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Involvement of PPAR-gamma in curcumin-mediated beneficial effects in experimental dementia

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Abstract

The present study was undertaken to investigate the possible mechanism of curcumin-mediated beneficial effects in memory deficits associated with experimental dementia. Dementia was induced in Swiss albino mice by administrating streptozotocin (3 mg kg−1) intracerebroventricularly on first and third day. Morris water maze test was employed to assess learning and memory of the animals. Biochemical analysis of brain homogenate was performed to assess brain acetyl cholinesterase (AChE) activity and total oxidative stress. Streptozotocin (STZ) produced a significant decrease in water maze performance of mice indicative of impairment in spatial reference memory. Curcumin (20 mg/kg p.o. daily for 14 days) successfully attenuated STZ-induced memory deficits. Higher levels of brain AChE activity and oxidative stress were observed in STZ-treated animals, which were significantly attenuated by curcumin. Furthermore, the noted beneficial effect of curcumin on STZ-induced dementia was significantly abolished by pretreatment with PPAR-γ receptor antagonist bisphenol-A-diglycidyl ether, i.e., BADGE (30 mg/kg intraperitoneally (i.p.)). It may be concluded that the beneficial effects of curcumin are mediated through the activation of PPAR-γ receptors.

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References

  • Agrawal R, Mishra B, Tyagi E, Nath C, Shukla R (2009) Effect of curcumin on brain insulin receptors and memory functions in STZ (ICV) induced dementia model of rat. Pharmacol Res 61:247–252

    Article  PubMed  CAS  Google Scholar 

  • Ahmed T, Gilani AH (2009) Inhibitory effect of curcuminoids on acetylcholinesterase activity and attenuation of scopolamine-induced amnesia may explain medicinal use of turmeric in Alzheimer's disease. Pharmacol Biochem Behav 91(4):554–559

    Article  CAS  PubMed  Google Scholar 

  • Balasubramanian K (2006) Molecular orbital basis for yellow curry spice curcumin's prevention of Alzheimer's disease. J Agric Food Chem 54(10):3512–3520

    Article  CAS  PubMed  Google Scholar 

  • Baum L, Alex NG (2004) Curcumin interaction with copper and iron suggests one possible mechanism of action in Alzheimer’s disease animal models. J Alzheimer’s Dis 6:367–377

    CAS  Google Scholar 

  • Begum AN, Jones MR, Lim GP, Morihara T, Kim P, Heath DD, Rock CL, Pruitt MA, Yang F, Hudspeth B, Hu S, Faull KF, Teter B, Cole GM, Frautschy SA (2008) Curcumin structure-function, bioavailability, and efficacy in models of neuroinflammation and Alzheimer's disease. J Pharmacol Exp Ther 326(1):196–208

    Article  CAS  PubMed  Google Scholar 

  • Beutler E, Duron O, Kelly BM (1963) Improved methods for determination of blood glutathione. J Lab Clin Med 61:882–888

    CAS  PubMed  Google Scholar 

  • Braak H, Del Tredici K, Schultz C, Braak E (2000) Vulnerability of selective neuronal types to Alzheimer’s disease. Ann N Y Acad Sci 924:53–61

    CAS  PubMed  Google Scholar 

  • Butterfield DA (2004) Proteomics: a new approach to investigate oxidative stress in Alzheimer’s disease brain. Brain Res 1000:1–7

    Article  CAS  PubMed  Google Scholar 

  • Cuzzocrea S, Pisano B, Dugo L, Ianaro A, Patel NSA, Di Paola R, Genovese T, Chatterjee PK, Di Rosa M, Caputi AP, Thiemermann C (2004) Rosiglitazone, a ligand of the peroxisome proliferator-activated receptor-γ, reduces acute inflammation. Eur J Pharmacol 483(1):79–93

    Article  CAS  PubMed  Google Scholar 

  • De la Monte SM, Tong M, Lester-Coll N, Plater M Jr, Wands JR (2006) Therapeutic rescue of neurodegeneration in experimental type 3 diabetes: relevance to Alzheimer’s disease. J Alzheimer’s disease 10(1):89–109

    Google Scholar 

  • Deplanque D (2004) Cell protection through PPAR nuclear receptor activation. Therapie 59(1):25–29

    Article  PubMed  Google Scholar 

  • Dhingra D, Parle M, Kulkarni SK (2003) Comparative brain cholinesterase inhibiting activity of Glycyrrhiza glabra, Myristica fragrans, ascorbic acid and metrifonate in mice. J Med Food 9:281–283

    Article  Google Scholar 

  • Di Santo R, Costi R, Artico M, Ragno R, Greco G, Novellino E et al (2005) Design, synthesis and biological evaluation of heteroaryl diketohexenoic and diketobutanoic acids as HIV-1 integrase inhibitors endowed with antiretroviral activity. Farmaco 60:409–417

    Article  PubMed  CAS  Google Scholar 

  • Diab A, Deng C, Smith JD, Hussain RZ, Phanavanh B, Lovett- Racke AE, Drew PD, Racke MK (2002) Peroxisome proliferator-activated receptor-γ agonist 15-deoxy-Delta (12, 14)-prostaglandin J (2) ameliorates experimental autoimmune encephalomyelitis. J Immunol 168:2508–2515

    CAS  PubMed  Google Scholar 

  • Ellman GL, Courtney KD, Valentino A, Featherstone RM (1961) A new and rapid olometric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    Article  CAS  PubMed  Google Scholar 

  • Feillet-Coudray C, Rock E, Coudray C, Grzelkowska K, Azais-Braesco V, Dardevet D, Mazur A (1999) Lipid peroxidation and antioxidant status in experimental diabetes. Clin Chim Acta 284:31–43

    Article  CAS  PubMed  Google Scholar 

  • Francis PT, Palmer AM, Snape M, Wilcock GK (1999) The cholinergic hypothesis of Alzheimer’s disease: a review of progress. J Neurol Neurosurg Psychiatry 66:137–147

    Article  CAS  PubMed  Google Scholar 

  • Fratiglioni L, Winblad B, Strauss EV (2007) Prevention of Alzheimer’s disease and dementia. Major findings from the Kungsholmen Project. Physiol Behav 92:98–104

    Article  CAS  PubMed  Google Scholar 

  • Fukui K, Omoi NO, Hayasaka T, Shinnkai T, Suzuki S, Abe K (2002) Cognitive impairment of rats caused by oxidative stress and aging, and its prevention by Vitamin E. Ann N Y Acad Sci 959:272–284

    Google Scholar 

  • Ganguli M, Chandra V, Kamboh MI (2000) Apolipoprotein E polymorphism and Alzheimer’s disease: the Indo-US Cross-National Dementia Study. Neurology 57:824–830

    Article  CAS  Google Scholar 

  • Gary EG, Hsueh-Meei H (2005) Oxidative stress in Alzheimer’s disease. Neurobiol Aging 26:575–578

    Article  CAS  Google Scholar 

  • Heneka MT, Landreth GE (2007) PPARS in brain. Biochim Biophys Acta 1771:1031–1045

    Article  CAS  Google Scholar 

  • Henke BR (2004) Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands and their therapeutic utility. Prog Med Chem 42:1–53

    Article  CAS  PubMed  Google Scholar 

  • Hong M, Lee VM (1997) Insulin and insulin-like growth factor-1 regulate tau phosphorylation in cultured human neurons. J Biol Chem 272(31):19547–19553

    Article  CAS  PubMed  Google Scholar 

  • Hoyer S, Muller D, Plaschke K (1994) Desensitization of brain insulin receptor: effect on glucose energy and related metabolism. J Neural Transmission 44(Suppl):259–268

    CAS  Google Scholar 

  • Ishida H, Takizawa M, Ozawa S, Nakamichi Y, Yamaguchi S, Katsuta NS (2004) Pioglitazone improves insulin secreatory capacity and prevents the loss of beta-cell mass in obese diabetic db/db mice: possible protection of beta cells from oxidative stress. Metabolism 53(4):488–494

    Article  CAS  PubMed  Google Scholar 

  • Ishrat T, Hoda MN, Khan MB, Yousuf S, Ahmad M, Khan MM, Ahmad A, Islam F (2009) Amelioration of cognitive deficits and neurodegeneration by curcumin in rat model of sporadic dementia of Alzheimer's type (SDAT). Eur Neuropsychopharmacol 19:636–647

    Article  CAS  PubMed  Google Scholar 

  • Isik AT, Celik T, Ulusoy G, Ongoru O, Elibol B, Doruk H, Bozoglu E, Kayir H, Mas MR, Akman S (2009) Curcumin ameliorates impaired insulin/IGF signaling and memory deficit in a streptozotocin-treated rat model. AGE 31:39–49

    Article  CAS  PubMed  Google Scholar 

  • Izzo AA, Capasso F (2007) Herbal medicines to treat Alzheimer’s disease. Trends Pharmacol Sci 28:47–48

    Article  CAS  PubMed  Google Scholar 

  • Jacob A, Wu R, Zhou M, Wang P (2007) Mechanism of the anti-inflammatory effect of curcumin: PPAR-gamma activation. PPAR Res 2007:89369

    PubMed  Google Scholar 

  • Jayesh BM, Arvind NP, Chitrang JT, Balaraman R (2005) Effect of Pioglitazone on L-NAME induced hypertension in diabetic rats. Vascular Pharmacology 43:260–266

    Article  CAS  Google Scholar 

  • Jing C, Ting AT, Seed B (1998) PPAR gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391:82–86

    Article  Google Scholar 

  • Juraj C (2007) PPAR-γ: therapeutic target for ischemic stroke. Trends Pharmacol Sci 28:243–249

    Google Scholar 

  • Kaur B, Singh N, Jaggi AS (2009) Exploring mechanism of pioglitazone induced memory restorative effect in experimental dementia. Fundamental Clin Pharmacol 23(5):557–566

    Article  CAS  Google Scholar 

  • Kuhad A, Chopra K (2007) Curcumin attenuates diabetic encephalopathy in rats: behavioral and biochemical evidences. Eur J Pharmacol 576:34–42

    Article  CAS  PubMed  Google Scholar 

  • Kumar A, Naidu PS, Seghal N, Padi SS (2007a) Effect of curcumin on intracerebroventricular colchicine-induced cognitive impairment and oxidative stress in rats. J Med Food 10(3):486–494

    Article  CAS  PubMed  Google Scholar 

  • Kumar P, Padi SS, Naidu PS, Kumar A (2007b) Possible neuroprotective mechanisms of curcumin in attenuating 3-nitropropionic acid-induced neurotoxicity. Methods Find Exp Clin Pharmacol 29(1):19–25

    Article  CAS  PubMed  Google Scholar 

  • Lannert H, Hoyer S (1998) Intracerebroventricular administration of streptozotocin causes long-term diminutions in learning and memory abilities and in cerebral energy metabolism in adult rats. Behav Neurosci 112:1199–1208

    Article  CAS  PubMed  Google Scholar 

  • Lim GP, Chu T, Yang F, Beech W, Frautschy SA, Cole GM (2001) The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J Neurosci 21:8370–8377

    CAS  PubMed  Google Scholar 

  • Lin J, Chen A (2008) Activation of peroxisome proliferator-activated receptor-gamma by curcumin blocks the signaling pathways for PDGF and EGF in hepatic stellate cells. Lab Invest 88(5):529–540

    Article  CAS  PubMed  Google Scholar 

  • Lowry OH, Rosebrough NJ, Far AL, Randall RJ (1951) Protein measurement with folin-phenol reagent. J Biol Chem 193:265–275

    CAS  PubMed  Google Scholar 

  • Mayer G, Nitsch R, Hoyer S (1990) Effects of changes in peripheral and cerebral glucose metabolism on locomotor activity, learning and memory in adult male rats. Brain Res 532:95–100

    Article  CAS  PubMed  Google Scholar 

  • Mishra S, Palanivelu K (2008) The effect of curcumin (turmeric) on Alzheimer’s disease: an overview. Ann Indian Acad Neurol 11:13–19

    Article  PubMed  Google Scholar 

  • McIntosh LJ, Trush MA, Troncoso JC (1997) Increased susceptibility of Alzheimer’s disease temporal cortex to oxygen free radical-mediated processes. Free Radic Biol Med 23:183–190

    Article  CAS  PubMed  Google Scholar 

  • Morris RGM (1984) Developments of a water maze procedure for studying spatial learning in the rats. J Neurosci Meth 11:47–60

    Article  CAS  Google Scholar 

  • Nandal S, Dhir A, Kuhad A, Sharma S, Chopra K (2009) Curcumin potentiates the anti-inflammatory activity of cyclooxygenase inhibitors in the cotton pellet granuloma pouch model. Methods Find Exp Clin Pharmacol 31(2):89–93

    Article  CAS  PubMed  Google Scholar 

  • Okhawa H, Ohishi N, Yagi K (1979) Assay of lipid peroxides in animals tissue by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  Google Scholar 

  • Packard MG, Teather L, Bazan NG (1996) Effect of intra-striated injections of platelet-activating factor and PAF antagonist BN 52021 on memory. Neurobiol Learn Mem 66:176–182

    Article  CAS  PubMed  Google Scholar 

  • Pan Rui QIU, Sheng LU Da-xiang, Jun DONG (2008) Curcumin improves learning and memory ability and its neuroprotective mechanism in mice. Chin Med J 121(9):832–839

    CAS  PubMed  Google Scholar 

  • Park SY, Kim HS, Cho EK, Kwon BY, Phark S, Hwang KW, Sul D (2008) Curcumin protected PC12 cells against beta-amyloid-induced toxicity through the inhibition of oxidative damage and tau hyperphosphorylation. Food Chem Toxicol 46(8):2881–2887

    Article  CAS  PubMed  Google Scholar 

  • Parle M, Singh N (2004) Animal models for testing memory. Asia Pacific J Pharmacol 16:101–120

    Google Scholar 

  • Parle M, Singh N (2007) Reversal of memory deficits by atorvastatin and simvastatin in rats. Yakugaku Zasshi 127:1125–1137

    Article  CAS  PubMed  Google Scholar 

  • Pathan AR, Viswanad B, Sonkusare SK, Ramarao P (2006) Chronic administration of pioglitazone attenuates intracerebroventricular streptozotocin induced-memory impairment in rats. Life Sci 79:2209–2216

    Article  CAS  PubMed  Google Scholar 

  • Pathan AR, Gaikwad AB, Viswanad B, Ramarao P (2008) Rosiglitazone attenuates the cognitive deficits induced by high fat diet feeding in rats. Eur J Pharmacol 589(1–3):176–179

    Article  CAS  PubMed  Google Scholar 

  • Plassman BL, Langa KM, Fisher GG, Heeringa SG, Weir DR, Ofstedal MB et al (2007) Prevalence of dementia in the United States: the aging, demographics, and memory study. Neuroepidemiology 29:125–132

    Article  CAS  PubMed  Google Scholar 

  • Rajeswari A (2006) Curcumin protects mouse brain from oxidative stress caused by 1 methyl 4-phenyl-1, 2, 3, 6-tetrahydro pyridine. Eur rev Med Pharmacol Sci 10:157–161

    CAS  PubMed  Google Scholar 

  • Reagan LP, Magarinos AM, Yee DK, Swzeda LI, Van Bueren A, McCall AL, McEwen BS (2000) Oxidative stress and HNE conjugation of GLUT 3 are increased in the hippocampus of diabetic rats subjected to stress. Brain Res 862:292–300

    Article  CAS  PubMed  Google Scholar 

  • Ricote M, Huang JT, Welch JS, Glass CK (1999) The peroxisome proloferator receptor gamma as a regulator of monocyte/macrophage function. J Leukoc Biol 66:733–739

    CAS  PubMed  Google Scholar 

  • Sakurada T, Sakurada S, Katsuyama S, Sakurada C, No KT, Terenius L (1999) Noceceptin(1-7) antagonizes noceceptin induced hyperalgesia in mice. British J Pharmacol 128:941–944

    Article  CAS  Google Scholar 

  • Salkovic-Petrisic M, Hoyer S (2007) Central insulin resistance as a trigger for sporadic Alzheimer-like pathology: an experimental approach. J Neural Transm Suppl 72:217–233

    Article  CAS  PubMed  Google Scholar 

  • Sharma M, Gupta YK (2001) Intracerebroventricular injection of Streptozotocin in rats produces both oxidative stress in the brain and cognitive impairment. Life Sci 68:1021–1129

    Article  CAS  PubMed  Google Scholar 

  • Sharma B, Singh N, Singh M (2008a) Modulation of celecoxib and streptozotocin induced experimental dementia of Alzheimer’s disease type by pitavastatin and donepezil. J Psychopharmacol 22(2):162–171

    Article  CAS  PubMed  Google Scholar 

  • Sharma B, Singh N, Singh M, Jaggi AS (2008b) Exploitation of HIV protease inhibitor Indinavir as a memory restorative agent in experimental dementia. Pharmacol Biochem Behav 89(4):535–545

    Article  CAS  PubMed  Google Scholar 

  • Shi M, Cai Q, Yao L, Mao Y, Ming Y, Ouyang G (2006) Antiproliferation and apoptosis induced by curcumin in human ovarian cancer cells. Cell Boil Int 30:221–226

    Article  CAS  Google Scholar 

  • Shishodia S, Singh T, Chaturvedi MM (2007) Modulation of transcription factors by curcumin. Adv Exp Med Biol 595:127–148

    Article  PubMed  Google Scholar 

  • Shoham S, Bejar C, Kovalev E, Weinstock M (2003) Intracerebroventricular injection of streptozotocin causes neurotoxicity to myelin that contributes to spatial memory deficits in rats. Exp Neurol 184:1043–1052

    Article  CAS  PubMed  Google Scholar 

  • Shoham S, Bejar C, Kovalev E, Schorer-Apelbaum D, Weinstock M (2007) Ladostigil prevents gliosis, oxidative-nitrative stress and memory deficits induced by intracerebroventricular injection of streptozotocin in rats. Neuropharmacology 52:836–843

    Article  CAS  PubMed  Google Scholar 

  • Smith KJ, Kapoor R, Felts PA (1999) Demyelination: the role of reactive oxygen and nitrogen species. Brain Patho 9:69–92

    Article  CAS  Google Scholar 

  • Srinivasan K, Patole PS, Kaul CL, Ramarao P (2004) Reversal of glucose intolerance by Pioglitazone in high fat diet-fed rats. Methods Find Exp Clin Pharmacol 26:327–333

    Article  CAS  PubMed  Google Scholar 

  • Thomas D, Michael TH, Magdalena S, Jhonnes D, Jorg BS (2004) Protection by Pioglitazone in the MPTP model of Parkinson’s disease correlates with IkB induction and block of NFkB and INOS activation. J Neurochem 88:494–501

    Google Scholar 

  • Voss G, Sachsse K (1970) Red cell and plasma cholinesterase activities in microsamples of human and animal blood determined simultaneously by a modified acetylthiocholine-DTNB procedure. Toxicol Appl Pharmacol 16:764–772

    Google Scholar 

  • Wright HM, Clish CB, Mikami T, Hauser S, Yanagi K, Hiramatsu R, Serhan CN, Spiegelman BM (2000) A synthetic antagonist for the peroxisome proliferator-activated receptor gamma inhibits adipocyte differentiation. J Biol Chem 275:1873–1877

    Article  CAS  PubMed  Google Scholar 

  • Xu Y, Ku B, Tie L, Yao H, Jiang W, Ma X et al (2006) Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB. Brain Res 1122:56–64

    Article  CAS  PubMed  Google Scholar 

  • Zhou B, Teramukai S, Fukushima M (2007) Prevention and treatment of dementia or Alzheimer's disease by statins: a meta-analysis. Dement Geriatr Cogn Disord 23:194–201

    Article  PubMed  CAS  Google Scholar 

  • Zhu YG, Chen XC, Chen ZZ, Zeng YQ, Shi GB, Su YH et al (2004) Curcumin protects mitochondria from oxidative damage and attenuates apoptosis in cortical neurons. Acta Pharmacol Sin 25:1606–1612

    CAS  PubMed  Google Scholar 

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Acknowledgments

The authors would like to acknowledge Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala for providing technical facilities.

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  1. Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala, Punjab, India, 147002

    Puneet Rinwa, Baljinder Kaur, Amteshwar Singh Jaggi & Nirmal Singh

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  1. Puneet Rinwa
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Correspondence to Nirmal Singh.

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Rinwa, P., Kaur, B., Jaggi, A.S. et al. Involvement of PPAR-gamma in curcumin-mediated beneficial effects in experimental dementia. Naunyn-Schmied Arch Pharmacol 381, 529–539 (2010). https://doi.org/10.1007/s00210-010-0511-z

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