Metabolic Brain Disease

, Volume 33, Issue 5, pp 1551–1562 | Cite as

Southern Brazilian native fruit shows neurochemical, metabolic and behavioral benefits in an animal model of metabolic syndrome

  • Pathise Souto Oliveira
  • Vitor Clasen Chaves
  • Mayara Sandrielly Pereira Soares
  • Natália Pontes Bona
  • Lorenço Torres Mendonça
  • Fabiano Barbosa Carvalho
  • Jessié Martins Gutierres
  • Flávia Aleixo Vasconcellos
  • Marcia Vizzotto
  • Andriele Vieira
  • Roselia Maria Spanevello
  • Flávio Henrique Reginatto
  • Claiton Leoneti Lencina
  • Francieli Moro StefanelloEmail author
Original Article


In this work, we evaluated the effects of Psidium cattleianum (Red Type) (PcRT) fruit extract on metabolic, behavioral, and neurochemical parameters in rats fed with a highly palatable diet (HPD) consisted of sucrose (65% carbohydrates being 34% from condensed milk, 8% from sucrose and 23% from starch, 25% protein and 10% fat). Animals were divided into 4 groups: standard chow, standard chow + PcRT extract (200 mg/Kg/day by gavage), HPD, HPD + extract. The animals were treated for 150 days. Concerning chemical profiling, LC/PDA/MS/MS analysis revealed cyanidin-3-O-glucoside as the only anthocyanin in the PcRT extract. Our results showed that the animals exposed to HPD presented glucose intolerance, increased weight gain and visceral fat, as well as higher serum levels of glucose, triacylglycerol, total cholesterol, LDL-cholesterol and interleukin-6. These alterations were prevented by PcRT. In addition, HPD caused an increase in immobility time in a forced swimming test and the fruit extract prevented this alteration, indicating an antidepressant-like effect. PcRT treatment also prevented increased acetylcholinesterase activity in the prefrontal cortex caused by HPD consumption. Moreover, PcRT extract was able to restore Ca2+-ATPase activity in the prefrontal cortex, hippocampus, and striatum, as well as Na+,K+-ATPase activity in the prefrontal cortex and hippocampus. PcRT treatment decreased thiobarbituric acid-reactive substances, nitrite, and reactive oxygen species levels and prevented the reduction of superoxide dismutase activity in all cerebral structures of the HPD group. Additionally, HPD decreased catalase in the hippocampus and striatum. However, the extract prevented this change in the hippocampus. Our results showed that this berry extract has antihyperglycemic and antihyperlipidemic effects, and neuroprotective properties, proving to be a potential therapeutic agent for individuals with metabolic syndrome.


Metabolic syndrome Highly palatable diet P. cattleianum Natural products Phenolic compounds Neuroprotection 



The Brazilian research funding agencies FAPERGS, CAPES and CNPq supported this study. We also thank Dr. Felipe Dal-Pizzol (Laboratory of Experimental Pathophysiology, University of Southern Santa Catarina, Brazil) for providing the kit to measure IL-6.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest in this study.


  1. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126CrossRefPubMedGoogle Scholar
  2. Aksenov MY, Markesbery WR (2001) Changes in thiol content and expression of glutathione redox system genes on the hippocampus and cerebellum in Alzheimer’s disease. Neurosci Lett 302:141–145CrossRefPubMedGoogle Scholar
  3. Ali SF, Lebel CP, Bondy SC (1992) Reactive oxygen species formation as a biomarker of methylmercury and trimethyltin neurotoxicity. Neurotoxicology 13:637–648PubMedGoogle Scholar
  4. Ambrósio G, Kaufmann FN, Manosso L, Platt N, Ghisleni G, Rodrigues ALS, Rieger DK, Kaster MP (2018) Depression and peripheral inflammatory profile of patients with obesity. Psychoneuroendocrinology 91:132–141CrossRefPubMedGoogle Scholar
  5. Auberval N, Dal S, Maillard E, Bietiger W, Peronet C, Pinget M, Schini-Kerth V, Sigrist S (2017) Beneficial effects of a red wine polyphenol extract on high-fat diet-induced metabolic syndrome in rats. Eur J Nutr 56:1467–1475CrossRefPubMedGoogle Scholar
  6. Bagul PK, Middela H, Matapally S, Padya R, Bastia T, Madhusudana K, Reddy RB, Chakravarty S, Banerjee SK (2012) Attenuation of insulin resistance, metabolic syndrome and hepatic oxidative stress by resveratrol in fructose-fed rats. Pharmacol Res 66:260–268CrossRefPubMedGoogle Scholar
  7. Batista KS, Alves AF, Lima MDS, da Silva LA, Lins PP, de Sousa Gomes JA, Silva AS, Toscano LT, de Albuquerque Meireles BRL, de Magalhães Cordeiro AMT, da Conceição ML, de Souza EL, Aquino JS (2018) Beneficial effects of consumption of acerola, cashew or guava processing by-products on intestinal health and lipid metabolism in dyslipidaemic female Wistar rats. Br J Nutr 119:30–41CrossRefPubMedGoogle Scholar
  8. Bhaswant M, Fanning K, Netzel M, Mathai ML, Panchal SK, Brown L (2015) Cyanidin 3-glucoside improves diet-induced metabolic syndrome in rats. Pharmacol Res 102:208–217CrossRefPubMedGoogle Scholar
  9. Biegelmeyer R, Andrade JMM, Aboy AL, Apel MS, Dresch RR, Marin R, Raseira MCB, Henriques AT (2011) Comparative analysis of the chemical composition and antioxidant activity of red (Psidium cattleianum) and yellow (Psidium cattleianum var. lucidum) strawberry guava fruit. J Food Sci 76:991–996CrossRefGoogle Scholar
  10. Bordignon CL, Francescatto V, Nienow AA, Calvete E, Reginatto FH (2009) Influência do pH da solução extrativa no teor de antocianinas em frutos de morango. Ciênc Tecnol Aliment 29:183–188CrossRefGoogle Scholar
  11. Bradford MA (1976) Rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein–dye binding. Anal Biochem 72:248–254CrossRefPubMedGoogle Scholar
  12. Bullo CAP, Migo CP, Aranceta J, Salas SJ (2007) Inflammation, obesity and comorbidities: the role of diet. Public Health Nutr 10:1164–1172CrossRefPubMedGoogle Scholar
  13. Carmona F, Pereira AMS (2013) Herbal medicines: old and new concepts, truths and misunderstandings. Braz J Pharmacog 23:379–385CrossRefGoogle Scholar
  14. Carvalho FB, Gutierres JM, Bohnert C, Zago AM, Abdalla FH, Vieira JM, Palma HE, Oliveira SM, Spanevello RM, Duarte MM, Lopes ST, Aiello GM, Amaral G, Pippi NL Andrade CM (2015) Anthocyanins suppress the secretion of proinflammatory mediators and oxidative stress, and restore ion pump activities in demyelination. J Nutr Biochem 26:378–390CrossRefPubMedGoogle Scholar
  15. Collins B, Hoffman J, Martinez K, Grace M, Lila MA, Cockrell C, Nadimpalli A, Chang E, Chuang CC, Zhong W, Shen W, Cooney P, Hopkins R, Mcintosh M (2016) A polyphenol-rich fraction obtained from table grapes decreases adiposity, insulin resistance, and markers of inflammation and impacts gut microbiota in high-fat fed mice. J Nutr Biochem 31:150–165CrossRefPubMedPubMedCentralGoogle Scholar
  16. Cravotto G, Boffa L, Genzini L, Garella D (2010) Phytotherapeutics: an evaluation of the potential of 1000 plants. J Clin Pharm Ther 35:11–48CrossRefPubMedGoogle Scholar
  17. Da Silva NA, Rodrigues E, Mercadame AZ, Rosso VV (2014) Phenolic compounds and carotenoids from four fruits native from the Brazilian Atlantic Forest. Agric Food Chem 62:5072−5084Google Scholar
  18. Devalaraja S, Jain S, Yadav H (2011) Exotic fruits as therapeutic complements for diabetes, obesity and metabolic syndrome. Food Res Int 44:1856–1865CrossRefPubMedPubMedCentralGoogle Scholar
  19. Ellman GL, Courtney KD, Andres V, Featherstone RMA (1961) New and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7:88–95CrossRefPubMedGoogle Scholar
  20. Erlanson-Albertsson C (2005) How palatable food disrupts appetite regulation. Basic Clin Pharmacol Toxicol 97:61–73CrossRefPubMedGoogle Scholar
  21. Farooqui AA, Farooqui T, Panza F, Frisardi V (2012) Metabolic syndrome as a risk factor for neurological disorders. Cell Mol Life Sci 69:741–762CrossRefPubMedGoogle Scholar
  22. Fiske CH, Subbarow Y (1927) The nature of the “inorganic phosphate” in voluntary muscle. Sci 65:401–403CrossRefGoogle Scholar
  23. Gamaro GD, Streck EL, Matte C, Prediger ME, Wyse AT (2003) Reduction of hippocampal Na+, K+-ATPase activity in rats subjected to an experimental model of depression. Neurochem Res 28:1339–1344CrossRefPubMedGoogle Scholar
  24. Gancheva S, Galunska B, Zhelyazkova-Savova M (2017) Diets rich in saturated fat and fructose induce anxiety and depression-like behaviours in the rat: is there a role for lipid peroxidation? Int J Exp Pathol 98:296–306CrossRefPubMedPubMedCentralGoogle Scholar
  25. Gazal M, Kaufmann FN, Acosta BA, Oliveira PS, Valente MR, Ortmann CF, Sturbelle R, Lencina CL, Stefanello FM, Kaster MP, Reginatto FH, Ghisleni G (2015) Preventive effect of Cecropia pachystachya against ketamine-induced manic behavior and oxidative stress in rats. Neurochem Res 40:1421–1430CrossRefPubMedGoogle Scholar
  26. Guo H, Liu G, Zhong R, Wang Y, Wang D, Xia M (2010) Cyanidin-3-O-b-glucoside regulates fatty acid metabolism via an AMP-activated protein kinase dependent signaling pathway in human HepG2 cells. Int J Mol Sci 11:1365–1402CrossRefGoogle Scholar
  27. Halliwell B, Gutteridge JM (2007) Free Radic biol med. Oxford University Press, New YorkGoogle Scholar
  28. Hanhineva K, Törrönen R, Bondia-Pons I, Pekkinen J, Kolehmainen M, Mykkänen H, Poutanen K (2010) Impact of dietary polyphenols on carbohydrate metabolism. Int J Mol Sci 11:1365–1402CrossRefPubMedPubMedCentralGoogle Scholar
  29. Huang W, Lin Y, Wang Tsai C, Tseng H, Chen C, Lu P, Chen P, Qian L, Hong J, Lin C (2009) Glycogen synthase kinase-3 negatively regulates anti-inflammatory interleukin-10 for lipopolysaccharide-induced iNOS/NO biosynthesis and RANTES production in microglial cells. Immunol 128:275–286CrossRefGoogle Scholar
  30. Huynh TN, Krigbaum AM, Hanna JJ, Conrad CD (2011) Sex differences and phase of light cycle modify chronic stress effects on anxiety and depressive-like behavior. Behav Brain Res 222:212–222CrossRefPubMedGoogle Scholar
  31. Inhwan IM, Kyung-Ran P, Sung-Moo K, Chulwon K, Jeong HAP, Dongwoo N, Hyeung-Jin J, Bum Sang S, Kyoo Seok A (2012) The butanol fraction of guava (Psidium cattleianum Sabine) leaf extract suppresses MMP-2 and MMP-9 expression and activity through the suppression of the ERK1/2 MAPK signaling pathway. Nutr Cancer 64:255–266CrossRefGoogle Scholar
  32. Jayarathne S, Koboziev I, Park O, Oldewage-Theron W, Shen C, Moustaid-Moussa N (2017) Anti-inflammatory and anti-obesity properties of food bioactive components: effects on adipose tissue. Prev Nutr Food Sci 22:251–262CrossRefPubMedPubMedCentralGoogle Scholar
  33. Kade IJ, Rocha JBT (2013) Gallic acid modulates cerebral oxidative stress conditions and activities of enzyme-dependent signaling systems in Streptozotocin-treated rats. Neurochem Res 38:761–771CrossRefPubMedGoogle Scholar
  34. Khanal RC, Howard LR, Wilkes SE, Rogers TJ, Ronald L, Prior RL (2012) Effect of dietary blueberry pomace on selected metabolic factors associated with high fructose feeding in growing Sprague–Dawley rats. J Med Food 15:802–810CrossRefPubMedGoogle Scholar
  35. Kirshenbaum GS, Saltzman K, Rose B, Petersen J, Vilsen B, Roder JC (2011) Decreased neuronal Na+, K+ -ATPase activity in Atp1a3 heterozygous mice increases susceptibility to depression-like endophenotypes by chronic variable stress. Genes Brain Behav 10:542–550CrossRefPubMedGoogle Scholar
  36. Kumar B, Arora V, Kuhad A, Chopra K (2012) Vaccinium myrtillus ameliorates unpredictable chronic mild stress induced depression: possible involvement of nitric oxide pathway. Phytother Res 26:488–497CrossRefPubMedGoogle Scholar
  37. Lee J, Durst RW, Wrolstad RE (2005) Determination of total monomeric anthocyanin pigment content of fruit juices, beverages, natural colorants and wines by the pH differential method: collaborative study. J AOAC Int 8:1269–1278Google Scholar
  38. Liapi C, Kyriakaki A, Zarros A, Galanopoulou P, Al-Humadi H, Dontas I, Voumvourakis K, Tsakiris T (2010) Choline-deprivation alters crucial brain enzyme activities in a rat model of diabetic encephalopathy. Metab Brain Dis 25:269–276CrossRefPubMedGoogle Scholar
  39. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  40. Madani Z, Malaisse WJ, Ait-Yahia D (2015) A comparison between the impact of two types of dietary protein on brain glucose concentrations and oxidative stress in high fructose-induced metabolic syndrome rats. Biomed Reports 3:731–735CrossRefGoogle Scholar
  41. Manzano S, Williamson G (2010) Polyphenols and phenolic acids from strawberry and apple decrease glucose uptake and transport by human intestinal Caco-2 cells. Mol Nutr Food Res 54:1773–1780CrossRefPubMedGoogle Scholar
  42. Mattos Jr. (1989) Myrtaceae do Rio Grande do Sul. Porto Alegre: CEUE. pp.721Google Scholar
  43. Melo JB, Agostinho P, Oliveira CR (2003) Involvement of oxidative stress in the enhancement of acetylcholinesterase activity induced by amyloid beta-peptide. Neurosci Res 45:17–127CrossRefGoogle Scholar
  44. Miliauskas G, Venskutonis PR, Van TA (2004) Screening of radical scavenging activity of some medicinal and aromatic plant extracts. Food Chem 85:231–237CrossRefGoogle Scholar
  45. Misra HP, Fridovich I (1972) The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem 247:3170–3175PubMedGoogle Scholar
  46. Nishi A, Fisone G, Snyder GL, Dulubova I, Aperia A, Nairn AC, Greengard P (1999) Regulation of Na+, K+-ATPase isoforms in rat neostriatum by dopamine and protein kinase C. J Neurochem 73:1492–1501CrossRefPubMedGoogle Scholar
  47. Ohkawa H, Ohishi Ν, Yagi Κ (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358CrossRefPubMedGoogle Scholar
  48. Oliveira PS, Gazal M, Flores NP, Zimmer AR, Chaves VC, Reginatto FH, Kaster MP, Tavares RG, Spanevello RM, Lencina CL, Stefanello FM (2017a) Vaccinium virgatum fruit extract as an important adjuvant in biochemical and behavioral alterations observed in animal model of metabolic syndrome. Biomed Pharmacother 88:939–947CrossRefPubMedGoogle Scholar
  49. Oliveira PS, Chaves VC, Bona NP, Soares MSP, Cardozo JS, Vasconcellos FA, Tavares RG, Vizzotto M, Da Silva LMC, Grecco FB, Gamaro GD, Spanevello RM, Lencina CL, Reginatto FH, Stefanello FM (2017b) Eugenia uniflora fruit (red type) standardized extract: a potential pharmacological tool to diet-induced metabolic syndrome damage management. Biomed Pharmacother 92:935–941CrossRefPubMedGoogle Scholar
  50. Paredes-Lopez O, Cervantes-Ceja ML, Vigna-Perez M, Hernandez-Perez T (2010) Berries: improving human health and healthy aging, and promoting quality life. Plant Foods Hum Nutr 65:299–308CrossRefPubMedGoogle Scholar
  51. Quines CB, Rosa SG, Velasquez D, Da Rocha JT, Neto JSS, Nogueira CW (2016) Diphenyldiselenide elicits antidepressant-like activity in rats exposed to monosodium glutamate: a contribution of serotonin uptake and Na+,K+-ATPase activity. Behav Brain Res 301:161–167CrossRefPubMedGoogle Scholar
  52. Rambo LM, Ribeiro LR, Schramm VG, Berch AM, Stamm DN, Della-Pace ID, Silva LF, Furian AF, Oliveira MS, Fighera MR, Royes LF (2012) Creatine increases hippocampal Na(+),K(+)-ATPase activity via NMDA-calcineurin pathway. Brain Res Bull 88:553–559CrossRefPubMedGoogle Scholar
  53. Raskin I, Ripoll C (2004) Can an apple a day keep the doctor away? Curr Pharm Des 10:3419–3429CrossRefPubMedGoogle Scholar
  54. Ribeiro AB, Chisté RC, Freitas M, Da Silva AF, Visentainer JV, Fernandes E (2014) Psidium cattleianum fruit extracts are efficient in vitro scavengers of physiologically relevant reactive oxygen and nitrogen species. Food Chem 165:140–148CrossRefPubMedGoogle Scholar
  55. Rudolf S, Greggersen W, Kahl KG, Huppe US (2014) Elevated IL-6 levels in patients with atypical depression but not in patients with typical depression. Psychiatry Res 217:34–38CrossRefPubMedGoogle Scholar
  56. Shah A, Mehta N, Reilly MP (2008) Adipose inflammation, insulin resistance, and cardiovascular disease. J Parenter Enter Nutr 32:638–644CrossRefGoogle Scholar
  57. Sharma D, Setthi P, Hussain E, Singh R (2009) Curcumin counteracts the aluminium-induced ageing-related alterations in oxidative stress, Na+, K+ ATPase and protein kinase C in adult and old rat brain regions. Biogerontology 10:489–502CrossRefPubMedGoogle Scholar
  58. Silva L, Figueiredo E, Ricardo N, Vieira L, Figueiredo R, Brasil L, Gomes C (2014) Quantification of bioactive compounds in pulps and by-products of tropical fruits from Brazil. Food Chem 143:398–404CrossRefGoogle Scholar
  59. Singleton VL, Orthefer R, Lamuela-Ranventós, R (1999). Analysis of total phenols and other oxidation substrates and antioxidants by means of Folin-Ciocalteau reagent. In: Methods Enzymol, (Parker L, ed.) (pp. 152–159). Academic Press, Section IIIGoogle Scholar
  60. Srikanthan K, Shapiro JI, Sodhi K (2016) The role of Na/K-ATPase signaling in oxidative stress related to obesity and cardiovascular disease. Molecules 21:1–13CrossRefGoogle Scholar
  61. Tey SL, Lee DEM, Henry CJ (2017) Fruit form influences postprandial glycemic response in elderly and young adults. J Nutr Health Aging 21:887–891CrossRefPubMedGoogle Scholar
  62. Treviño S, Aguilar-Alonso P, Flores Hernandez JA, Brambila E, Guevara J, Flores G, Lopez-Lopez G, Muñoz-Arenas G, Morales-Medina JC, Toxqui V, Venegas B, Diaz A (2015) A high calorie diet causes memory loss, metabolic syndrome and oxidative stress into hippocampus and temporal cortex of rats. Synapse 69:421–433CrossRefPubMedGoogle Scholar
  63. Vendrame S, Del Bo’ C, Ciappellano S, Riso P, Klimis-Zacas D (2016) Berry fruit consumption and metabolic syndrome. Antioxidants 5:1–21CrossRefGoogle Scholar
  64. Wellen KE, Thompson CB (2010) Cellular metabolic stress: considering how cells respond to nutrient excess. Mol Cell 40:323–332CrossRefPubMedPubMedCentralGoogle Scholar
  65. Williamson EM (2001) Synergy and other interaction in phytomedicines. Phytomedicine 8:401–409CrossRefPubMedGoogle Scholar
  66. Zarros A, Liapi C, Galanopoulou P, Marinou K, Mellios Z, Skandali N, Al-humadi H, Anifantaki F, Gkrouzman E, Tsakiris S (2009) Effects of adult-onset streptozotocin-induced diabetes on the rat brain antioxidant status and the activities of acetylcholinesterase, (Na+,K+)- and Mg2+-ATPase: modulation by L-cysteine. Metab Brain Dis 24:337–348CrossRefPubMedGoogle Scholar
  67. Zhang XY, Yao JK (2013) Oxidative stress and therapeutic implications in psychiatric disorders. Prog Neuropsychopharmacol Biol 46:197–199CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Pathise Souto Oliveira
    • 1
  • Vitor Clasen Chaves
    • 2
  • Mayara Sandrielly Pereira Soares
    • 3
  • Natália Pontes Bona
    • 1
  • Lorenço Torres Mendonça
    • 1
  • Fabiano Barbosa Carvalho
    • 4
  • Jessié Martins Gutierres
    • 4
  • Flávia Aleixo Vasconcellos
    • 5
  • Marcia Vizzotto
    • 6
  • Andriele Vieira
    • 7
  • Roselia Maria Spanevello
    • 3
  • Flávio Henrique Reginatto
    • 2
  • Claiton Leoneti Lencina
    • 1
  • Francieli Moro Stefanello
    • 1
    • 8
    Email author
  1. 1.Laboratório de Biomarcadores, Centro de Ciências Químicas, Farmacêuticas e de AlimentosUniversidade Federal de PelotasPelotasBrazil
  2. 2.Laboratório de Farmacognosia, Programa de Pós-Graduação em Biotecnologia e BiociênciasUniversidade Federal de Santa CatarinaFlorianópolisBrazil
  3. 3.Laboratório de Neuroquímica, Inflamação e Câncer, Centro de Ciências Químicas, Farmacêuticas e de AlimentosUniversidade Federal de PelotasPelotasBrazil
  4. 4.Programa de Pós-Graduação em Ciências Biológicas: Bioquímica Toxicológica, Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e ExatasUniversidade Federal de Santa MariaSanta MariaBrazil
  5. 5.Laboratório de Química Aplicada a Bioativos, Centro de Ciências Químicas, Farmacêuticas e de AlimentosUniversidade Federal de PelotasPelotasBrazil
  6. 6.Empresa Brasileira de Pesquisa Agropecuária, Centro de Pesquisa Agropecuária de Clima TemperadoPelotasBrazil
  7. 7.Laboratório de Fisiopatologia, Programa de Pós-Graduação em Ciências da SaúdeUniversidade do Extremo Sul CatarinenseCriciúmaBrazil
  8. 8.Universidade Federal de PelotasCapão do LeãoBrazil

Personalised recommendations