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Effects of chlorogenic acid, caffeine, and coffee on behavioral and biochemical parameters of diabetic rats

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Abstract

Diabetes mellitus (DM) is associated with brain alterations that may contribute to cognitive dysfunctions. Chlorogenic acid (CGA) and caffeine (CA), abundant in coffee (CF), are natural compounds that have showed important actions in the brain. The present study aimed to evaluate the effect of CGA, CA, and CF on acetylcholinesterase (AChE), Na+, K+-ATPase, aminolevulinate dehydratase (δ-ALA-D) activities and TBARS levels from cerebral cortex, as well as memory and anxiety in streptozotocin-induced diabetic rats. Animals were divided into eight groups (n = 5–10): control; control/CGA 5 mg/kg; control/CA 15 mg/kg; control/CF 0.5 g/kg; diabetic; diabetic/CGA 5 mg/kg; diabetic/CA 15 mg/kg; and diabetic/CF 0.5 g/kg. Our results demonstrated an increase in AChE activity and TBARS levels in cerebral cortex, while δ-ALA-D and Na+, K+-ATPase activities were decreased in the diabetic rats when compared to control water group. Furthermore, a memory deficit and an increase in anxiety in diabetic rats were observed. The treatment with CGA and CA prevented the increase in AChE activity in diabetic rats when compared to the diabetic water group. CGA, CA, and CF intake partially prevented cerebral δ-ALA-D and Na+, K+-ATPase activity decrease due to diabetes. Moreover, CGA prevented diabetes-induced TBARS production, improved memory, and decreased anxiety. In conclusion, among the compounds studied CGA proved to be a compound which acts better in the prevention of brain disorders promoted by DM.

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References

  1. Gannon M (2001) Molecular genetic analysis of diabetes in mice. Trends Genet 17:S23–S28

    Article  CAS  PubMed  Google Scholar 

  2. Ahmed N, Thornalley PJ (2007) Advanced glycation endproducts: what is their relevance to diabetic complications? Diabetes Obes Metab 9:233–245. doi:10.1111/j.1463-1326.2006.00595.x

    Article  CAS  PubMed  Google Scholar 

  3. Gispen WH, Biessels GJ (2000) Cognition and synaptic plasticity in diabetes mellitus. Trends Neurosci 23:542–549

    Article  CAS  PubMed  Google Scholar 

  4. Schmatz R, Mazzanti CM, Spanevello R, Stefanello N, Gutierres J, Correa M, da Rosa MM, Rubin MA, Chitolina Schetinger MR, Morsch VM (2009) Resveratrol prevents memory deficits and the increase in acetylcholinesterase activity in streptozotocin-induced diabetic rats. Eur J Pharmacol 610:42–48. doi:10.1016/j.ejphar.2009.03.032

    Article  CAS  PubMed  Google Scholar 

  5. Pari L, Murugan P (2007) Tetrahydrocurcumin prevents brain lipid peroxidation in streptozotocin-induced diabetic rats. J Med Food 10:323–329. doi:10.1089/jmf.2006.058

    Article  CAS  PubMed  Google Scholar 

  6. Franzon R, Chiarani F, Mendes RH, Bello-Klein A, Wyse AT (2005) Dietary soy prevents brain Na+, K(+)-ATPase reduction in streptozotocin diabetic rats. Diabetes Res Clin Pract 69:107–112. doi:10.1016/j.diabres.2004.11.010

    Article  CAS  PubMed  Google Scholar 

  7. Rocha JBT, Saraiva RA, Garcia SC, Gravina FS, Nogueira CW (2012) Aminolevulinate dehydratase (δ-ALA-D) as marker protein of intoxication with metals and other pro-oxidant situations. Toxicol Res 1:85–102. doi:10.1039/C2TX20014G

    Article  CAS  Google Scholar 

  8. Schmatz R, Perreira LB, Stefanello N, Mazzanti C, Spanevello R, Gutierres J, Bagatini M, Martins CC, Abdalla FH, da Silva Daci, Serres J, Zanini D, Vieira JM, Cardoso AM, Schetinger MR, Morsch VM (2012) Effects of resveratrol on biomarkers of oxidative stress and on the activity of delta aminolevulinic acid dehydratase in liver and kidney of streptozotocin-induced diabetic rats. Biochimie 94:374–383. doi:10.1016/j.biochi.2011.08.005

    Article  CAS  PubMed  Google Scholar 

  9. Clausen T, Van Hardeveld C, Everts ME (1991) Significance of cation transport in control of energy metabolism and thermogenesis. Physiol Rev 71:733–774

    CAS  PubMed  Google Scholar 

  10. Santini SA, Cotroneo P, Marra G, Manto A, Giardina B, Mordente A, Greco AV, Martorana GE, Magnani P, Ghirlanda G (1996) Na+/K+-ATPase impairment and experimental glycation: the role of glucose autoxidation. Free Radic Res 24:381–389

    Article  CAS  PubMed  Google Scholar 

  11. Soreq H, Seidman S (2001) Acetylcholinesterase: new roles for an old actor. Nat Rev Neurosci 2:294–302. doi:10.1038/35067589

    Article  CAS  PubMed  Google Scholar 

  12. Spanevello R, Mazzanti CM, Schmatz R, Bagatini M, Stefanello N, Correa M, Kaizer R, Maldonado P, Mazzanti A, Graca DL, Martins TB, Danesi C, Morsch VM, Schetinger MR (2009) Effect of vitamin E on ectonucleotidase activities in synaptosomes and platelets and parameters of oxidative stress in rats experimentally demyelinated. Brain Res Bull 80:45–51. doi:10.1016/j.brainresbull.2009.05.015

    Article  CAS  PubMed  Google Scholar 

  13. van Dam RM (2006) Coffee and type 2 diabetes: from beans to beta-cells. Nutr Metab Cardiovasc Dis 16:69–77. doi:10.1016/j.numecd.2005.10.003

    Article  PubMed  Google Scholar 

  14. Greenberg JA, Boozer CN, Geliebter A (2006) Coffee, diabetes, and weight control. Am J Clin Nutr 84:682–693

    CAS  PubMed  Google Scholar 

  15. McCarty MF (2005) A chlorogenic acid-induced increase in GLP-1 production may mediate the impact of heavy coffee consumption on diabetes risk. Med Hypotheses 64:848–853. doi:10.1016/j.mehy.2004.03.037

    Article  CAS  PubMed  Google Scholar 

  16. Cho AS, Jeon SM, Kim MJ, Yeo J, Seo KI, Choi MS, Lee MK (2010) Chlorogenic acid exhibits anti-obesity property and improves lipid metabolism in high-fat diet-induced-obese mice. Food Chem Toxicol 48:937–943. doi:10.1016/j.fct.2010.01.003

    Article  CAS  PubMed  Google Scholar 

  17. Zang LY, Cosma G, Gardner H, Castranova V, Vallyathan V (2003) Effect of chlorogenic acid on hydroxyl radical. Mol Cell Biochem 247:205–210

    Article  PubMed  Google Scholar 

  18. dos Santos MD, Almeida MC, Lopes NP, de Souza GE (2006) Evaluation of the anti-inflammatory, analgesic and antipyretic activities of the natural polyphenol chlorogenic acid. Biol Pharm Bull 29:2236–2240

    Article  PubMed  Google Scholar 

  19. Li Y, Shi W, Zhou Y, Hu X, Song C, Ma H, Wang C (2008) Neuroprotective effects of chlorogenic acid against apoptosis of PC12 cells induced by methylmercury. Environ Toxicol Pharmacol 26:13–21. doi:10.1016/j.etap.2007.12.008

    Article  PubMed  Google Scholar 

  20. Nehlig A, Daval JL, Debry G (1992) Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res Brain Res Rev 17:139–170

    Article  CAS  PubMed  Google Scholar 

  21. Karthikesan K, Pari L, Menon VP (2010) Combined treatment of tetrahydrocurcumin and chlorogenic acid exerts potential antihyperglycemic effect on streptozotocin-nicotinamide-induced diabetic rats. Gen Physiol Biophys 29:23–30

    Article  CAS  PubMed  Google Scholar 

  22. Schnedl WJ, Ferber S, Johnson JH, Newgard CB (1994) STZ transport and cytotoxicity. Specific enhancement in GLUT2-expressing cells. Diabetes 43:1326–1333

    Article  CAS  PubMed  Google Scholar 

  23. Guerra GP, Mello CF, Sauzem PD, Berlese DB, Furian AF, Tabarelli Z, Rubin MA (2006) Nitric oxide is involved in the memory facilitation induced by spermidine in rats. Psychopharmacology (Berl) 182:150–158. doi:10.1007/s00213-006-0376-5

    Article  Google Scholar 

  24. Frussa-Filho R, Barbosa-Junior H, Silva RH, Da Cunha C, Mello CF (1999) Naltrexone potentiates the anxiolytic effects of chlordiazepoxide in rats exposed to novel environments. Psychopharmacology 147:168–173

    Article  CAS  PubMed  Google Scholar 

  25. Rubin MA, Albach CA, Berlese DB, Bonacorso HG, Bittencourt SR, Queiroz CM, Maixner AE, Mello CF (2000) Anxiolytic-like effects of 4-phenyl-2-trichloromethyl-3H-1, 5-benzodiazepine hydrogen sulfate in mice. Braz J Med Biol Res 33:1069–1073

    Article  CAS  PubMed  Google Scholar 

  26. Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  PubMed  Google Scholar 

  27. Sassa S (1982) Delta-aminolevulinic acid dehydratase assay. Enzyme 28:133–145

    CAS  PubMed  Google Scholar 

  28. Wyse AT, Streck EL, Barros SV, Brusque AM, Zugno AI, Wajner M (2000) Methylmalonate administration decreases Na+, K+-ATPase activity in cerebral cortex of rats. Neuroreport 11:2331–2334

    Article  CAS  PubMed  Google Scholar 

  29. Carvalho FB, Mello CF, Marisco PC, Tonello R, Girardi BA, Ferreira J, Oliveira MS, Rubin MA (2012) Spermidine decreases Na(+), K(+)-ATPase activity through NMDA receptor and protein kinase G activation in the hippocampus of rats. Eur J Pharmacol 684:79–86. doi:10.1016/j.ejphar.2012.03.046

    Article  CAS  PubMed  Google Scholar 

  30. Fiske CH, Subbarow Y (1925) The colorimetric determination of phosphorous. J Biol Chem 66:375–400

    CAS  Google Scholar 

  31. Nagy A, Delgado-Escueta AV (1984) Rapid preparation of synaptosomes from mammalian brain using nontoxic isoosmotic gradient material (Percoll). J Neurochem 43:1114–1123

    Article  CAS  PubMed  Google Scholar 

  32. Ellman GL, Courtney KD, Andres V Jr, Feather-Stone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95

    Article  CAS  PubMed  Google Scholar 

  33. Rocha JBT, Emanuelli T, Pereira ME (1993) Effects of early under nutrition on kinetic parameters of brain acetylcholinesterase from adult rats. Acta Neurobiol Exp 53:431–437

    CAS  Google Scholar 

  34. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding. Anal Biochem 72:248–254

    Article  CAS  PubMed  Google Scholar 

  35. Bonnefont-Rousselot D (2002) Glucose and reactive oxygen species. Curr Opin Clin Nutr Metab Care 5:561–568

    Article  CAS  PubMed  Google Scholar 

  36. Folmer V, Soares JC, Gabriel D, Rocha JB (2003) A high fat diet inhibits delta-aminolevulinate dehydratase and increases lipid peroxidation in mice (Mus musculus). J Nutr 133:2165–2170

    CAS  PubMed  Google Scholar 

  37. Baynes JW, Thorpe SR (1999) Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes 48:1–9

    Article  CAS  PubMed  Google Scholar 

  38. Shahidi F, Chandrasekara A (2010) Hydroxycinnamates and their in vitro and in vivo antioxidant activities. Phytochem Rev 9:147–170. doi:10.1007/s11101-009-9142-8

    Article  CAS  Google Scholar 

  39. Shi X, Dalal NS, Jain AC (1991) Antioxidant behaviour of caffeine: efficient scavenging of hydroxyl radicals. Food Chem Toxicol 29:1–6

    Article  CAS  PubMed  Google Scholar 

  40. Fan Y, Hu J, Li J, Yang Z, Xin X, Wang J, Ding J, Geng M (2005) Effect of acidic oligosaccharide sugar chain on scopolamine-induced memory impairment in rats and its related mechanisms. Neurosci Lett 374:222–226. doi:10.1016/j.neulet.2004.10.063

    Article  CAS  PubMed  Google Scholar 

  41. Szutowicz A, Tomaszewicz M, Bielarczyk H (1996) Disturbances of acetyl-CoA, energy and acetylcholine metabolism in some encephalopathies. Acta Neurobiol Exp 56:323–339

    CAS  Google Scholar 

  42. Kuhad A, Sethi R, Chopra K (2008) Lycopene attenuates diabetes-associated cognitive decline in rats. Life Sci 83:128–134. doi:10.1016/j.lfs.2008.05.013

    Article  CAS  PubMed  Google Scholar 

  43. Kamalakkannan N, Prince PS (2006) Antihyperglycaemic and antioxidant effect of rutin, a polyphenolic flavonoid, in streptozotocin-induced diabetic Wistar rats. Basic Clin Pharmacol Toxicol 98:97–103. doi:10.1111/j.1742-7843.2006.pto_241.x

    Article  CAS  PubMed  Google Scholar 

  44. Biessels GJ, Braun KP, de Graaf RA, van Eijsden P, Gispen WH, Nicolay K (2001) Cerebral metabolism in streptozotocin-diabetic rats: an in vivo magnetic resonance spectroscopy study. Diabetologia 44:346–353. doi:10.1007/s001250051625

    Article  CAS  PubMed  Google Scholar 

  45. Roriz-Filho JS, Sa-Roriz TM, Rosset I, Camozzato AL, Santos AC, Chaves ML, Moriguti JC, Roriz-Cruz M (2009) (Pre)diabetes, brain aging, and cognition. Biochim Biophys Acta 1792:432–443. doi:10.1016/j.bbadis.2008.12.003

    Article  CAS  Google Scholar 

  46. Gasparini L, Xu H (2003) Potential roles of insulin and IGF-1 in Alzheimer’s disease. Trends Neurosci 26:404–406. doi:10.1016/S0166-2236(03)00163-2

    Article  CAS  PubMed  Google Scholar 

  47. Kaizer RR, Correa MC, Spanevello RM, Morsch VM, Mazzanti CM, Goncalves JF, Schetinger MR (2005) Acetylcholinesterase activation and enhanced lipid peroxidation after long-term exposure to low levels of aluminum on different mouse brain regions. J Inorg Biochem 99:1865–1870. doi:10.1016/j.jinorgbio.2005.06.015

    Article  CAS  PubMed  Google Scholar 

  48. Rees T, Hammond PI, Soreq H, Younkin S, Brimijoin S (2003) Acetylcholinesterase promotes beta-amyloid plaques in cerebral cortex. Neurobiol Aging 24:777–787

    Article  CAS  PubMed  Google Scholar 

  49. Sudha S, Lakshmana MK, Pradhan N (1995) Changes in learning and memory, acetylcholinesterase activity and monoamines in brain after chronic carbamazepine administration in rats. Epilepsia 36:416–422

    Article  CAS  PubMed  Google Scholar 

  50. Grisaru D, Sternfeld M, Eldor A, Glick D, Soreq H (1999) Structural roles of acetylcholinesterase variants in biology and pathology. Eur J Biochem 264:672–686

    Article  CAS  PubMed  Google Scholar 

  51. Can OD, Ozturk Y, Ozkay UD (2011) Effects of insulin and St. John’s Wort treatments on anxiety, locomotory activity, depression, and active learning parameters of streptozotocin-diabetic rats. Planta Med 77:1970–1976. doi:10.1055/s-0031-1280129

    Article  CAS  PubMed  Google Scholar 

  52. Rajashree R, Kholkute SD, Goudar SS (2011) Effects of duration of diabetes on behavioural and cognitive parameters in streptozotocin-induced juvenile diabetic rats. Malays J Med Sci 18:26–31

    PubMed Central  PubMed  Google Scholar 

  53. Gomez R, Barros HM (2003) Clonazepam increases in vivo striatal extracellular glucose in diabetic rats after glucose overload. Pharmacol Biochem Behav 76:443–450

    Article  CAS  PubMed  Google Scholar 

  54. Antony S, Kumar TP, Kuruvilla KP, George N, Paulose CS (2010) Decreased GABA receptor binding in the cerebral cortex of insulin induced hypoglycemic and streptozotocin induced diabetic rats. Neurochem Res 35:1516–1521. doi:10.1007/s11064-010-0210-7

    Article  CAS  PubMed  Google Scholar 

  55. Cauli O, Morelli M (2005) Caffeine and the dopaminergic system. Behav Pharmacol 16:63–77

    Article  CAS  PubMed  Google Scholar 

  56. Kardos J, Blandl T (1994) Inhibition of a gamma aminobutyric acid A receptor by caffeine. Neuroreport 5:1249–1252

    Article  CAS  PubMed  Google Scholar 

  57. Bouayed J, Rammal H, Dicko A, Younos C, Soulimani R (2007) Chlorogenic acid, a polyphenol from Prunus domestica (Mirabelle), with coupled anxiolytic and antioxidant effects. J Neurol Sci 262:77–84. doi:10.1016/j.jns.2007.06.028

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors thank the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Fundação de Amparo à Pesquisa do Rio Grande do Sul (FAPERGS) for the research fellowships, FINEP-IBNET and INCT for Excitoxicity and neuroprotection.

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Authors and Affiliations

  1. Graduate Program in Biological Sciences: Toxicological Biochemistry, Center of Natural and Exact Sciences, Federal University of Santa Maria, University Campus, Camobi, Santa Maria, RS, 97105-900, Brazil

    Naiara Stefanello, Roberta Schmatz, Luciane Belmonte Pereira, Maribel A. Rubin, João Batista Teixeira da Rocha, Graziela Facco, Maria Ester Pereira, Marília Valvassori Rodrigues, Fabiano Barbosa Carvalho, Michelle Melgarejo da Rosa, Jessie Martins Gutierres, Andréia Machado Cardoso, Vera Maria Morsch & Maria Rosa Chitolina Schetinger

  2. Laboratory Clinical Veterinary (LACVet), Federal University of Santa Maria, University Campus, Camobi, Santa Maria, RS, 97105-900, Brazil

    Cinthia Melazzo de Andrade Mazzanti

  3. Department of Life Sciences, University of Trieste, via L. Giorgieri 1, 34127, Trieste, Italy

    Sabina Passamonti

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  1. Naiara Stefanello
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  2. Roberta Schmatz
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  3. Luciane Belmonte Pereira
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  4. Maribel A. Rubin
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Correspondence to Luciane Belmonte Pereira or Maria Rosa Chitolina Schetinger.

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Stefanello, N., Schmatz, R., Pereira, L.B. et al. Effects of chlorogenic acid, caffeine, and coffee on behavioral and biochemical parameters of diabetic rats. Mol Cell Biochem 388, 277–286 (2014). https://doi.org/10.1007/s11010-013-1919-9

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