Neurochemical Research

, Volume 37, Issue 9, pp 1928–1937 | Cite as

Neuroprotective Effects of Bacopa monnieri in Experimental Model of Dementia

  • Neetu Saini
  • Devinder Singh
  • Rajat SandhirEmail author
Original Paper


Alzheimer disease (AD) is characterized by dementia that begins as mild short term memory deficit and culminates in total loss of cognitive and executive functions. The present study was conducted to evaluate the neuroprotective potential of Bacopa monnieri (BM), an Indian traditional medicinal plant effective against cognitive impairment, in colchicine-induced dementia. Intracerebroventricular administration of colchicine (15 μg/5 μl) induced cognitive impairment in rats as assessed by elevated plus maze. This was accompanied by a significant increase in oxidative stress in term of enhanced levels of lipid peroxidation and protein carbonyls. Concomitantly, decrease in activity of antioxidant enzymes was observed in colchicine treated animals. BM (50 mg/kg body weight) supplementation reversed memory impairment observed in the colchicine treated rats. BM administration attenuated oxidative damage, as evident by decreased LPO and protein carbonyl levels and restoration in activities of the antioxidant enzymes. The activity of membrane bound enzymes (Na+K+ ATPase and AChE) was altered in colchicine treated brain regions and BM supplementation was able to restore the activity of enzymes to comparable values observed in controls. The results suggest therapeutic potential of BM in the treatment of AD associated cognitive decline.


Alzheimer’s disease Antioxidants Bacopa monnieri Colchicine Dementia Oxidative stress 



The financial assistance provided from Department of Science and Technology (DST) New Delhi, under women scientist fellowship and DST-PURSE grants is highly acknowledged.

Conflict of interest

The authors have no conflicts of interest to disclose.


  1. 1.
    Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM (2007) Forecasting the global burden of Alzheimer’s disease. Alzheimers Dement 3:186–191PubMedCrossRefGoogle Scholar
  2. 2.
    Armstrong RA (2006) Measuring the spatial arrangement patterns of pathological lesions in histological sections of brain tissue. Folia Neuropathol 44:229–237PubMedGoogle Scholar
  3. 3.
    Portelius E, Zetterberg H, Andreasson U, Brinkmalm G, Andreasen N, Wallin A, Westman-Brinkmalm A, Blennow K (2006) An Alzheimer’s disease-specific beta-amyloid fragment signature in cerebrospinal fluid. Neurosci Lett 409:215–219PubMedCrossRefGoogle Scholar
  4. 4.
    Bartus RT (2000) On neurodegenerative diseases, models, and treatment strategies: lessons learned and lessons forgotten a generation following the cholinergic hypothesis. Exp Neurol 163:495–529PubMedCrossRefGoogle Scholar
  5. 5.
    Schliebs R, Arendt T (2006) The significance of the cholinergic system in the brain during aging and in Alzheimer’s disease. J Neural Transm 113:1625–1644PubMedCrossRefGoogle Scholar
  6. 6.
    Windelborn JA, Lipton P (2008) Lysosomal release of cathepsins causes ischemic damage in the rat hippocampal slice and depends on NMDA-mediated calcium influx, arachidonic acid metabolism, and free radical production. J Neurochem 106:56–69PubMedCrossRefGoogle Scholar
  7. 7.
    Reddy PH (2007) Mitochondrial dysfunction in aging and Alzheimer’s disease: strategies to protect neurons. Antioxid Redox Signal 9:1647–1658PubMedCrossRefGoogle Scholar
  8. 8.
    Ishrat T, Parveen K, Hoda MN, Khan MB, Yousuf S, Ansari MA, Saleem S, Islam F (2009) Effects of Pycnogenol and vitamin E on cognitive deficits and oxidative damage induced by intracerebroventricular streptozotocin in rats. Behav Pharmacol 20:567–575PubMedCrossRefGoogle Scholar
  9. 9.
    Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84PubMedCrossRefGoogle Scholar
  10. 10.
    Nakayama T, Sawada T (2002) Involvement of microtubule integrity in memory impairment caused by colchicine. Pharmacol Biochem Behav 71:119–138PubMedCrossRefGoogle Scholar
  11. 11.
    Muller GJ, Geist MA, Veng LM, Willesen MG, Johansen FF, Leist M, Vaudano E (2006) A role for mixed lineage kinases in granule cell apoptosis induced by cytoskeletal disruption. J Neurochem 96:1242–1252PubMedCrossRefGoogle Scholar
  12. 12.
    Goldschmidt RB, Steward O (1982) Neurotoxic effects of colchicine: differential susceptibility of CNS neuronal populations. Neuroscience 7:695–714PubMedCrossRefGoogle Scholar
  13. 13.
    Kumar V, Gupta YK (2002) Intracerebroventricular administration of colchicine produces cognitive impairment associated with oxidative stress in rats. Pharmacol Biochem Behav 73:565–571CrossRefGoogle Scholar
  14. 14.
    Bensimon G, Chermat R (1991) Microtubule disruption and cognitive defects: effect of colchicine on learning behavior in rats. Pharmacol Biochem Behav 38:141–145PubMedCrossRefGoogle Scholar
  15. 15.
    Nakagawa Y, Nakamura S, Kase Y, Noguchi T, Ishihara T (1987) Colchicine lesions in the rat hippocampus mimic the alterations of several markers in Alzheimer’s disease. Brain Res 408:57–64PubMedCrossRefGoogle Scholar
  16. 16.
    Blazer DG, Federspiel CF, Ray WA, Schaffner W (1983) The risk of anticholinergic toxicity in the elderly: a study of prescribing practices in two populations. J Gerontol 38:31–35PubMedGoogle Scholar
  17. 17.
    Rogers SL, Farlow MR, Doody RS, Mohs R, Friedhoff LT (1998) A 24 week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer’s disease (Donepezil Study Group). Neurology 50:136–145PubMedCrossRefGoogle Scholar
  18. 18.
    Howes MJ, Houghton PJ (2012) Ethnobotanical treatment strategies against Alzheimer’s disease. Curr Alzheimer Res 9:67–85PubMedCrossRefGoogle Scholar
  19. 19.
    Anekonda TS, Reddy PH (2005) Can herbs provide a new generation of drugs for treating Alzheimer’s disease? Brain Res Brain Res Rev 50:361–376PubMedCrossRefGoogle Scholar
  20. 20.
    Dos Santos-Neto LL, de Vilhena Toledo MA, Medeiros-Souza P, de Souza GA (2006) The use of herbal medicine in Alzheimer’s disease-a systematic review. Evid Based Complement Alternat Med 3:441–445PubMedCrossRefGoogle Scholar
  21. 21.
    Ono K, Hasegawa K, Naiki H, Yamada M (2004) Curcumin has potent anti-amyloidogenic effects for Alzheimer’s beta-amyloid fibrils in vitro. J Neurosci Res 75:742–750PubMedCrossRefGoogle Scholar
  22. 22.
    Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP, Kayed R, Glabe CG, Frautschy SA, Cole GM (2005) Curcumin inhibits formation of amyloid beta oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J Biol Chem 280:5892–5901PubMedCrossRefGoogle Scholar
  23. 23.
    Stackman RW, Eckenstein F, Frei B, Kulhanek D, Nowlin J, Quinn JF (2003) Prevention of age-related spatial memory deficits in a transgenic mouse model of Alzheimer’s disease by chronic Ginkgo biloba treatment. Exp Neurol 184:510–520PubMedCrossRefGoogle Scholar
  24. 24.
    Garai S, Mahato SB, Ohtani K, Yamasaki K (1996) Bacopasaponin D—a pseudojujubogenin glycoside from Bacopa monniera. Phytochemistry 43:447–449PubMedCrossRefGoogle Scholar
  25. 25.
    Shinomol GK, Bharath MM, Muralidhara (2011) Neuromodulatory propensity of Bacopa monnieri leaf extract against 3-nitropropionic acid-induced oxidative stress: in vitro and in vivo evidences. Neurotox Res 22:102–114Google Scholar
  26. 26.
    Bhattacharya SK, Bhattacharya A, Kumar A, Ghosal S (2000) Antioxidant activity of Bacopa monniera in rat frontal cortex, striatum and hippocampus. Phytother Res 14:174–179PubMedCrossRefGoogle Scholar
  27. 27.
    Deepak M, Sangli GK, Arun PC, Amit A (2005) Quantitative determination of the major saponin mixture bacoside A in Bacopa monnieri by HPLC. Phytochem Anal 16:24–29PubMedCrossRefGoogle Scholar
  28. 28.
    Mishra S, Srivastava S, Dwivedi S, Tripathi RD (2011) Investigation of biochemical responses of Bacopa monnieri L. upon exposure to arsenate. Environ Toxicol. doi: 10.1002/tox.20733
  29. 29.
    Zhou Y, Peng L, Zhang WD, Kong DY (2009) Effect of triterpenoid saponins from Bacopa monniera on scopolamine-induced memory impairment in mice. Planta Med 75:568–574PubMedCrossRefGoogle Scholar
  30. 30.
    Holcomb LA, Dhanasekaran M, Hitt AR, Young KA, Riggs M, Manyam BV (2006) Bacopa monniera extract reduces amyloid levels in PSAPP mice. J Alzheimers Dis 9:243–251PubMedGoogle Scholar
  31. 31.
    Limpeanchob N, Jaipan S, Rattanakaruna S, Phrompittayarat W, Ingkaninan K (2008) Neuroprotective effect of Bacopa monnieri on beta-amyloid-induced cell death in primary cortical culture. J Ethnopharmacol 120:112–117PubMedCrossRefGoogle Scholar
  32. 32.
    Uabundit N, Wattanathorn J, Mucimapura S, Ingkaninan K (2010) Cognitive enhancement and neuroprotective effects of Bacopa monnieri in Alzheimer’s disease model. J Ethnopharmacol 127:26–31PubMedCrossRefGoogle Scholar
  33. 33.
    Calabrese C, Gregory WL, Leo M, Kraemer D, Bone K, Oken B (2008) Effects of a standardized Bacopa monnieri extract on cognitive performance, anxiety, and depression in the elderly: a randomized, double-blind, placebo-controlled trial. J Altern Complement Med 14:707–713PubMedCrossRefGoogle Scholar
  34. 34.
    Roodenrys S, Booth D, Bulzomi S, Phipps A, Micallef C, Smoker J (2002) Chronic effects of Brahmi (Bacopa monnieri) on human memory. Neuropsychopharmacology 27:279–281PubMedCrossRefGoogle Scholar
  35. 35.
    Kumar A, Dogra S, Prakash A (2009) Neuroprotective effects of Centella asiatica against intracerebroventricular colchicine-induced cognitive impairment and oxidative stress. Int J Alzheimers Dis 2009:pii972178Google Scholar
  36. 36.
    Jyoti A, Sethi P, Sharma D (2007) Bacopa monniera prevents from aluminium neurotoxicity in the cerebral cortex of rat brain. J Ethnopharmacol 111:56–62PubMedCrossRefGoogle Scholar
  37. 37.
    Khurana S, Jain S, Mediratta PK, Banerjee BD, Sharma KK (2012) Protective role of curcumin on colchicine-induced cognitive dysfunction and oxidative stress in rats. Hum Exp Toxicol. doi: 10.1177/0960327111433897
  38. 38.
    Paxinos G, Watson C, Pennisi M, Topple A (1985) Bregma, lambda and the interaural midpoint in stereotaxic surgery with rats of different sex, strain and weight. J Neurosci Methods 13:139–143PubMedCrossRefGoogle Scholar
  39. 39.
    Itoh J, Nabeshima T, Kameyama T (1991) Utility of an elevated plus-maze for dissociation of amnesic and behavioral effects of drugs in mice. Eur J Pharmacol 194:71–76PubMedCrossRefGoogle Scholar
  40. 40.
    Cartmell SM, Gelgor L, Mitchell D (1991) A revised rotarod procedure for measuring the effect of antinociceptive drugs on motor function in the rat. J Pharmacol Methods 26:149–159PubMedCrossRefGoogle Scholar
  41. 41.
    Gray EG, Whittaker VP (1962) The isolation of nerve endings from brain: an electron-microscopic study of cell fragments derived by homogenization and centrifugation. J Anat 96:79–88PubMedGoogle Scholar
  42. 42.
    Meder W, Fink K, Gothert M (1997) Involvement of different calcium channels in K+- and veratridine-induced increases of cytosolic calcium concentration in rat cerebral cortical synaptosomes. Naunyn Schmiedebergs Arch Pharmacol 356:797–805PubMedCrossRefGoogle Scholar
  43. 43.
    Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358PubMedCrossRefGoogle Scholar
  44. 44.
    Levine RL, Garland D, Oliver CN, Amici A, Climent I, Lenz AG, Ahn BW, Shaltiel S, Stadtman ER (1990) Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 186:464–478PubMedCrossRefGoogle Scholar
  45. 45.
    Roberts JC, Francetic DJ (1993) The importance of sample preparation and storage in glutathione analysis. Anal Biochem 211:183–187PubMedCrossRefGoogle Scholar
  46. 46.
    Kono Y (1978) Generation of superoxide radical during autoxidation of hydroxylamine and an assay for superoxide dismutase. Arch Biochem Biophys 186:189–195PubMedCrossRefGoogle Scholar
  47. 47.
    Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126PubMedCrossRefGoogle Scholar
  48. 48.
    Flohe L, Gunzler WA (1984) Assays of glutathione peroxidase. Methods Enzymol 105:114–121PubMedCrossRefGoogle Scholar
  49. 49.
    Carlberg I, Mannervik B (1985) Glutathione reductase. Methods Enzymol 113:484–490PubMedCrossRefGoogle Scholar
  50. 50.
    Warholm M, Guthenberg C, von Bahr C, Mannervik B (1985) Glutathione transferases from human liver. Methods Enzymol 113:499–504PubMedCrossRefGoogle Scholar
  51. 51.
    Whittaker MW (1984) Cholinesterases. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Verlag Chemie, Weinheim, pp 52–74Google Scholar
  52. 52.
    Quigley JP, Gotterer GS (1969) Distribution of (Na+-K+)-stimulated ATPase activity in rat intestinal mucosa. Biochim Biophys Acta 173:456–468PubMedCrossRefGoogle Scholar
  53. 53.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275PubMedGoogle Scholar
  54. 54.
    Shigematsu K, McGeer PL (1992) Accumulation of amyloid precursor protein in damaged neuronal processes and microglia following intracerebral administration of aluminum salts. Brain Res 593:117–123PubMedCrossRefGoogle Scholar
  55. 55.
    Dringen R, Gutterer JM, Hirrlinger J (2000) Glutathione metabolism in brain metabolic interaction between astrocytes and neurons in the defense against reactive oxygen species. Eur J Biochem 267:4912–4916PubMedCrossRefGoogle Scholar
  56. 56.
    Chatterjee M, Verma P, Palit G (2010) Comparative evaluation of Bacopa monniera and Panax quniquefolium in experimental anxiety and depressive models in mice. Indian J Exp Biol 48:306–313PubMedGoogle Scholar
  57. 57.
    Shinomol GK, Muralidhara (2011) Bacopa monnieri modulates endogenous cytoplasmic and mitochondrial oxidative markers in prepubertal mice brain. Phytomedicine 18: 317–326Google Scholar
  58. 58.
    Kapoor R, Srivastava S, Kakkar P (2009) Bacopa monnieri modulates antioxidant responses in brain and kidney of diabetic rats. Environ Toxicol Pharmacol 27:62–69PubMedCrossRefGoogle Scholar
  59. 59.
    Dhanasekaran M, Tharakan B, Holcomb LA, Hitt AR, Young KA, Manyam BV (2007) Neuroprotective mechanisms of ayurvedic antidementia botanical Bacopa monniera. Phytother Res 21:965–969PubMedCrossRefGoogle Scholar
  60. 60.
    Bharath S, Hsu M, Kaur D, Rajagopalan S, Andersen JK (2002) Glutathione, iron and Parkinson’s disease. Biochem Pharmacol 64:1037–1048PubMedCrossRefGoogle Scholar
  61. 61.
    Jyoti A, Sharma D (2006) Neuroprotective role of Bacopa monniera extract against aluminium-induced oxidative stress in the hippocampus of rat brain. Neurotoxicology 27:451–457PubMedCrossRefGoogle Scholar
  62. 62.
    Liochev SI, Fridovich I (2003) Mutant Cu, Zn superoxide dismutases and familial amyotrophic lateral sclerosis: evaluation of oxidative hypotheses. Free Radic Biol Med 34:1383–1389PubMedCrossRefGoogle Scholar
  63. 63.
    Zelko IN, Mariani TJ, Folz RJ (2002) Superoxide dismutase multigene family: a comparison of the CuZn-SOD (SOD1), Mn-SOD (SOD2), and EC-SOD (SOD3) gene structures, evolution, and expression. Free Radic Biol Med 33:337–349PubMedCrossRefGoogle Scholar
  64. 64.
    Chelikani P, Fita I, Loewen PC (2004) Diversity of structures and properties among catalases. Cell Mol Life Sci 61:192–208PubMedCrossRefGoogle Scholar
  65. 65.
    Russo A, Borrelli F (2005) Bacopa monniera, a reputed nootropic plant: an overview. Phytomedicine 12:305–317PubMedCrossRefGoogle Scholar
  66. 66.
    Shen KK, Ji LL, Chen Y, Yu QM, Wang ZT (2011) Influence of glutathione levels and activity of glutathione-related enzymes in the brains of tumor-bearing mice. Biosci Trends 5:30–37PubMedCrossRefGoogle Scholar
  67. 67.
    Arthur JR (2000) The glutathione peroxidases. Cell Mol Life Sci 57:1825–1835PubMedCrossRefGoogle Scholar
  68. 68.
    Ishrat T, Parveen K, Khan MM, Khuwaja G, Khan MB, Yousuf S, Ahmad A, Shrivastav P, Islam F (2009) Selenium prevents cognitive decline and oxidative damage in rat model of streptozotocin-induced experimental dementia of Alzheimer’s type. Brain Res 1281:117–127PubMedCrossRefGoogle Scholar
  69. 69.
    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 374:222–226PubMedCrossRefGoogle Scholar
  70. 70.
    Struzynska L, Sulkowski G, Lenkiewicz A, Rafalowska U (2002) Lead stimulates the glutathione system in selective regions of rat brain. Folia Neuropathol 40:203–209PubMedGoogle Scholar
  71. 71.
    Meister A (1988) Glutathione metabolism and its selective modification. J Biol Chem 263:17205–17208PubMedGoogle Scholar
  72. 72.
    Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139PubMedGoogle Scholar
  73. 73.
    Kamboj A, Kiran R, Sandhir R (2006) Carbofuran-induced neurochemical and neurobehavioral alterations in rats: attenuation by N-acetylcysteine. Exp Brain Res 170:567–575PubMedCrossRefGoogle Scholar
  74. 74.
    Milatovic D, Gupta RC, Aschner M (2006) Anticholinesterase toxicity and oxidative stress. ScientificWorldJournal 6:295–310PubMedCrossRefGoogle Scholar
  75. 75.
    Kaur B, Singh N, Jaggi AS (2009) Exploring mechanism of pioglitazone-induced memory restorative effect in experimental dementia. Fundam Clin Pharmacol 23:557–566PubMedCrossRefGoogle Scholar
  76. 76.
    Sharma B, Singh N, Singh M (2008) Modulation of celecoxib- and streptozotocin-induced experimental dementia of Alzheimer’s disease by pitavastatin and donepezil. J Psychopharmacol 22:162–171PubMedCrossRefGoogle Scholar
  77. 77.
    Koladiya RU, Jaggi AS, Singh N, Sharma BK (2008) Ameliorative role of Atorvastatin and Pitavastatin in l-Methionine induced vascular dementia in rats. BMC Pharmacol 8:14PubMedCrossRefGoogle Scholar
  78. 78.
    Barbosa J Jr, Ferreira LT, Martins-Silva C, Santos MS, Torres GE, Caron MG, Gomez MV, Ferguson SS, Prado MA, Prado VF (2002) Trafficking of the vesicular acetylcholine transporter in SN56 cells: a dynamin-sensitive step and interaction with the AP-2 adaptor complex. J Neurochem 82:1221–1228PubMedCrossRefGoogle Scholar
  79. 79.
    Mathew J, Paul J, Nandhu MS, Paulose CS (2010) Increased excitability and metabolism in pilocarpine induced epileptic rats: effect of Bacopa monnieri. Fitoterapia 81:546–551PubMedCrossRefGoogle Scholar
  80. 80.
    Lees AJ (1993) Dopamine agonists in Parkinson’s disease: a look at apomorphine. Fundam Clin Pharmacol 7:121–128PubMedCrossRefGoogle Scholar
  81. 81.
    Kaur J, Sharma D, Singh R (2001) Acetyl-L-carnitine enhances Na+, K+-ATPase glutathione-S-transferase and multiple unit activity and reduces lipid peroxidation and lipofuscin concentration in aged rat brain regions. Neurosci Lett 301:1–4PubMedCrossRefGoogle Scholar
  82. 82.
    Arivazhagan P, Panneerselvam C (2004) Alpha-lipoic acid increases Na+K+ATPase activity and reduces lipofuscin accumulation in discrete brain regions of aged rats. Ann NY Acad Sci 1019:350–354PubMedCrossRefGoogle Scholar
  83. 83.
    Rauchova H, Ledvinkova J, Kalous M, Drahota Z (1995) The effect of lipid peroxidation on the activity of various membrane-bound ATPases in rat kidney. Int J Biochem Cell Biol 27:251–255PubMedCrossRefGoogle Scholar
  84. 84.
    Dobrota D, Matejovicova M, Kurella EG, Boldyrev AA (1999) Na/K-ATPase under oxidative stress: molecular mechanisms of injury. Cell Mol Neurobiol 19:141–149PubMedCrossRefGoogle Scholar
  85. 85.
    Hebbel RP, Shalev O, Foker W, Rank BH (1986) Inhibition of erythrocyte Ca2+-ATPase by activated oxygen through thiol- and lipid-dependent mechanisms. Biochim Biophys Acta 862:8–16PubMedCrossRefGoogle Scholar
  86. 86.
    Cohadon F, Rigoulet M, Guerin B, Vandendriessche M (1979) Vasogenic cerebral oedema. Changes in membrane ATPases. Correction by a phospholipid precursor (author’s transl). Nouv Presse Med 8:1589–1591PubMedGoogle Scholar
  87. 87.
    Shinomol GK, Bharath MM, Muralidhara (2012) Pretreatment with Bacopa monnieri extract offsets 3-nitropropionic acid induced mitochondrial oxidative stress and dysfunctions in the striatum of prepubertal mouse brain. Can J Physiol Pharmacol 90:595–606Google Scholar
  88. 88.
    Sairam K, Rao CV, Babu MD, Goel RK (2001) Prophylactic and curative effects of Bacopa monniera in gastric ulcer models. Phytomedicine 8:423–430PubMedCrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Department of BiochemistryPanjab UniversityChandigarhIndia
  2. 2.Department of ZoologyPunjabi UniversityPatialaIndia

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