmacol 1961; 7: 88-95.
[http://dx.doi.org/10.1016/0006-2952(61)90145-9] [PMID: 13726518]
[25]
Donzanti BA, Yamamoto BK. An improved and rapid HPLC-EC method for the isocratic separation of amino acid neurotransmitters from brain tissue and microdialysis perfusates. Life Sci 1988; 43(11): 913-22.
[http://dx.doi.org/10.1016/0024-3205(88)90267-6] [PMID: 2901021]
[26]
Wang L, Maher TJ, Wurtman RJ. Oral L-glutamine increases GABA levels in striatal tissue and extracellular fluid. FASEB J 2007; 21(4): 1227-32.
[http://dx.doi.org/10.1096/fj.06-7495com] [PMID: 17218538]
[27]
Galasko D, Montine TJ. Biomarkers of oxidative damage and inflammation in Alzheimer’s disease. Biomarkers Med 2010; 4(1): 27-36.
[http://dx.doi.org/10.2217/bmm.09.89] [PMID: 20383271]
[28]
Poljsak B, Šuput D, Milisav I. Achieving the balance between ROS and antioxidants: when to use the synthetic antioxidants. Oxid Med Cell Long 2013; 2013: 956792.
[http://dx.doi.org/10.1155/2013/956792]
[29]
Huang XB, Chen YJ, Chen WQ, Wang NQ, Wu XL, Liu Y. Neuroprotective effects of tenuigenin on neurobehavior, oxidative stress, and tau hyperphosphorylation induced by intracerebroventricular streptozotocin in rats. Brain Circ 2018; 4(1): 24-32.
[http://dx.doi.org/10.4103/bc.BC_2_17] [PMID: 30276333]
[30]
Tota S, Kamat PK, Shukla R, Nath C. Improvement of brain energy metabolism and cholinergic functions contributes to the beneficial effects of silibinin against streptozotocin induced memory impairment. Behav Brain Res 2011; 221(1): 207-15.
[http://dx.doi.org/10.1016/j.bbr.2011.02.041] [PMID: 21382422]
[31]
Anand KS, Dhikav V. Hippocampus in health and disease: An overview. Ann Indian Acad Neurol 2012; 15(4): 239-46.
[http://dx.doi.org/10.4103/0972-2327.104323] [PMID: 23349586]
[32]
Barai P, Raval N, Acharya S, Acharya N. Bergenia ciliata ameliorates streptozotocin-induced spatial memory deficits through dual cholinesterase inhibition and attenuation of oxidative stress in rats. Biomed Pharmacother 2018; 102: 966-80.
[http://dx.doi.org/10.1016/j.biopha.2018.03.115] [PMID: 29710552]
[33]
Lin J, Huang L, Yu J, et al. Fucoxanthin, a marine carotenoid, reverses scopolamine-induced cognitive impairments in mice and inhibits acetylcholinesterase in vitro. Mar Drugs 2016; 14(4): 67.
[http://dx.doi.org/10.3390/md14040067] [PMID: 27023569]
[34]
Xiang S, Liu F, Lin J, et al. Fucoxanthin inhibits β-amyloid assembly and attenuates β-amyloid oligomer-induced cognitive impairments. J Agric Food Chem 2017; 65(20): 4092-102.
[http://dx.doi.org/10.1021/acs.jafc.7b00805] [PMID: 28478680]
[35]
Zamani Z, Reisi P, Alaei H, Pilehvarian AA. Effect of Royal Jelly on spatial learning and memory in rat model of streptozotocin-induced sporadic Alzheimer’s disease. Adv Biomed Res 2012; 1: 26.
[http://dx.doi.org/10.4103/2277-9175.98150] [PMID: 23210085]
[36]
Singh S, Jamwal S, Kumar P. Piperine enhances the protective effect of curcumin against 3-NP induced neurotoxicity: possible neurotransmitters modulation mechanism. Neurochem Res 2015; 40(8): 1758-66.
[http://dx.doi.org/10.1007/s11064-015-1658-2] [PMID: 26160706]
[37]
Gao HM, Zhou H, Hong JS. Oxidative stress, neuroinflammation, and neurodegeneration InNeuroinflammation and neurodegeneration. New York, NY: Springer 2014; pp. 81-104.
[38]
Kurutas EB. The importance of antioxidants which play the role in cellular response against oxidative/nitrosative stress: current state. Nutr J 2016; 15(1): 71.
[http://dx.doi.org/10.1186/s12937-016-0186-5] [PMID: 27456681]
[39]
De Felice FG, Velasco PT, Lambert MP, et al. Abeta oligomers induce neuronal oxidative stress through an N-methyl-D-aspartate receptor-dependent mechanism that is blocked by the Alzheimer drug memantine. J Biol Chem 2007; 282(15): 11590-601.
[http://dx.doi.org/10.1074/jbc.M607483200] [PMID: 17308309]
[40]
Wang WY, Tan MS, Yu JT, Tan L. Role of pro-inflammatory cytokines released from microglia in Alzheimer’s disease. Ann Transl Med 2015; 3(10): 136.
[PMID: 26207229]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy