Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Amalaki Rasayana improved memory and neuronal metabolic activity in AβPP-PS1 mouse model of Alzheimer’s disease

Abstract

Alzheimer’s disease (AD) is the most common neurodegenerative disorder characterized by progressive loss of memory and cognitive function. The cerebral metabolic rate of glucose oxidation has been shown to be reduced in AD. The present study evaluated efficacy of dietary Amalaki Rasayana (AR), an Ayurvedic formulation used in Indian traditional system, in AβPP-PS1 mouse model of AD in ameliorating memory and neurometabolism, and compared with donepezil, a standard FDA approved drug for AD. The memory of mice was measured using Morris Water Maze analysis. The cerebral metabolism was followed by 13C labelling of brain amino acids in tissue extracts ex vivo using 1H-[13C]-NMR spectroscopy together with a short time infusion of [1,6-13C2]glucose to mice. The intervention with Amalaki Rasayana showed improved learning and memory in AβPP-PS1 mice. The 13C labelings of GluC4, GABAC2 and GlnC4 were reduced in AβPP-PS1 mice when compared with wild-type controls. Intervention of AR increased the 13C labelling of amino acids suggesting a significant enhancement in glutamatergic and GABAergic metabolic activity in AβPP-PS1 mice similar to that observed with donepezil treatment. These data suggest that AR has potential to improve memory and cognitive function in AD.

This is a preview of subscription content, log in to check access.

Figure 1
Figure 2
Figure 3

References

  1. Birks J and Harvey RJ 2006 Donepezil for dementia due to Alzheimer’s disease. Cochrane Database Syst. Rev. CD001190

  2. Braak H and Braak E 1996 Evolution of the neuropathology of Alzheimer’s disease. Acta Neurol. Scand. Suppl. 165 3–12

  3. Butterfield DA, Howard BJ and LaFontaine MA 2001 Brain oxidative stress in animal models of accelerated aging and the age-related neurodegenerative disorders, Alzheimer’s disease and Huntington’s disease. Curr. Med. Chem. 8 815–828

  4. Carlsen MH, Halvorsen BL, Holte K, Bohn SK, Dragland S, Sampson L, Willey C, Senoo H, Umezono Y, Sanada C, Barikmo I, Berhe N, Willett WC, Phillips KM, Jacobs DR, Jr. and Blomhoff R 2010 The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide. Nutr. J. 9 3

  5. de Graaf RA, Mason GF, Patel AB, Behar KL and Rothman DL 2003 In vivo 1H-[13C]-NMR spectroscopy of cerebral metabolism. NMR Biomed. 16 339–357

  6. DeFelipe J and Farinas I 1992 The pyramidal neuron of the cerebral cortex: morphological and chemical characteristics of the synaptic inputs. Prog. Neurobiol. 39 563–607

  7. Delacourte A, David JP, Sergeant N, Buee L, Wattez A, Vermersch P, Ghozali F, Fallet-Bianco C, Pasquier F, Lebert F, Petit H and Di Menza C 1999 The biochemical pathway of neurofibrillary degeneration in aging and Alzheimer’s disease. Neurology 52 1158–1165

  8. Dwivedi V and Lakhotia SC 2016 Ayurvedic Amalaki Rasayana promotes improved stress tolerance and thus has anti-aging effects in Drosophila melanogaster. J. Biosci. 41 697–711

  9. Dwivedi V, Tripathi BK, Mutsuddi M and Lakhotia SC 2013 Ayurvedic Amalaki Rasayana and Rasa-sindoor suppress neurodegeneration in fly models of Huntington’s and Alzheimer’s diseases. Curr. Sci. 104 1711–1723

  10. Dwivedi V, Anandan EM, Mony RS, Muraleedharan TS, Valiathan MS, Mutsuddi M and Lakhotia SC 2012 In vivo effects of traditional Ayurvedic formulations in Drosophila melanogaster model relate with therapeutic applications. PLoS One 7 e37113

  11. Dwivedi V, Tiwary S and Lakhotia SC 2015 Suppression of induced but not developmental apoptosis in Drosophila by Ayurvedic Amalaki Rasayana and Rasa-sindoor. J Bbiosci. 40 281–297

  12. Eppersen Neil C, Haga C, Mason GF, Seller E, Gueorguieva R, Zhang W, Weiss E, Rothman DL and Krystal JH 2002 Cortical γ-aminobutyric acids levels across the menstrual cycle in healthy women and those with premenstrual dysphoric disorder: A proton magnetic resonance spectroscopy study. Arch. Gen. Psychiatry 59 851–858

  13. Fitzpatrick SM, Hetherington HP, Behar KL and Shulman RG 1990 The flux from glucose to glutamate in the rat brain in vivo as determined by 1H-observed, 13C-edited NMR spectroscopy. J. Cereb. Blood Flow Metab. 10 170–179

  14. Goedert M and Spillantini MG 2006 A century of Alzheimer’s disease. Science 314 777–781

  15. Hansen RA, Gartlehner G, Webb AP, Morgan LC, Moore CG and Jonas DE 2008 Efficacy and safety of donepezil, galantamine, and rivastigmine for the treatment of Alzheimer’s disease: a systematic review and meta-analysis. Clin Interv Aging 3 211–225

  16. Hardy J and Selkoe DJ 2002 The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297 353–356

  17. Hyder F, Patel AB, Gjedde A, Rothman DL, Behar KL and Shulman RG 2006 Neuronal-glial glucose oxidation and glutamatergic-GABAergic function. J. Cereb. Blood Flow Metab. 26 865–877

  18. Jankowsky JL, Fadale DJ, Anderson J, Xu GM, Gonzales V, Jenkins NA, Copeland NG, Lee MK, Younkin LH, Wagner SL, Younkin SG and Borchelt DR 2004 Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum. Mol. Genet. 13 159–170

  19. Lakhotia SC (2013) Neurodegeneration disorders need holistic care and treatment - can ayurveda meet the challenge? Ann Neurosci 20:1–2

  20. Mattson MP and Kater SB 1989 Excitatory and inhibitory neurotransmitters in the generation and degeneration of hippocampal neuroarchitecture. Brain Res. 478 337–348

  21. Morris RGM, Anderson E, Lynch GS and Baudry M 1986 Selective impairment of learning and blockade of long-term potentiation by an N-methyl-D-aspartate antagonist, AP5. Nature 329 774–776

  22. Ottersen OP and Storm-Mathisen J 1986 Excitatory amino acid pathways in the brain. Adv Exp Med Biol 203 263–284

  23. Patel AB, Rothman DL, Cline GW and Behar KL 2001 Glutamine is the major precursor for GABA synthesis in rat neocortex in vivo following acute GABA-transaminase inhibition. Brain Res. 919 207–220

  24. Patel AB, de Graaf RA, Mason GF, Rothman DL, Shulman RG and Behar KL 2005 The contribution of GABA to glutamate/glutamine cycling and energy metabolism in the rat cortex in vivo. Proc. Natl. Acad. Sci. USA 102 5588–5593

  25. Patel AB, de Graaf RA, Mason GF, Kanamatsu T, Rothman DL, Shulman RG and Behar KL 2004 Glutamatergic neurotransmission and neuronal glucose oxidation are coupled during intense neuronal activation. J. Cereb. Blood Flow Metab. 24 972–985

  26. Rabinovici GD, Furst AJ, Alkalay A, Racine CA, O’Neil JP, Janabi M, Baker SL, Agarwal N, Bonasera SJ, Mormino EC, Weiner MW, Gorno-Tempini ML, Rosen HJ, Miller BL and Jagust WJ 2010 Increased metabolic vulnerability in early-onset Alzheimer’s disease is not related to amyloid burden. Brain 133 512–528

  27. Sarkar PK and Chaudhary AK 2010 Ayurvedic Bhasma: the most ancient application of nanomedicine. J. Sci. Industr. Res. 69 901–915

  28. Schmidt WJ, Bubser M and Hauber W 1992 Behavioural pharmacology of glutamate in the basal ganglia. J. Neural Transm. Suppl. 38 65–89.

  29. Selkoe DJ 1998 The cell biology of beta-amyloid precursor protein and presenilin in Alzheimer’s disease. Trends Cell Biol. 8 447–453

  30. Sibson NR, Dhankhar A, Mason GF, Rothman DL, Behar KL and Shulman RG 1998 Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity. Proc. Natl. Acad. Sci. USA 95 316–321.

  31. Singh SK, Chaudhary AK, Rai DK and SB Rai 2009 Preparation and characterization of a mercury based Indian traditional drug Ras-sindoor. Indian J. Tradit. Knowl. 8 346–357

  32. Swain U, Sindhu KK, Boda U, Pothani S, Giridharan NV, Raghunath M and Rao KS 2012 Studies on the molecular correlates of genomic stability in rat brain cells following Amalakirasayana therapy. Mech. Ageing Dev. 133 112–117

  33. Tiwari V and Patel AB 2012 Impaired glutamatergic and GABAergic function at early age in AbetaPPswe-PS1dE9 mice: implications for Alzheimer’s disease. J. Alzheimers Dis. 28 765–769

  34. Tiwari V, Ambadipudi S and Patel AB 2013 Glutamatergic and GABAergic TCA cycle and neurotransmitter cycling fluxes in different regions of mouse brain. J. Cereb. Blood Flow Metab. 33 1523–1531

  35. Vorhees CV and Williams MT 2006 Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat. Protocol. 1 848–858

Download references

Acknowledgements

We thank Dr Robin A de Graff, Yale University, for providing the 1H-[13C]-NMR pulse sequence, and Mr Bhargidhar Babu for assistance in animal studies, Dr Swati Maitra for help in carrying out MWM experiments. We thank Prof MS Valiathan for initiating the coordinated studies on Science of Ayurveda, and Arya Vaidya Sala, Kottakal (Kerala, India) for providing the Amalaki Rasayana formulation. The Brain and Behavioral Experiment Facility is dully acknowledged for MWM test. All NMR experiments were performed at NMR Microimaging and Spectroscopy Facility, CCMB, Hyderabad, India. This study was supported by grants from the Department of Biotechnology (BT/PR14064/Med/30/359/2010), Department of Science and Technology (AB/013/2013), and CSIR network project BSC0208.

Author information

Correspondence to Anant B Patel.

Additional information

Corresponding editor: Neeraj Jain

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Tiwari, V., Saba, K., Veeraiah, P. et al. Amalaki Rasayana improved memory and neuronal metabolic activity in AβPP-PS1 mouse model of Alzheimer’s disease. J Biosci 42, 363–371 (2017). https://doi.org/10.1007/s12038-017-9692-7

Download citation

Keywords

  • Alzheimer’s disease
  • 13C nuclear magnetic
  • GABA
  • glutamate
  • neurotransmitter cycle
  • resonance spectroscopy