AAD  Vol.4 No.3 , September 2015
Chronic Administration of Curcuma longa Extract Improves Spatial Memory-Related Learning Ability in Aged Rats by Inhibiting Brain Cortico-Hippocampal Oxidative Stress and TNFα
Abstract: We studied on the effect of Curcuma longa extract on spatial learning-related memory ability of old rats in eight-arm radial maze task. Rats were randomly divided into two groups: one group was orally administered 100 mg/KgBW/day C. longa extract (CLE) dissolved in deionized water and the other group was administered the vehicle alone for 10 weeks. The rats were tested with the partially baited eight-arm radial maze to evaluate two types of spatial memory-related learning ability displayed by reference memory errors (RMEs) and working memory errors (WMEs). Chronic administration of CLE significantly decreased the number of RMEs and WMEs, concurrently with the decreases in the cortico-hippocampal levels of lipid peroxides (LPO) and tumor necrosis factor alpha (TNF-α). In a parallel set of experiments, CLE-pretreated rats of the same age group were subjected to hypoxia-reperfusion injury by carotid artery occlusion to induce oxidative stress in the brains in order to examine whether such an in vivo hypoxia-induced oxidative stress could be ameliorated by the extract. Again, the levels of LPO were significantly decreased in the cortico-hippocampal tissues of the CLE-fed hypoxic rats. The histology of the brains also revealed that the CLE-pretreated rats had retained improved cellular integrity. Finally, our results provide the evidence that oral administration of C. longa extract increases the defense against oxidative stress and proinflammatory TNF-α, concurrently with the improvement of memory-related brain cognitive ability of the aged rats.
Cite this paper: Akter, F. , Haque, M. , Islam, J. , Rahaman, A. , Bhowmick, S. and Hossain, S. (2015) Chronic Administration of Curcuma longa Extract Improves Spatial Memory-Related Learning Ability in Aged Rats by Inhibiting Brain Cortico-Hippocampal Oxidative Stress and TNFα. Advances in Alzheimer's Disease, 4, 78-89. doi: 10.4236/aad.2015.43008.

[1]   Goel, A., Kunnumakkara, A.B. and Aggarwal, B.B. (2007) Curcumin as Curecumin: from Kitchen to Clinic. Biochemical Pharmacology, 75, 787-809.

[2]   Aggarwal, B.B. and Harikumar, K.B. (2009) Potential Therapeutic Effects of Curcumin, the Anti-Inflammatory Agent against Neurodegenerative, Cardiovascular, Pulmonary, Metabolic, Autoimmune and Neoplastic Diseases. International Journal of Biochemistry & Cell Biology, 41, 40-59.

[3]   Hatcher, H., Planalp, R. Cho, J., Torti, F.M. and Torti, S.V. (2008) Curcumin: From Ancient Medicine to Current Clinical Trials. Cellular and Molecular Life Sciences, 65, 1631-1652.

[4]   Hiserodt, R., Hartman, T.G., Ho, C.T. and Rosen, R.T. (1996) Characterization of Powdered Turmeric by Liquid Chromatography-Mass Spectrometry and Gas Chromatography-Mass Spectrometry. Journal of Chromatography, 740, 51-63.

[5]   Bala, K., Tripathy, B.C. and Sharma, D. (2006) Neuroprotective and Antiageing Effects of Curcumin in Aged Rat Brain Regions. Biogerontology, 7, 81-89.

[6]   Ramirez-Tortosa, M.C., Mesa, M.D., Aguilera, M.C., Quiles, J.L., Baro, L., Ramirez-Tortosa, C.L., Martinez-Victoria, E. and Gil, A. (1999) Oral Administration of Turmeric Extract Inhibits LDL Oxidation and Has Hypocholesterolemic Effects in Rabbits with Experimental Atherosclerosis. Atherosclerosis, 147, 371-378.

[7]   Ono, K., Hasegawa, K., Naiki, H. and Yamada, M. (2004) Curcumin Has Potent Anti-Myloidogenic Effects for Alzheimer’s Beta-Amyloid Fibrils in Vitro. Journal of Neuroscience Research, 75, 742-750.

[8]   Yang, F., Lim, G.P., Begum, A.N., Ubeda, O.J., Simmons, M.R., Ambegaokar, S.S., Chen, P.P., Kayed, R., Glabe, C.G., Frautschy, S.A. and Cole, G.M. (2005) Curcumin Inhibits Formation of Amyloid Beta Oligomers and Fibrils, Binds Plaques and Reduces Amyloid in Vivo. Journal of Biological Chemistry, 280, 5892-5901.

[9]   Garcia-Alloza, M., Borrelli, L.A., Rozkalne, A., Hyman, B.T. and Bacskai, B.J. (2007) Curcumin Labels Amyloid Pathology in Vivo, Disrupts Existing Plaques and Partially Restores Distorted Neurites in an Alzheimer Mouse Model. Journal of Neurochemistry, 102, 1095-1104.

[10]   Frautschy, S.A., Hu, W., Kim, P., Miller, S.A., Chu, T., Harris-White, M.E. and Cole, G.M. (2001) Phenolic Anti-Inflammatory Antioxidant Reversal of Abeta-Induced Cognitive Deficits and Neuropathology. Neurobiology of Aging, 22, 993-1005.

[11]   Kim, H.Y., Park, E.J., Joe, E.H. and Jou, I. (2003) Curcumin Suppresses Janus Kinase-STAT Inflammatory Signaling through Activation of Src Homology 2 Domain-Containing Tyrosine Phosphatase 2 in Brain Microglia. The Journal of Immunology, 171, 6072-6079.

[12]   Jung, K.K., Lee, H.S., Cho, J.Y., Shin, W.C., Rhee, M.H., Kim, T.G., Kang, J.H., Kim, S.H., Hong, S. and Kang, S.Y. (2006) Inhibitory Effect of Curcumin on Nitric Oxide Production from Lipopolysaccharide-Activated Primary Microglia. Life Sciences, 79, 2022-2031.

[13]   Zhao, B.L.X., Li, J., He, R.G., Cheng, S.J. and Xin, W.J. (1989) Scavenging Effect of Extracts of Green Tea and Natural Antioxidants on Active Oxygen Radicals. Cell Biophysics, 14, 175-185.

[14]   Pyrzanowska, J., Piechal, A., Klin, K.B., Lehner, M., Skórzewska, A., Turzyńska, D., Sobolewska, A., Plaznik, A. and Tyszkiewicz, E.W. (2010) The Influence of the Long-Term Administration of Curcuma longa Extract on Learning and Spatial Memory as Well as the Concentration of Brain Neurotransmitters and Level of Plasma Corticosterone in Aged Rats. Pharmacology Biochemistry and Behavior, 95, 351-358.

[15]   Hodges, H. (1996) Maze Procedures: The Radial-Arm and Water Maze Compared. Cognitive Brain Research, 3, 167- 181.

[16]   Gamoh, S., Hashimoto, M., Sugioka, K., Hossain, S.M., Hata, N., Misawa, Y. and Masumura, S. (1999) Chronic Administration of Docosahexaenoic Acid Improves Reference Memory Related Learning Ability in Young Rats. Neuroscience, 93, 237-241.

[17]   Gerrard, J.L., Burke, S.N., McNaughton, B.L. and Barnes, C.A. (2008) Sequence Reactivation in the Hippocampus Is Impaired in Aged Rats. The Journal of Neuroscience, 28, 7883-7890.

[18]   Ohkawa, H., Ohnishi, N. and Yagi, K. (1979) Assay for Lipid Peroxidation in Animal Tissue by Thiobarbituric Acid Reaction. Analytical Biochemistry, 95, 351-358.

[19]   Haque, M., Islam, J., Rahaman, A., Selina, F.A., Rahman, M.A., Hasan, M. and Hossain, S. (2014) Raphanus sativus Ameliorates Atherogeneic Lipid Profiles in Hypercholesterolemic Rats and Hypercholesterolemia-Associated Peroxidative Liver Damage. Journal of Advanced Chemistry, 7, 1385-1394.

[20]   Lowry, O.H., Rosebrough, N.J., Farr, A.L. and Randall, R.J. (1951) Protein Measurement with the Folin Reagent. The Journal of Biological Chemistry, 193, 265-275.

[21]   Islam, J., Haque, M., Rahaman, A. and Hossain, S. (2014) Syzygium cumini (L.) Seed Extract Protects Embryofoetal Brains against Intrauterine Oxidative Toxicity in Rats during Hypoxia-Reperfusion Injury. International Journal of Pharmaceutical Sciences and Research, 3, 170-177.

[22]   Iwasaki, Y., Ito, S., Suzuki, M., Nagahori, T., Yamamoto, T. and Konno, H. (1989) Forebrain Ischemia Induced by Temporary Bilateral Common Carotid Occlusion in Normotensive Rats. Journal of the Neurological Sciences, 90, 155- 165.

[23]   Raghavendra, M., Trigunayat, A., Singh, R.K., Mitra, S., Goel, R.K. and Acharya, S.B. (2007) Effect of Ethanolic Extract of Root of Pongamia pinnata (L.) Pierre on Oxidative Stress, Behavioral and Histopathological Alterations Induced by Cerebral Ischemia—Reperfusion and Long-Term Hypoperfusion in Rats. Indian Journal of Experimental Biology, 45, 868-876.

[24]   Rahaman, A., Hossain, S., Rahman, M., Hossain, I., Nahar, T., Uddin, B. and Khalil, I. (2013) Syzygium cumini (L.) Seed Extract Improves Memory Related Learning Ability of Old Rats in Eight Arm Radial Maze. Journal of Pharmacognosy and Phytochemistry, 1, 85-94.

[25]   Amin, I., Norazaidah, Y. and Hainida, K.I.E. (2006) Antioxidant Activity and Phenolic Content of Raw and Blanched Amaranthus Species. Food Chemistry, 94, 47-52.

[26]   Kumar, S., Kumar, D., Manjusha, K., Saroha, S.N. and Vashishta, B. (2008) Antioxidant Free Radical Scavenging Potential of Citrullus colocynthis (L.) Schrad. Methanolic Fruit Extract. Acta Pharmaceutica, 58, 215-220.

[27]   Hossain, S., Rahaman, A., Nahar, T., Basunia, M.A., Rahman, F., Uddin, B., Shahriar, M. and Mahmud, I. (2011) Syzygium cumini (L.) Skeels Seed Extract Ameliorates in Vitro and in Vivo Oxidative Potentials of the Brain Cerebral Cortex of Alcohol-Treated Rats. Oriental Pharmacy and Experimental Medicine, 12, 59-66.

[28]   Barnes, C.A., Nadel, L. and Honig, W.K. (1980) Spatial Memory Deficit in Senescent Rats. Canadian Journal of Psychology, 34, 29-39.

[29]   Gallagher, M. and Burwell, R.D. (1989) Relationship of Age-Related Decline across Several Behavioral Domains. Neurobiology of Aging, 10, 691-708.

[30]   Oler, J.A. and Markus, E.J. (1998) Age-Related Deficits on the Radial Maze and in Fear Conditioning: Hippocampal Processing and Consolidation. Hippocampus, 8, 402-415.<402::AID-HIPO8>3.0.CO;2-I

[31]   Goto, S., Naito, H., Kaneko, T., Chung, H.Y. and Radak, Z. (2007) Hormetic Effects of Exercise in Aging: Correlation with Oxidative Stress. Applied Physiology, Nutrition, and Metabolism, 32, 948-953.

[32]   Jerrard, L.E. and Okaichi, H. (1984) On the Role of Hippocampal Connections in the Performance of Place and Clue Tasks: Comparisons with Damage to Hippocampus. Behavioral Neuroscience, 98, 946-954.

[33]   Eybl, V., Kotyzova, D. and Koutensky, J. (2006) Comparative Study of Natural Antioxidants—Curcumin, Resveratrol and Melatonin—In Cadmium-Induced Oxidative Damage in Mice. Toxicology, 225, 150-156.

[34]   Motterlini, R., Foresti, R., Bassi, R. and Green, C.J. (2000) Curcumin, an Antioxidant and Anti-Inflammatory Agent, Induces Heme Oxygenase-1 and Protects Endothelial Cells against Oxidative Stress. Free Radical Biology & Medicine, 28, 1303-1312.

[35]   Rajakrishnan, V., Viswanathan, P., Rajasekharan, K.N. and Menon, V.P. (1999) Neuroprotective Role of Curcumin from Curcuma longa on Ethanol-Induced Brain Damage. Phytotherapy Research, 13, 571-574.<571::AID-PTR494>3.0.CO;2-7

[36]   Fillit, H., Ding, W.H., Buee, L., Kalman, J., Altstiel, L., Lawlor, B. and Wolf-Klein, G. (19991) Elevated Circulating Tumor Necrosis Factor Levels in Alzheimer’s Disease. Neuroscience Letters, 129, 318-320.

[37]   Boka, G., Anglade, P., Wallach, D., Javoy-Agid, F., Agid, Y. and Hirsch, E.C. (1994) Immunocytochemical Analysis of Tumor Necrosis Factor and Its Receptors in Parkinson’s Disease. Neuroscience Letters, 172, 151-154.

[38]   Lourenco, M.V., Clarke, J.R., Frozza, R.L., Bomfim, T.R., Forny-Germano, L., Batista, A.F., et al. (2013) TNF-α Mediates PKR-Dependent Memory Impairment and Brain IRS-1 Inhibition Induced by Alzheimer’s β-Amyloid Oligomers in Mice and Monkeys. Cell Metabolism, 18, 831-843.

[39]   Liu, B., Zupan, B., Laird, E., Klein, S., Gleason, G., Bozinoski, M., Toth, J.G. and Toth, M. (2013) Maternal Hematopoietic TNF, via Milk Chemokines, Programs Hippocampal Development and Memory. Nature Neuroscience, 17, 97- 105.

[40]   Suematsu, N., Tsutsui, H., Wen, J., Kang, D., Ikeuchi, M., Ide, T., Hayashidani, S., Shiomi, T., Kubota, T., Hamasaki, N. and Takeshita, A. (2003) Oxidative Stress Mediates Tumor Necrosis Factor-Alpha-Induced Mitochondrial DNA Damage and Dysfunction in Cardiac Myocytes. Circulation, 107, 1418-1423.

[41]   Schaller, B. and Graf, R. (2004) Cerebral Ischemia and Reperfusion: The Pathophysiologic Concept as a Basis for Clinical Therapy. Journal of Cerebral Blood Flow & Metabolism, 24, 351-371.

[42]   Fischer, W., Gage, F.H. and Björklund, A. (1989) Degenerative Changes in Forebrain Cholinergic Nuclei Correlate with Cognitive Impairments in Aged Rats. European Journal of Neuroscience, 1, 34-45.

[43]   Davis, H.P. and Squire, L.R. (1984) Protein Synthesis and Memory. Psychological Bulletin, 96, 518-559.

[44]   Burke, S.N. and Barnes, C.A. (2006) Neural Plasticity in the Ageing Brain. Neuroscience, 7, 30-40.