Influence of long-term administration of Curcuma longa extract on explorative activity in aged rats
More details
Hide details
Department of Experimental and Clinical Pharmacology, Medical University, Warsaw, Poland
Department of Biochemistry, Medical University, Warsaw, Poland
Justyna Pyrzanowska   

PhD, Department of Experimental and Clinical Pharmacology, Medical University, Krakowskie Przedmieście 26/28, 00-927 Warsaw, Poland, tel./fax. +48 22 826 21 16.
J Pre Clin Clin Res. 2010;4(2):134–140
The effects of long-term administration of a standardised extract of Curcuma longa on the explorative activity in aged 24-month-old male Wistar rats were estimated in a hole-board test. The animals received the extract orally for two months in rodent chow at doses of 10 and 50 mg/kg/day. The correlations between concentration of some neurotransmitters and amino acids in selected brain regions, as well as the level of corticosterone in plasma (described previously), and the parameters of exploration were calculated. The antioxidant processes (GSH, GST, CAT and MDA levels) in heart and skeletal muscles were also investigated. The results suggested that the explorative activity of plant extract-treated rats was enhanced; however, no correlations between brain neurotransmitter concentration or plasma corticosterone level and the parameters of explorative activity were observed. In biochemical investigation, chronic C. longa extract administration influenced antioxidant processes (CAT, GST and MDA levels) in skeletal muscles of aged rats, but not in the heart muscle.
Pyrzanowska J, Piechal A, Blecharz-Klin K, Lehner M, Skorzewska A, Turzyńska D, Sobolewska A, Plaznik A, Widy-Tyszkiewicz E: 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. Pharmacol Biochem Beh 2010, 95, 351-358.
Goel A, Kunnumakkara AB, Aggarwal BB: Curcumin as “Curecumin”: from kitchen to clinic. Biochem Pharmacol 2008, 75, 787-809.
Aggarwal BB, Harikumar KB: Potential therapeutic effects of curcumin, the anti-inflammatory agent against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. Int J Biochem Cell Biol 2009, 41, 40-59.
Hiserodt R, Hartman TG, Ho CT, Rosen RT: Characterization of powdered turmeric by liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. J Chromatogr A 1996, 740, 51-63.
Yamamoto H, Hanada K, Kawasaki K, Nishijima M: Inhibitory effect of curcumin on mammalian phospholipase D activity. FEBS Letters 1997, 417, 196-198.
Khopde SM, Priyadarsini KI, Venkatesan P, Rao MN (1999) Free radical scavenging ability and antioxidant efficiency of curcumin and its substituted analogue. Biophys Chem 80: 85-91.
Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM: The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 2001, 21, 8370-8377.
Quiles JL, Mesa MD, Ramirez-Tortosa CL, Aguilera CM, Battino M, Gil A, Ramirez-Tortosa MC: Curcuma longa extract supplementation reduces oxidative stress and attenuates aortic fatty streak development in rabbits. Arterioscler Thromb Vasc Biol 2002, 22, 1225-1231.
Hong J, Bose M, Ju J, Ryu JH, Chen XC, Sang S, Lee MJ, Yang CS: Modulation of arachidonic acid metabolism by curcumin and related b-diketone derivatives: effects on cytosolic phospholipase A2, cyclooxygenases and 5-lipooxygenase. Carcinogenesis 2004, 25, 1671-1679.
Bala K, Tripathy BC, Sharma D: Neuroprotective and anti-ageing effects of curcumin in aged rat brain regions. Biogerontology 2006, 7, 81-89.
Jacob A, Wu R, Zhou M, Wang P: Mechanism of the anti-inflammatory effect of curcumin: PPAR-γ activation. PPAR Res, 2007 doi: 10.1155/2007/89369.
Zafir A, Banu N: Antioxidant potential of fluoksetine in comparison to Curcuma longa in restaint-stressed rats. Eur J Pharmacol 2007, 572, 23-31.
Frautschy SA, Hu W, Kim P, Miller SA, Chu T, Harris-White ME, Cole GM: Phenolic anti-inflammatory antioxidant reversal of Abeta-induced cognitive deficits and neuropathology. Neurobiol Aging 2001, 22, 993- 1005.
Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP, Kayed R, Glabe CG, Frautschy SA, Cole GM: Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques and reduces amyloid in vivo. J Biol Chem 2005, 280, 5892-5901.
Garcia-Alloza M, Borrelli LA, Rozkalne A, Hyman BT, Bacskai BJ: Curcumin labels amyloid pathology in vivo, disrupts existing plaques and partially restores distorted neurites in an Alzheimer mouse model. J Neurochem 2007, 102, 1095-1104.
Xu Y, Ku B, Cui L, Li X, Barish PA, Foster TC, Ogle WO: Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats. Brain Res 2007, 1162, 9-18.
Sandur SK, Ichikawa H, Pandey MK, Kunnumakkara AB, Sung B, Sethi G, Aggarwal BB: Role of pro-oxidants and antioxidants in the anti-inflammatory and apoptotic effects ofcurcumin (diferuloylmethane). Free Radic Biol Med 2007, 43, 568-580.
Ramirez-Tortosa MC, Mesa MD, Aguilera MC, Quiles JL, Baro L, Ramirez-Tortosa CL, Martinez-Victoria E, Gil A: Oral administration of turmeric extract inhibits LDL oxidation and has hypocholesterolemic effects in rabbits with experimental atherosclerosis. Atherosclerosis 1999, 147, 371-378.
Daniel S, Limson JL, Dairam A, Watkins GM, Daya S: Through metal binding, curcumin protects against lead- and cadmium- induced lipid peroxidation in rat brain homogenates and against lead-induced tissue damage in rat brain. J Inorg Biochem 2004, 98, 266-275.
Maheshwari RK, Singh AK, Gaddipati J, Srimal RC: Multiple biological activities of curcumin: A short review. Life Sci 2006, 78, 2081-2087.
Matteucci A, Frank C, Domenici MR, Balduzzi M, Paradisi S, Carnovale- Scalzo G, Scorcia G, Malchiodi-Albedi F: Curcumin treatment protects rat retinal neurons against excitotoxicity: effect on N-methyl-Daspartate- induced intracellular Ca2+ increase. Exp Brain Res 2005, 167, 641-648.
Suh HW, Kang S, Kwon KS: Curcumin attenuates glutamate-induced HT22 cell death by supressing MAP kinase signaling. Moll Cell Biochem 2007, 298, 187-194.
Ghoneim AI, Abdel-Naim AB, Khalifa AE, El-Denshary ES: Protective effects of curcumin against ischemia/reperfusion insult in rat forebrain. Pharmacol Res 2002, 46, 273-279.
Zhao J, Zhao Y, Zheng W, Lu Y, Feng G, Yu S: Neuroprotective effect of curcumin on transient focal cerebral ischemia in rats. Brain Res 2008, 1229, 224-232.
Kuhad A, Chopra K: Curcumin attenuates diabetic encephalopathy in rats: behavioral and biochemical evidences. Eur J Pharmacol 2007, 576, 34-42.
Conboy L, Foley AG, O´Boyle NM, Lawlor M, Gallagher HC, Murphy KJ, Regan CM: Curcumin-induced degradation of PKCδ is associated with enhanced dentate NCAM PSA expression and spatial learning in adult and aged Wistar rats. Biochem Pharmacol 2009, 77, 1254- 1265.
Xia X, Cheng G, Pan Y, Xia ZH, Kong LD: Behavioral, neurochemical and neuroendocrine effects of ethanolic extract from Curcuma longa L. in the mouse forced swimming test. J Ethnopharmacol 2007, 110, 356-363.
Bishnoi M, Chopra K, Kulkarni SK: Protective effect of Curcumin, the active principle of turmeric (Curcuma longa) in haloperidol-induced orofacial dyskinesia and associated behavioural, biochemical and neurochemical changes in rat brain. Pharmacol Biochem Behav 2008, 88, 511-522.
Kulkarni SK, Bhutani MK, Bishnoi M: Antidepressant activity of curcumin: involvement of serotonin and dopamine system. Psychopharmacology 2008, 201, 435-442.
Bhutani MK, Bishnoi M, Kulkarni SK: Anti-depressant like effect of curcumin and its combination with piperine in unpredictable chronic stress-induced behavioral, biochemical and neurochemical changes. Pharmacol Biochem Behav 2009, 92, 39-43.
Li YC, Wang FM, Pan Y, Qiang LQ, Cheng G, Zhang WY, Kong LD: Antidepressant-like effects of curcumin on serotonergic receptorcoupled AC-cAMP pathway in chronic unpredictable mild stress of rats. Prog Neuropsychopharmacol Biol Psychiatry 2009, 33, 435-449.
File SE, Wardill AG: Validity of head-dipping as a measure of exploration in a modified hole-board. Psychopharmacologia 1975a, 44, 53-59.
File SE, Wardill AG: The reliability of the hole-board apparatus. Psychopharmacologia 1975b, 44, 47-51.
Sedlak J, Lindsay RH: Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman’s Reagent. Anal Biochem 1968, 25, 192-205.
Habig WH, Pabst MJ, Jakoby WB: Glutathione S-transferases; the first enzymatic step in mercapturic acid formation. J Biol Chem 1974, 249, 7130-7139.
Goth L: A simple method for determination of serum catalase activity and revision of reference range. Clin Chim Acta 1991, 196, 143-152.
Okhawa H, Ohishi N, Yagi K: Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 1979, 95, 351-358.
Crawley JN: Exploratory behavior models of anxiety in mice. Neurosci Biobehav Rev 1985, 9, 37-44.
Takeda H, Tsuji M, Matsumiya: Changes in head-dipping behavior in the hole-board test reflect the anxiogenic and/or anxiolytic state in mice. Eur J Pharmacol 1998, 350, 21-29.
Brown GR, Nemes C: The exploratory behaviour of rats in the holeboard apparatus: Is head-dipping a valid measure of neophilia? Behav Procc 2008, 78, 442-448.
Sapolsky RM, Krey LC, McEwen BS. The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr Rev 1986; 7, 284-301.
Marin MT, Cruz FC, Planeta CS: Chronic restraint or variable stresses differently affect the behavior, corticosterone secretion and body weight in rats. Physiol Behav 2007, 90, 29-35.
Xu Y, Ku BS, Tie L, Yao H, Jiang W, Ma X, Li X: Curcumin reverses the effect of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB. Brain Res 2006, 1122, 56-64.
Xu Y, Lin D, Li S, Li G, Shyamala SG, Barish PA, Vernon MM, Pan J, Ogle W: Curcumin reverses impaired cognition and neuronal plasticity induced by chronic stress. Neuropharmacology 2009, 57, 463-471.
Kumar A, Dogra S, Prakash A: Protective effects of curcumin (Curcuma longa), against aluminium toxicity: Possible behavioral and biochemical alterations in rats. Behav Brain Res 2009, 205, 384-390.
Awasthi H, Tota S, Hanif K, Nath C, Shukla R: Protective effect of curcumin against intracerebral streptozotocin induced impairment in memory and cerebral blood flow. Life Sci 2010, 86, 87-94.
Yadav RS, Sankhwar ML, Shukla RK, Chandra R, Pant AB, Islam F, Khanna VK: Attenuation of arsenic neurotoxicity by curcumin in rats. Toxicol Appl Pharmacol 2009, 240, 367-376.
Sethi P, Jyoti A, Hussain E, Sharma D: Curcumin attenuates aluminiuminduced functional neurotoxicity in rats. Pharmacol Biochem Beh 2009, 93, 31-39.
Shukla PK, Khanna VK, Ali MM, Khan MY, Srimal RC: Anti-ischemic effect of curcumin in rat brain. Neurochem Res 2008, 33, 1036-1043.
Kliethermes CL, Crabbe JC: Pharmacological and genetic influences on hole-board behaviors in mice. Pharmacol Biochem Behav 2006, 85, 57-65.
Arrias-Carrion O, Poppel E. Dopamine, learning and reward-seeking behavior: Acta Neurobiol Exp 2007, 67, 481-488.
Morita T, Sonoda R, Nakato K, Koshiya K, Wanibuchi F, Yamaguchi T: Phencyclidine-induced abnormal behaviors in rats as measured by the hole board apparatus. Psychopharmacology (Berl) 2000, 148, 281- 288.
Takeda H, Tsuji M, Ikoshi H, Yamada T, Masuya J, Iimori M, Matsumiya T: Effects of a 5-HT7 receptor antagonist DR4004 on the exploratory behavior in a novel environment and on brain monoamine dynamics in mice. Eur J Pharmacol 2005, 518, 30-39.
Xu Y, Ku BS, Yao HY, Lin YH, Ma X, Zhang YH, Li XJ: Antidepressant effects of curcumin in the forced swim test and olfactory bulbectomy models of depression in rats. Pharmacol Biochem Behav 2005, 82, 200- 206.
Nishimura A, Ueda S, Takeuchi Y, Sawada T, Kawata M: Age-related, decrease of serotonergic fibres and S-100 beta immunoreactivity in the rat dentate gyrus. Neuroreport 1995, 6, 1445-1448.
Gonzalez-Burgos I, Feria-Velasco A: Serotonin/dopamine interaction in memory formation. Review. Prog Brain Res 2008, 172, 603-623.
Wang R, Xu Y, Wu HL, Li YB, Li YH, Guo JB, Li XJ: The antidepressant effect of curcumin in the forced swimming test involve 5-HT1 and 5- HT-2 receptors. Eur J Pharmacol 2008, 578, 43-50.
Tsuji M, Takeda H, Matsumiya T: Different effects of 5-HT1A receptor agonists and benzodiazepine anxiolytics on the emotional state of naïve and stressed mice: a study using the hole-board test. Psychopharmacology (Berl) 2000, 152, 157-166.
Aggarwal BB, Kumar A, Bharti AC: Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res 2003, 23, 363-398.
Aggarwal BB, Sundaram C, Malani N, Ichikawa H: Curcumin: the Indian solid gold. Adv Exp Med Biol 2007, 595, 1-75.
Singh S, Khar A: Biological effects of curcumin and its role in cancer chemoprevention and therapy. Anticancer Agents Med Chem 2006, 6, 259-270.
Sharma RA, Gesher AJ, Steward WP: Curcumin: the story so far. Eur J Cancer 2005, 41, 1955-1968.
Priyadarsini KI: Free radical reactions of curcumin in membrane models. Free Radic Biol Med 1997, 23, 838-843.
Motterlini R, Foresti R, Bassi R, Green CJ: Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress. Free Radic Biol Med 2000, 28, 1303-1312.
Awasthi S, Pandya U, Singhal SS, Lin JT, Thiviyanathan V, Seifert Jr WE, Awasthi YC, Ansari GA: Curcumin-glutahione interactions and the role of human glutathione S-transferase P1-1. Chem Biol Interactions 2000, 128, 19-38.
Balogun E, Hogue M, Gong P, Kileen P, Green CJ, Foresti R, Alam J, Motterlini R: Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive element. J Biochem 2003, 371, 887-895.
Iqbal M, Sharma SD, Okazaki Y, Fujisawa M, Okada S: Dietary supplementation of curcumin enhances antioxidant and phase II metabolizing enzymes in ddY male mice: possible role in protection against chemical carcinogenesis and toxicity. Pharmacol Toxicol 2003, 92, 33-38.
Rushworth SA, Ogborne RM, Charalambos CA, O’Connell MA: Role of protein kinase C delta in curcumin-induced antioxidant response element-mediated gene expression in human monocytes. Biochem Biophys Res Commun 2006, 341, 1007-1016.
Wei QY, Chen WF, Zhou B, Yang L, Liu ZL: Inhibition of lipid peroxidation and protein oxidation in rat liver mitochondria by curcumin and its analogues. Biochim Biophys Acta 2006, 1760, 70- 77.
Bhaumik S, Anjum R, Rangaraj N, Pardhasaradhi BV, Khar A: Curcumin mediated apoptosis in AK-5 tumor cells involves the production of reactive oxygen intermediates. FEBS Lett 1999, 456, 311-314.
Fang J, Lu J, Holmgren A: Thioredoxin reductase is irreversibly modified by curcumin: a novel molecular mechanism for its anticancer activity. J Biol Chem 2005, 280, 25284-25290.
Jung EM, Lim JH, Lee TJ, Park JW, Choi KS, Kwon TK: Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upregulation of death receptor 5 (DR5). Carcinogenesis 2005, 26, 1905- 1913.
Li H, van Berlo D, Shi T, Speit G, Knaapen AM, Borm PJ, Albrecht C, Schins RP: Curcumin protects against cytotoxic and inflammatory effects of quartz particles but causes oxidative DNA damage in a rat lung epithelial cell line. Toxicol Appl Pharmacol 2008, 227, 115-124.
Chen J, Wanming D, Zhang D, Liu Q, Kang J: Water-soluble antioxidants improve the antioxidant and anticancer activity of low concentrations of curcumin in human leukemia cells. Pharmazie 2005, 60, 57-61.
Kunwar A, Sandur SK, Krishna M, Priyadarsini KI: Curcumin mediates time and concentration dependent regulation of redox homeostasis leading to cytotoxicity in macrophage cells. Eur J Pharm 2009, 611, 8-16.
Tanwar V, Sachdeva J, Kishore K, Mittal R, Nag TC, Ray R, Kumari S, Arya DS: Dose-dependent actions of curcumin in experimentally induced myocardial necrosis: a biochemical, histopathological, and electron microscopic evidence. Cell Biochem Funct 2010, 28, 74-82.
Manikandan P, Sumitra M, Aishwarya S, Manohar BM, lokanadam B, Puvanakrishnan R: Curcumin modulates free radical quenching in myocardial ischaemia in rats. Int J Bioch Cell Biol 2004, 36, 1967- 1980.
Gutowicz M, Chołojczyk M, Pyrzanowska J, Widy-Tyszkiewicz E, Barańczyk-Kuźma A: Wpływ kurkuminy na detoksykacyjne i antyoksydacyjne mechanizmy w wątrobie szczurow podczas starzenia (in Polish). Effect of curcumin on detoxicative and anti-oxidative mechanisms in rat’s liver during ageing. Med Wet 2008, 64, 955 957.
Reeta KH, Mehla J, Gupta YK: Curcumin is protective against phenytoin-induced cognitive impairment and oxidative stress in rats Brain Res 2009, 1301, 52-60.
Lavoie S, Chen Y, Dalton TP, Gysin R, Cuenod M, Steullet P, Do KQ: Curcumin, quercetin, and tBHQ modulate glutathione levels in mastrocytes and neurons: importance of the glutamate cysteine ligase modifier subunit. J Neurochem 2009, 108, 1410-1422.
Gupta YK, Briyal S, Sharma M: Protective effect of curcumin against kainic acid induced seizures and oxidative stress in rats. Indian J Physiol Pharmacol 2009, 53, 39-46.
El-Demerdash FM, Yousef MI, Radwan FM: Ameliorating effect of curcumin on sodium arsenite-induced oxidative damage and lipid peroxidation in different rat organs. Food Chem Toxicol 2009, 47, 249- 254.
Appiah-Opong R, Commandeur JN, Istyastono E, Bogaards JJ, Vermeulen NP: Inhibition of human glutathione S-transferases by curcumin and analogues. Xenobiotica 2009, 39, 302-311.
Ali MS, Mudagal MP, Goli D: Cardioprotective effect of tetrahydrocurcumin and rutin on lipid peroxides and antioxidants in experimentally induced myocardial infarction in rats. Pharmazie 2009, 64, 132-136.