Neuroprotective and Anti-ageing Effects of Curcumin in Aged Rat Brain Regions
This study investigated the influence of chronically administered curcumin on normal ageing-related parameters: lipid peroxidation, lipofuscin concentration and intraneuronal lipofuscin accumulation, activities of the enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and Na+, K+, -adenosine triphosphatase (Na+, K+, -ATPase) in different brain regions (cerebral cortex, hippocampus, cerebellum and medulla) of 6- and 24-month-old rats. In normal ageing, lipid peroxidation and lipofuscin concentration were found to increase with ageing, the activities of SOD, GPx and Na+, K+, -ATPase, however, decreased with ageing. Chronic curcumin treatment of both 6 and 24 months old rats resulted in significant decreases in lipid peroxide and the lipofuscin contents in brain regions, the activities of SOD, GPx and Na+, K+, -ATPase however, showed significant increase in various brain regions. The present study, thus, demonstrated the antioxidative, antilipofusinogenesic and anti-ageing effects of curcumin in the brain.
Keywordsanti-ageing effects antioxidant enzymes curcumin lipofuscin Na + K+-ATPase
Barcley, LR, Vinqvist, MR, Mukai, K, Goto, H, Hashimoto, Y, Tokunaga, A, Uno, H 2000On the antioxidant mechanism of curcumin: classical methods are needed to determine antioxidant mechanism and activityOrg Lett728412843CrossRefGoogle Scholar Calabrese, V, Butterfield, DA, Stella, AM 2003Nutritional antioxidants and the heme oxygenase pathway of stress tolerance: novel targets for neuroprotection in Alzheimer’s diseaseItal J Biochem52177181PubMedGoogle Scholar Cardozo-pelaez, F, Brooks, PJ, Stedeford, T, Song, S, Sanchez-Ramos, J 2000DNA damage, repair and antioxidant systems in brain regions: a correlative studyFree Radic Biol Med28779785PubMedCrossRefGoogle Scholar Crambert, G, Fuzesi, M, Garty, H, Karlish, S, Greeing, K 2002Phospholemman (FXYDI) associate with Na+, K+-ATPase and regulate its transport propertiesProc Natl Acad Sci USA991147611481PubMedCrossRefGoogle Scholar Deodhar, SD, Sethi, R, Srimal, RC 1980Preliminary study on antirheumatic activity of curcumin (diferuloylmethane)Indian J Med Res71601608Google Scholar Donatus, IA Sardjoko and Vermeulen NP1990Cytotoxic and cytoprotective activities of curcumin. Effect of paracetamol-induced cytotoxicity, lipid per oxidation and glutathione depletion in rat hepatocytesBiochem Pharmacol3918691875PubMedCrossRefGoogle Scholar Esterbaur, H, Schaur, RJ, Zollner, H 1991Chemistry and biochemistry of hydroxynonenal, malondialdehyde and related aldehydesFree Radic Biol Med1181128CrossRefGoogle Scholar Feschenko, MS, Donnet, C, Wetzel, RK, Asinovski, NK, Jones, LR, Sweadner, KJ 2003Phospholemman, a single-span membrane protein, is an accessory protein of Na+, K+ -ATPase in cerebellum and choroid plexusJ Neurosci2321612169PubMedGoogle Scholar Fletcher, BL, Dillard, CJ, Tapple, AL 1973Measurement of fluorescent per oxidation products in biological systems and tissuesAnal Biochem5219PubMedCrossRefGoogle Scholar Flohe, L, Gunzler, WA 1984Assays of glutathione peroxidasePacker, P eds. Methods of EnzymologyAcademic PressNew York114121Google Scholar Frautschy, SA, Hu, W, Kim, P, Miller, SA, Chu, T, Herris-White, ME, Cole, GM 2001Phenolic anti-inflammatory antioxidant reversal of a beta-induced cognitive deficits and neuropathologyNeurobiol Aging229931005PubMedCrossRefGoogle Scholar Fuller, W, Eatson, P, Bell, JR, Shattock, MJ 2003Ischemia-induced Phosphorylation of phospholemman directly activates rat cardiac Na+, K+-ATPaseFASEB1010961116Google Scholar Gopal, PV, Sriram, AV, Sharma, D, Singh, R 2000Glutathione-S-transferase in the ageing rat brain cerebrum and the effect of chlorpromazineGerontology46711PubMedCrossRefGoogle Scholar Inano, H, Onoda, M, Inafuku, N, Kubota, M, Kamada, Y, Osawa, T, Kobayashi, H, Wakabayashi, K 2000Potent preventive action of curcumin on radiation-induced initiation of mammary tumorigenesis in ratsCarcinogenesis2118351841PubMedCrossRefGoogle Scholar Jovanovic, SV, Boone, CW, Steenken, S, Trinoga, M, Kaskey, RB 2001How curcumin works preferentially with water soluble antioxidantsJ Am Chem Soc12330643068PubMedCrossRefGoogle Scholar Kaul, S, Krishnakanth, TP 1994Effect of retinal deficiency and curcumin or turmeric feeding on brain Na+, K+, -ATPase adenosine triphosphate activityMol Cell Biochem137101107PubMedCrossRefGoogle Scholar Kaur, J, Sharma, D, Singh, R 1998Regional effects of ageing Na+, K+ -ATPase activity in rat brain and correlation with multiple unit action potentials and lipid peroxidationIndian J Biochem Biophys35364371PubMedGoogle Scholar Marklund, S, Marklund, G 1974Involvement of the super oxide Anion radical in the autooxidation of pyrogallol and convenient assay for Super oxide DismutaseEur J Biochem47469474PubMedCrossRefGoogle Scholar Masuda, T, Maekawa, T, Hidaka, K, Bando, H, Takeda, Y, Yamaguchi, H 2001Chemical studies on antioxidant mechanisms of curcumin: analysis of oxidative coupling products from curcumin and linoleateJ Agric Food Chem4925392547PubMedCrossRefGoogle Scholar Mattson, MP 1998Modification of ion homeostasis by lipid peroxidation: role of neuronal degeneration and adaptive plasticityTrends Neurosci215357PubMedCrossRefGoogle Scholar Mukhopadhyay, A, Basu, N, Ghatak, N, Gujral, PK 1982Anti-inflammatory and irritant activities of curcumin analogues in ratsAgents Actions12508515PubMedCrossRefGoogle Scholar Okhawa, H, Ohishi, N, Yagi, K 1979Assay for lipid peroxide in animal tissue by thiobarbituric acid reactionAna Biochem95351358CrossRefGoogle Scholar Osawa, T, Kato, Y 2005Protective role of antioxidative food factors in oxidative stress caused by hyperglycemiaAnn NY Acad Sci1043440451PubMedCrossRefGoogle Scholar Park, EJ, Jeon, CH, Ko, G, Kim, J, Sohn, DH 2000Protective effect of curcumin in rat liver injury induced by carbon tetrachlorideJ Pharm Pharmacol52437440PubMedCrossRefGoogle Scholar Patil, TN, Srinevasan, M 1971Hypocholesteremic effect of curcumin in induced-hypercholesteremic ratsIndian J Exp Biol9167169PubMedGoogle Scholar Piper, JT, Singhal, SS, Salameh, MS, Torman, RT, Awasthi, YC, Awasthi, S 1998Mechanism of anticarcinogenic properties of curcumin: the effect of curcumin on glutathione linked detoxification enzyme in rat liverInt J Biochem Cell Biol30445456PubMedCrossRefGoogle Scholar Quiles, JL, Aguilera, C, Mesa, MD, Ramirez-Tortosa, MC, Gil, A 1998An ethanolic-aqueous extract of curcuma longa decrease the susceptibility of liver microsomes and mitochondria to lipid per oxidation in atherosclerotic RabbitBiofactor85157Google Scholar Rajakumar, DV, Rao, MN 1994Antioxidant properties of dehydrozingerone and curcumin in rat brain homogenatesMol Cell Biochem1407379PubMedCrossRefGoogle Scholar Rajkrishnan, V, Vishwanathan, P, Rajasekharan, KN, Menon, VP 1999Neuroprotective role of curcumin from curcuma longa on ethanol-induced brain damagePhytother Res13571574CrossRefGoogle Scholar Reddy, A Ch, Lokesh, BR 1994Studies on the inhibitory effects of curcumin and eugenol on the formation of reactive oxygen species and oxidation of ferrous ionsMol Cell Biochem13718PubMedCrossRefGoogle Scholar Reddy, A Ch, Lokesh, BR 1996Effect of turmeric (Curcuma longa) on iron-induced lipid per oxidation in the rat liverFood Chem Toxicol32279283CrossRefGoogle Scholar Riga, S, Riga, D 1974Effects of centrophenoxine on the lipofuscin pigments in nervous system of old ratsBrain Res72265275PubMedCrossRefGoogle Scholar Ruby, AJ, Kuttan, G, Babu, KD, Rajasekharan, KN, Kuttan, R 1995antitumor and antioxidant activity of natural curcuminoidsCancer Lett947983PubMedCrossRefGoogle Scholar Sharma, D, Maurya, AK, Singh, R 1993Age-related decline in multiple unit action potentials of CA3 regions of rat hippocampus: correlation with lipid peroxidation and lipofuscin concentration and the effect of centrophenoxineNeurobiol Aging14319330PubMedCrossRefGoogle Scholar Srimal, RC, Dhawan, BN 1973Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agentJ Pharm Pharmacol25447452PubMedGoogle Scholar Sreejayan, N, Rao, MN 1994Curcumoids as potent inhibitors of lipid per oxidationJ Pharm Pharmacol4610131016PubMedGoogle Scholar Srinivasan, M 1972Effect of curcumin on blood sugar as seen in diabetic subjectIndian J Med Sci26269270PubMedGoogle Scholar Sun, YM, Zhang, HY, Chen, DZ, Liu, CB 2002Theoretical elucidation on the antioxidant mechanism of curcumin: a DFT studyOrg Lett4290929011PubMedCrossRefGoogle Scholar Surh, YJ 1999Molecular mechanisms of chemopreventive effects of selected dietary and medicinal phenolic substancesMutat Res428305327PubMedGoogle Scholar Tanaka, Y, Ando, S 1990Synaptic ageing as revealed by changes in membrane potential and decreased activity of Na+, K+-ATPaseBrain Res43425434Google Scholar Thiyagarajan, M, Sharma, SS 2004Neuroprotective effect of curcumin in middle cerebral artery occlusion induced focal cerebral ischemia in ratsLife Sci74969985PubMedCrossRefGoogle Scholar Vajragupta, O, Boonchoong, P, Watanabe, H, Tohda, M, Kummasud, N, Sumanont, Y 2003Manganese complexes of curcumin and its derivatives: evaluation for the radical scavenging ability and neuroprotective activityFree Radic Biol Med3516321644PubMedCrossRefGoogle Scholar Viani, P, Ceravto, G, Fiorilli, A, Cestaro, B 1991Age-related differences in synaptosomal peroxidative damage and membrane propertiesJ Neurochem56253258PubMedGoogle Scholar Watanabe, S, Fukui, T 2000Suppressive effect of curcumin on trichloroethane-induced oxidative stressJ Nutr Sci Vitaminol (Tokyo)46230234Google Scholar