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Ashwagandha for Brain Health: Experimental Evidence for Its Neuroregenerative Activities

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Science of Ashwagandha: Preventive and Therapeutic Potentials

Abstract

Rapidly growing population, social and environmental factors are continuously exerting impact on social and psychological human health in multiple ways. In particular, these factors cause cumulative stress affecting cognitive functions and elevate risks of diverse neuronal dysfunction and malignant brain diseases. Maintenance of brain health has hence emerged as a new challenge in increasing old age populations worldwide. Use of herbal drug constituents has emerged as a preferred choice due to enormous undesirable side effects of pharmacological drugs. Ashwagandha, a sub-tropical medicinal plant has been extensively used in Indian traditional home medicine system i.e. called “Ayurveda” for its stress-, hypertension-, aging-, neurological dysfunction- and malignant growth-inhibitory properties. Detailed molecular insights of these activities and mechanism(s) are only beginning to be demonstrated by laboratory studies. In this chapter, we attempt to sketch research evidence of the benefits of Ashwagandha bioactives for brain health.

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References

  • Agnihotri AP, Sontakke SD, Thawani VR, Saoji A, Goswami VS (2013) Effects of Withania somnifera in patients of schizophrenia: a randomized, double blind, placebo controlled pilot trial study. Indian J Pharmacol 45:417–418

    Article  PubMed  PubMed Central  Google Scholar 

  • Ahmad M, Saleem S, Ahmad AS, Ansari MA, Yousuf S, Hoda MN, Islam F (2005) Neuroprotective effects of Withania somnifera on 6-hydroxydopamine induced Parkinsonism in rats. Hum Exp Toxicol 24:137–147

    Article  PubMed  Google Scholar 

  • Ahmad MK, Mahdi AA, Shukla KK, Islam N, Rajender S, Madhukar D, Shankhwar SN, Ahmad S (2010) Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males. Fertil Steril 94:989–996

    Article  PubMed  Google Scholar 

  • Ahmed ME, Javed H, Khan MM, Vaibhav K, Ahmad A, Khan A, Tabassum R, Islam F, Safhi MM, Islam F (2013) Attenuation of oxidative damage-associated cognitive decline by Withania somnifera in rat model of streptozotocin-induced cognitive impairment. Protoplasma 250:1067–1078

    Article  CAS  PubMed  Google Scholar 

  • Akula KK, Dhir A, Kulkarni SK (2009) Effect of various antiepileptic drugs in a pentylenetetrazol-induced seizure model in mice. Methods Find Exp Clin Pharmacol 31:423–432

    Article  CAS  PubMed  Google Scholar 

  • Ali SA, Meitei KV (2011) On the action and mechanism of withaferin-A from Withania somnifera, a novel and potent melanin dispersing agent in frog melanophores. J Recept Signal Transduct Res 31:359–366

    Article  CAS  PubMed  Google Scholar 

  • Andrade C (2009) Ashwagandha for anxiety disorders. World J Biol Psychiatry 10:686–687

    Article  PubMed  Google Scholar 

  • Antony ML, Lee J, Hahm ER, Kim SH, Marcus AI, Kumari V, Ji X, Yang Z, Vowell CL, Wipf P, Uechi GT, Yates NA, Romero G, Sarkar SN, Singh SV (2014) Growth arrest by the antitumor steroidal lactone withaferin A in human breast cancer cells is associated with down-regulation and covalent binding at cysteine 303 of beta-tubulin. J Biol Chem 289:1852–1865

    Article  CAS  PubMed  Google Scholar 

  • Anwer T, Sharma M, Pillai KK, Khan G (2012) Protective effect of Withania somnifera against oxidative stress and pancreatic beta-cell damage in type 2 diabetic rats. Acta Pol Pharm 69:1095–1101

    PubMed  Google Scholar 

  • Arvanitakis Z, Witte RJ, Dickson DW, Tsuboi Y, Uitti RJ, Slowinski J, Hutton ML, Lin SC, Boeve BF, Cheshire WP, Pooley RA, Liss JM, Caviness JN, Strongosky AJ, Wszolek ZK (2007) Clinical-pathologic study of biomarkers in FTDP-17 (PPND family with N279K tau mutation). Parkinsonism Relat Disord 13:230–239

    Article  PubMed  Google Scholar 

  • Baitharu I, Jain V, Deep SN, Hota KB, Hota SK, Prasad D, Ilavazhagan G (2013) Withania somnifera root extract ameliorates hypobaric hypoxia induced memory impairment in rats. J Ethnopharmacol 145:431–441

    Article  PubMed  Google Scholar 

  • Bhattacharya A, Ghosal S, Bhattacharya SK (2001) Anti-oxidant effect of Withania somnifera glycowithanolides in chronic footshock stress-induced perturbations of oxidative free radical scavenging enzymes and lipid peroxidation in rat frontal cortex and striatum. J Ethnopharmacol 74:1–6

    Article  CAS  PubMed  Google Scholar 

  • Bhattacharya A, Muruganandam AV, Kumar V, Bhattacharya SK (2002) Effect of poly herbal formulation, EuMil, on neurochemical perturbations induced by chronic stress. Indian J Exp Biol 40:1161–1163

    CAS  PubMed  Google Scholar 

  • Bhattacharya A, Ramanathan M, Ghosal S, Bhattacharya SK (2000a) Effect of Withania somnifera glycowithanolides on iron-induced hepatotoxicity in rats. Phytother Res 14:568–570

    Article  CAS  PubMed  Google Scholar 

  • Bhattacharya SK, Bhattacharya A, Chakrabarti A (2000b) Adaptogenic activity of Siotone, a polyherbal formulation of Ayurvedic rasayanas. Indian J Exp Biol 38:119–128

    CAS  PubMed  Google Scholar 

  • Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S (2000c) Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. Phytomedicine 7:463–469

    Article  CAS  PubMed  Google Scholar 

  • Bhattacharya SK, Muruganandam AV (2003) Adaptogenic activity of Withania somnifera: an experimental study using a rat model of chronic stress. Pharmacol Biochem Behav 75:547–555

    Article  CAS  PubMed  Google Scholar 

  • Boeve BF, Silber MH, Saper CB, Ferman TJ, Dickson DW, Parisi JE, Benarroch EE, Ahlskog JE, Smith GE, Caselli RC, Tippman-Peikert M, Olson EJ, Lin SC, Young T, Wszolek Z, Schenck CH, Mahowald MW, Castillo PR, Del Tredici K, Braak H (2007) Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain 130:2770–2788

    Article  CAS  PubMed  Google Scholar 

  • Chandrasekhar K, Kapoor J, Anishetty S (2012) A prospective, randomized double-blind, placebo-controlled study of safety and efficacy of a high-concentration full-spectrum extract of ashwagandha root in reducing stress and anxiety in adults. Indian J Psychol Med 34:255–262

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chatterjee S, Rao AT, Das SN, Agrawal SK (2001) Anti-atherogenic Action of “Cardipro” – A Herbal Proprietary Formulation. Anc Sci Life 20:81–85

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chaudhary G, Sharma U, Jagannathan NR, Gupta YK (2003) Evaluation of Withania somnifera in a middle cerebral artery occlusion model of stroke in rats. Clin Exp Pharmacol Physiol 30:399–404

    Article  CAS  PubMed  Google Scholar 

  • Chengappa KN, Bowie CR, Schlicht PJ, Fleet D, Brar JS, Jindal R (2013) Randomized placebo-controlled adjunctive study of an extract of withania somnifera for cognitive dysfunction in bipolar disorder. J Clin Psychiatry 74:1076–1083

    Article  PubMed  Google Scholar 

  • Choudhary MI, Nawaz SA, ul-Haq Z, Lodhi MA, Ghayur MN, Jalil S, Riaz N, Yousuf S, Malik A, Gilani AH, ur-Rahman A (2005) Withanolides, a new class of natural cholinesterase inhibitors with calcium antagonistic properties. Biochem Biophys Res Commun 334:276–287

    Article  CAS  PubMed  Google Scholar 

  • Choudhary MI, Yousuf S, Nawaz SA, Ahmed S, Atta ur R (2004) Cholinesterase inhibiting withanolides from Withania somnifera. Chem Pharm Bull (Tokyo) 52:1358–1361

    Article  CAS  Google Scholar 

  • Choudhary S, Kumar P, Malik J (2013) Plants and phytochemicals for Huntington’s disease. Pharmacogn Rev 7:81–91

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Cooley K, Szczurko O, Perri D, Mills EJ, Bernhardt B, Zhou Q, Seely D (2009) Naturopathic care for anxiety: a randomized controlled trial ISRCTN78958974. PLoS One 4:e6628

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dar PA, Singh LR, Kamal MA, Dar TA (2016) Unique Medicinal Properties of Withania Somnifera: Phytochemical Constituents and Protein Component. Curr Pharm Des 22:535–540

    Article  CAS  PubMed  Google Scholar 

  • Davis L, Kuttan G (1998) Suppressive effect of cyclophosphamide-induced toxicity by Withania somnifera extract in mice. J Ethnopharmacol 62:209–214

    Article  CAS  PubMed  Google Scholar 

  • Devi PU (1996) Withania somnifera Dunal (Ashwagandha): potential plant source of a promising drug for cancer chemotherapy and radiosensitization. Indian J Exp Biol 34:927–932

    CAS  PubMed  Google Scholar 

  • Felicio AC, Dinelle K, Agarwal PA, McKenzie J, Heffernan N, Road JD, Appel-Cresswell S, Wszolek ZK, Farrer MJ, Schulzer M, Sossi V, Stoessl AJ (2014) In vivo dopaminergic and serotonergic dysfunction in DCTN1 gene mutation carriers. Mov Disord 29:1197–1201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao R, Shah N, Lee JS, Katiyar SP, Li L, Oh E, Sundar D, Yun CO, Kaul SC, Wadhwa R (2014) Withanone Rich Combination of Ashwagandha Withanolides Restricts Metastasis And Angiogenesis Through hnRNP-K. Mol Cancer Ther 13:2930–2940

    Article  CAS  PubMed  Google Scholar 

  • Gautam A, Kaul SC, Thakur MK (2015) Alcoholic Extract of Ashwagandha Leaves Protects Against Amnesia by Regulation of Arc Function. Mol Neurobiol 53:1760–1769

    Article  PubMed  CAS  Google Scholar 

  • Gautam A, Wadhwa R, Thakur MK (2013) Involvement of hippocampal Arc in amnesia and its recovery by alcoholic extract of Ashwagandha leaves. Neurobiol Learn Mem 106:177–184

    Article  PubMed  Google Scholar 

  • Grin B, Mahammad S, Wedig T, Cleland MM, Tsai L, Herrmann H, Goldman RD (2012) Withaferin a alters intermediate filament organization, cell shape and behavior. PLoS One 7:e39065

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grover A, Shandilya A, Agrawal V, Bisaria VS, Sundar D (2012) Computational evidence to inhibition of human acetyl cholinesterase by withanolide a for Alzheimer treatment. J Biomol Struct Dyn 29:651–662

    Article  CAS  PubMed  Google Scholar 

  • Gupta GL, Rana AC (2008) Effect of Withania somnifera Dunal in ethanol-induced anxiolysis and withdrawal anxiety in rats. Indian J Exp Biol 46:470–475

    PubMed  Google Scholar 

  • Gupta SK, Mohanty I, Talwar KK, Dinda A, Joshi S, Bansal P, Saxena A, Arya DS (2004) Cardioprotection from ischemia and reperfusion injury by Withania somnifera: a hemodynamic, biochemical and histopathological assessment. Mol Cell Biochem 260:39–47

    Article  PubMed  Google Scholar 

  • Hynd MR, Scott HL, Dodd PR (2004) Glutamate-mediated excitotoxicity and neurodegeneration in Alzheimer’s disease. Neurochem Int 45:583–595

    Article  CAS  PubMed  Google Scholar 

  • Ichikawa H, Takada Y, Shishodia S, Jayaprakasam B, Nair MG, Aggarwal BB (2006) Withanolides potentiate apoptosis, inhibit invasion, and abolish osteoclastogenesis through suppression of nuclear factor-kappaB (NF-kappaB) activation and NF-kappaB-regulated gene expression. Mol Cancer Ther 5:1434–1445

    Article  CAS  PubMed  Google Scholar 

  • Jain S, Shukla SD, Sharma K, Bhatnagar M (2001) Neuroprotective effects of Withania somnifera Dunn. in hippocampal sub-regions of female albino rat. Phytother Res 15:544–548

    Article  CAS  PubMed  Google Scholar 

  • Jayaprakasam B, Padmanabhan K, Nair MG (2010) Withanamides in Withania somnifera fruit protect PC-12 cells from beta-amyloid responsible for Alzheimer’s disease. Phytother Res 24:859–863

    CAS  PubMed  Google Scholar 

  • Jena GB, Nemmani KV, Kaul CL, Ramarao P (2003) Protective effect of a polyherbal formulation (Immu-21) against cyclophosphamide-induced mutagenicity in mice. Phytother Res 17:306–310

    Article  CAS  PubMed  Google Scholar 

  • Kasture S, Vinci S, Ibba F, Puddu A, Marongiu M, Murali B, Pisanu A, Lecca D, Zernig G, Acquas E (2009) Withania somnifera prevents morphine withdrawal-induced decrease in spine density in nucleus accumbens shell of rats: a confocal laser scanning microscopy study. Neurotox Res 16:343–355

    Article  CAS  PubMed  Google Scholar 

  • Kataria H, Gupta M, Lakhman S, Kaur G (2015a) Withania somnifera aqueous extract facilitates the expression and release of GnRH: In vitro and in vivo study. Neurochem Int 89:111–119

    Article  CAS  PubMed  Google Scholar 

  • Kataria H, Kumar S, Chaudhary H, Kaur G (2015b) Withania somnifera Suppresses Tumor Growth of Intracranial Allograft of Glioma Cells. Mol Neurobiol 53:4143–4158

    Article  PubMed  CAS  Google Scholar 

  • Kataria H, Shah N, Kaul SC, Wadhwa R, Kaur G (2011) Water extract of ashwagandha leaves limits proliferation and migration, and induces differentiation in glioma cells. Evid Based Complement Alternat Med 2011:267614

    Article  PubMed  PubMed Central  Google Scholar 

  • Kataria H, Wadhwa R, Kaul SC, Kaur G (2012) Water extract from the leaves of Withania somnifera protect RA differentiated C6 and IMR-32 cells against glutamate-induced excitotoxicity. PLoS One 7:e37080

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kataria H, Wadhwa R, Kaul SC, Kaur G (2013) Withania somnifera water extract as a potential candidate for differentiation based therapy of human neuroblastomas. PLoS One 8:e55316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaur K, Rani G, Widodo N, Nagpal A, Taira K, Kaul SC, Wadhwa R (2004) Evaluation of the anti-proliferative and anti-oxidative activities of leaf extract from in vivo and in vitro raised Ashwagandha. Food Chem Toxicol 42:2015–2020

    Article  CAS  PubMed  Google Scholar 

  • Kaur P, Sharma M, Mathur S, Tiwari M, Divekar HM, Kumar R, Srivastava KK, Chandra R (2003) Effect of 1-oxo-5beta, 6beta-epoxy-witha-2-ene-27-ethoxy-olide isolated from the roots of Withania somnifera on stress indices in Wistar rats. J Altern Complement Med 9:897–907

    Article  PubMed  Google Scholar 

  • Kaurav BP, Wanjari MM, Chandekar A, Chauhan NS, Upmanyu N (2012) Influence of Withania somnifera on obsessive compulsive disorder in mice. Asian Pac J Trop Med 5:380–384

    Article  PubMed  Google Scholar 

  • Konar A, Shah N, Singh R, Saxena N, Kaul SC, Wadhwa R, Thakur MK (2011) Protective role of Ashwagandha leaf extract and its component withanone on scopolamine-induced changes in the brain and brain-derived cells. PLoS One 6:e27265

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krishnamurthy MN, Telles S (2007) Assessing depression following two ancient Indian interventions: effects of yoga and ayurveda on older adults in a residential home. J Gerontol Nurs 33:17–23

    PubMed  Google Scholar 

  • Kuboyama T, Tohda C, Komatsu K (2005) Neuritic regeneration and synaptic reconstruction induced by withanolide A. Br J Pharmacol 144:961–971

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuboyama T, Tohda C, Komatsu K (2006) Withanoside IV and its active metabolite, sominone, attenuate Abeta(25-35)-induced neurodegeneration. Eur J Neurosci 23:1417–1426

    Article  PubMed  Google Scholar 

  • Kuboyama T, Tohda C, Komatsu K (2014) Effects of Ashwagandha (roots of Withania somnifera) on neurodegenerative diseases. Biol Pharm Bull 37:892–897

    Article  CAS  PubMed  Google Scholar 

  • Kulkarni SK, Akula KK, Dhir A (2008a) Effect of Withania somnifera Dunal root extract against pentylenetetrazol seizure threshold in mice: possible involvement of GABAergic system. Indian J Exp Biol 46:465–469

    CAS  PubMed  Google Scholar 

  • Kulkarni SK, Dhir A (2008) Withania somnifera: an Indian ginseng. Prog Neuropsychopharmacol Biol Psychiatry 32:1093–1105

    Article  CAS  PubMed  Google Scholar 

  • Kulkarni SK, Singh K, Bishnoi M (2008b) Comparative behavioural profile of newer antianxiety drugs on different mazes. Indian J Exp Biol 46:633–638

    CAS  PubMed  Google Scholar 

  • Kumar A, Kalonia H (2007) Protective effect of Withania somnifera Dunal on the behavioral and biochemical alterations in sleep-disturbed mice (Grid over water suspended method). Indian J Exp Biol 45:524–528

    PubMed  Google Scholar 

  • Kumar A, Kalonia H (2008) Effect of Withania somnifera on Sleep-Wake Cycle in Sleep-Disturbed Rats: Possible GABAergic Mechanism. Indian J Pharm Sci 70:806–810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumar A, Kulkarni SK (2006) Effect of BR-16A (Mentat), a polyherbal formulation on drug-induced catalepsy in mice. Indian J Exp Biol 44:45–48

    PubMed  Google Scholar 

  • Kumar P, Kumar A (2009) Possible neuroprotective effect of Withania somnifera root extract against 3-nitropropionic acid-induced behavioral, biochemical, and mitochondrial dysfunction in an animal model of Huntington’s disease. J Med Food 12:591–600

    Article  CAS  PubMed  Google Scholar 

  • Kumar P, Singh R, Nazmi A, Lakhanpal D, Kataria H, Kaur G (2014) Glioprotective Effects of Ashwagandha Leaf Extract against Lead Induced Toxicity. Biomed Res Int 2014:182029

    PubMed  PubMed Central  Google Scholar 

  • Kumar S, Seal CJ, Howes MJ, Kite GC, Okello EJ (2010) In vitro protective effects of Withania somnifera (L.) dunal root extract against hydrogen peroxide and beta-amyloid(1-42)-induced cytotoxicity in differentiated PC12 cells. Phytother Res 24:1567–1574

    Article  CAS  PubMed  Google Scholar 

  • Kumar V, Murthy KN, Bhamid S, Sudha CG, Ravishankar GA (2005) Genetically modified hairy roots of Withania somnifera Dunal: a potent source of rejuvenating principles. Rejuvenation Res 8:37–45

    Article  CAS  PubMed  Google Scholar 

  • Kurapati KR, Atluri VS, Samikkannu T, Nair MP (2013) Ashwagandha (Withania somnifera) reverses beta-amyloid1-42 induced toxicity in human neuronal cells: implications in HIV-associated neurocognitive disorders (HAND). PLoS One 8:e77624

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kurapati KR, Samikkannu T, Atluri VS, Kaftanovskaya E, Yndart A, Nair MP (2014) beta-Amyloid1-42, HIV-1Ba-L (clade B) infection and drugs of abuse induced degeneration in human neuronal cells and protective effects of ashwagandha (Withania somnifera) and its constituent Withanolide A. PLoS One 9:e112818

    Google Scholar 

  • Kuttan G (1996) Use of Withania somnifera Dunal as an adjuvant during radiation therapy. Indian J Exp Biol 34:854–856

    CAS  PubMed  Google Scholar 

  • Lee DH, Lim IH, Sung EG, Kim JY, Song IH, Park YK, Lee TJ (2013a) Withaferin A inhibits matrix metalloproteinase-9 activity by suppressing the Akt signaling pathway. Oncol Rep 30:933–938

    Article  CAS  PubMed  Google Scholar 

  • Lee J, Hahm ER, Marcus AI, Singh SV (2013b) Withaferin A inhibits experimental epithelial-mesenchymal transition in MCF-10A cells and suppresses vimentin protein level in vivo in breast tumors. Mol Carcinog 54:417–429

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee J, Sehrawat A, Singh SV (2012) Withaferin A causes activation of Notch2 and Notch4 in human breast cancer cells. Breast Cancer Res Treat 136:45–56

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Maity T, Adhikari A, Bhattacharya K, Biswas S, Debnath PK, Maharana CS (2011) A study on evalution of antidepressant effect of imipramine adjunct with Aswagandha and Bramhi. Nepal Med Coll J 13:250–253

    CAS  PubMed  Google Scholar 

  • Manjunath MJ, Muralidhara (2013) Effect of Withania somnifera supplementation on rotenone-induced oxidative damage in cerebellum and striatum of the male mice brain. Cent Nerv Syst Agents Med Chem 13:43–56

    Article  CAS  PubMed  Google Scholar 

  • Manjunath NK, Telles S (2005) Influence of Yoga and Ayurveda on self-rated sleep in a geriatric population. Indian J Med Res 121:683–690

    CAS  PubMed  Google Scholar 

  • Mirjalili MH, Moyano E, Bonfill M, Cusido RM, Palazon J (2009) Steroidal lactones from Withania somnifera, an ancient plant for novel medicine. Molecules 14:2373–2393

    Article  CAS  PubMed  Google Scholar 

  • Misra DS, Maiti R, Ghosh D (2009) Protection of swimming-induced oxidative stress in some vital organs by the treatment of composite extract of Withania somnifera, Ocimum sanctum and Zingiber officinalis in male rat. Afr J Tradit Complement Altern Med 6:534–543

    PubMed  PubMed Central  Google Scholar 

  • Mohan L, Rao US, Gopalakrishna HN, Nair V (2011) Evaluation of the Anxiolytic Activity of NR-ANX-C (a Polyherbal Formulation) in Ethanol Withdrawal-Induced Anxiety Behavior in Rats. Evid Based Complement Alternat Med 2011:2011

    Google Scholar 

  • Mohanty IR, Arya DS, Gupta SK (2008) Withania somnifera provides cardioprotection and attenuates ischemia-reperfusion induced apoptosis. Clin Nutr 27:635–642

    Article  PubMed  Google Scholar 

  • Muruganandam AV, Kumar V, Bhattacharya SK (2002) Effect of poly herbal formulation, EuMil, on chronic stress-induced homeostatic perturbations in rats. Indian J Exp Biol 40:1151–1160

    CAS  PubMed  Google Scholar 

  • Nagashayana N, Sankarankutty P, Nampoothiri MR, Mohan PK, Mohanakumar KP (2000) Association of L-DOPA with recovery following Ayurveda medication in Parkinson’s disease. J Neurol Sci 176:124–127

    Article  CAS  PubMed  Google Scholar 

  • Naidu PS, Singh A, Kulkarni SK (2003) Effect of Withania somnifera root extract on haloperidol-induced orofacial dyskinesia: possible mechanisms of action. J Med Food 6:107–114

    Article  PubMed  Google Scholar 

  • Naidu PS, Singh A, Kulkarni SK (2006) Effect of Withania somnifera root extract on reserpine-induced orofacial dyskinesia and cognitive dysfunction. Phytother Res 20:140–146

    Article  PubMed  Google Scholar 

  • Nair V, Arjuman A, Dorababu P, Gopalakrishna HN, Chakradhar Rao U, Mohan L (2007) Effect of NR-ANX-C (a polyherbal formulation) on haloperidol induced catalepsy in albino mice. Indian J Med Res 126:480–484

    CAS  PubMed  Google Scholar 

  • Nair V, Arjuman A, Gopalakrishna HN, Nandini M (2008) Effect of Withania somnifera root extract on haloperidol-induced catalepsy in albino mice. Phytother Res 22:243–246

    Article  PubMed  Google Scholar 

  • Nandhagopal R, Mak E, Schulzer M, McKenzie J, McCormick S, Sossi V, Ruth TJ, Strongosky A, Farrer MJ, Wszolek ZK, Stoessl AJ (2008) Progression of dopaminergic dysfunction in a LRRK2 kindred: a multitracer PET study. Neurology 71:1790–1795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Parihar MS, Chaudhary M, Shetty R, Hemnani T (2004) Susceptibility of hippocampus and cerebral cortex to oxidative damage in streptozotocin treated mice: prevention by extracts of Withania somnifera and Aloe vera. J Clin Neurosci 11:397–402

    Article  CAS  PubMed  Google Scholar 

  • Parihar MS, Hemnani T (2003) Phenolic antioxidants attenuate hippocampal neuronal cell damage against kainic acid induced excitotoxicity. J Biosci 28:121–128

    Article  CAS  PubMed  Google Scholar 

  • Patil SP, Maki S, Khedkar SA, Rigby AC, Chan C (2010) Withanolide A and asiatic acid modulate multiple targets associated with amyloid-beta precursor protein processing and amyloid-beta protein clearance. J Nat Prod 73:1196–1202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pingali U, Pilli R, Fatima N (2014) Effect of standardized aqueous extract of Withania somnifera on tests of cognitive and psychomotor performance in healthy human participants. Pharmacognosy Res 6:12–18

    Article  PubMed  PubMed Central  Google Scholar 

  • Prakash J, Yadav SK, Chouhan S, Singh SP (2013) Neuroprotective role of Withania somnifera root extract in maneb-paraquat induced mouse model of parkinsonism. Neurochem Res 38:972–980

    Article  CAS  PubMed  Google Scholar 

  • Pramanik SS, Sur TK, Debnath PK, Bhattacharyya D (2010) Effect of Pueraria tuberosa tuber extract on chronic foot shock stress in Wistar rats. Nepal Med Coll J 12:234–238

    CAS  PubMed  Google Scholar 

  • Prasad S, Malhotra CL (1968) Studies on Withania ashwagandha Kaul. VI. The effect of the alkaloidal fractions (acetone, alcohol and water soluble) on the central nervous system. Indian J Physiol Pharmacol 12:175–181

    CAS  PubMed  Google Scholar 

  • Praveenkumar V, Kuttan R, Kuttan G (1994) Chemoprotective action of Rasayanas against cyclosphamide toxicity. Tumori 80:306–308

    CAS  PubMed  Google Scholar 

  • Priyandoko D, Ishii T, Kaul SC, Wadhwa R (2011) Ashwagandha leaf derived withanone protects normal human cells against the toxicity of methoxyacetic acid, a major industrial metabolite. PLoS One 6:e19552

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Raghavan A, Shah ZA (2014) Withania somnifera Improves Ischemic Stroke Outcomes by Attenuating PARP1-AIF-Mediated Caspase-Independent Apoptosis. Mol Neurobiol 52:1093–1105

    Article  PubMed  CAS  Google Scholar 

  • RajaSankar S, Manivasagam T, Sankar V, Prakash S, Muthusamy R, Krishnamurti A, Surendran S (2009a) Withania somnifera root extract improves catecholamines and physiological abnormalities seen in a Parkinson’s disease model mouse. J Ethnopharmacol 125:369–373

    Google Scholar 

  • Rajasankar S, Manivasagam T, Surendran S (2009b) Ashwagandha leaf extract: a potential agent in treating oxidative damage and physiological abnormalities seen in a mouse model of Parkinson’s disease. Neurosci Lett 454:11–15

    Article  CAS  PubMed  Google Scholar 

  • Ramanathan M, Balaji B, Justin A (2011) Behavioural and neurochemical evaluation of Perment an herbal formulation in chronic unpredictable mild stress induced depressive model. Indian J Exp Biol 49:269–275

    CAS  PubMed  Google Scholar 

  • Rasheed A, Satyanarayana KV, Gulabi PS, Rao MS (2013) Chemical and pharmacological standardization of Ashwagandhadi lehyam: an ayurvedic formulation. J Complement Integr Med 15:10

    Google Scholar 

  • Raut AA, Rege NN, Tadvi FM, Solanki PV, Kene KR, Shirolkar SG, Pandey SN, Vaidya RA, Vaidya AB (2012) Exploratory study to evaluate tolerability, safety, and activity of Ashwagandha (Withania somnifera) in healthy volunteers. J Ayurveda Integr Med 3:111–114

    Article  PubMed  PubMed Central  Google Scholar 

  • Reuland DJ, Khademi S, Castle CJ, Irwin DC, McCord JM, Miller BF, Hamilton KL (2013) Upregulation of phase II enzymes through phytochemical activation of Nrf2 protects cardiomyocytes against oxidant stress. Free Radic Biol Med 56:102–111

    Article  CAS  PubMed  Google Scholar 

  • Ross OA, Soto-Ortolaza AI, Heckman MG, Verbeeck C, Serie DJ, Rayaprolu S, Rich SS, Nalls MA, Singleton A, Guerreiro R, Kinsella E, Wszolek ZK, Brott TG, Brown RD Jr, Worrall BB, Meschia JF (2013) NOTCH3 variants and risk of ischemic stroke. PLoS One 8:e75035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Russo A, Izzo AA, Cardile V, Borrelli F, Vanella A (2001) Indian medicinal plants as antiradicals and DNA cleavage protectors. Phytomedicine 8:125–132

    Article  CAS  PubMed  Google Scholar 

  • Sankar SR, Manivasagam T, Krishnamurti A, Ramanathan M (2007) The neuroprotective effect of Withania somnifera root extract in MPTP-intoxicated mice: an analysis of behavioral and biochemical variables. Cell Mol Biol Lett 12:473–481

    Article  CAS  PubMed  Google Scholar 

  • Sarris J, McIntyre E, Camfield DA (2013) Plant-based medicines for anxiety disorders, part 2: a review of clinical studies with supporting preclinical evidence. CNS Drugs 27:301–319

    Article  CAS  PubMed  Google Scholar 

  • Schliebs R, Liebmann A, Bhattacharya SK, Kumar A, Ghosal S, Bigl V (1997) Systemic administration of defined extracts from Withania somnifera (Indian Ginseng) and Shilajit differentially affects cholinergic but not glutamatergic and GABAergic markers in rat brain. Neurochem Int 30:181–190

    Article  CAS  PubMed  Google Scholar 

  • Sehgal N, Gupta A, Valli RK, Joshi SD, Mills JT, Hamel E, Khanna P, Jain SC, Thakur SS, Ravindranath V (2012) Withania somnifera reverses Alzheimer’s disease pathology by enhancing low-density lipoprotein receptor-related protein in liver. Proc Natl Acad Sci U S A 109:3510–3515

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shah N, Kataria H, Kaul SC, Ishii T, Kaur G, Wadhwa R (2009) Effect of the alcoholic extract of Ashwagandha leaves and its components on proliferation, migration, and differentiation of glioblastoma cells: combinational approach for enhanced differentiation. Cancer Sci 100:1740–1747

    Article  CAS  PubMed  Google Scholar 

  • Shah N, Singh R, Sarangi U, Saxena N, Chaudhary A, Kaur G, Kaul SC, Wadhwa R (2015) Combinations of Ashwagandha Leaf Extracts Protect Brain-Derived Cells against Oxidative Stress and Induce Differentiation. PLoS One 10:e0120554

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Shreevathsa M, Ravishankar B, Dwivedi R (2013) Anti depressant activity of Mamsyadi Kwatha: An Ayurvedic compound formulation. Ayu 34:113–117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shukla K, Dikshit P, Tyagi MK, Shukla R, Gambhir JK (2012) Ameliorative effect of Withania coagulans on dyslipidemia and oxidative stress in nicotinamide-streptozotocin induced diabetes mellitus. Food Chem Toxicol 50:3595–3599

    Article  CAS  PubMed  Google Scholar 

  • Shukla KK, Mahdi AA, Mishra V, Rajender S, Sankhwar SN, Patel D, Das M (2011a) Withania somnifera improves semen quality by combating oxidative stress and cell death and improving essential metal concentrations. Reprod Biomed Online 22:421–427

    Article  PubMed  Google Scholar 

  • Shukla V, Mishra SK, Pant HC (2011b) Oxidative stress in neurodegeneration. Adv Pharmacol Sci 2011:572634

    PubMed  PubMed Central  Google Scholar 

  • Singh A, Naidu PS, Gupta S, Kulkarni SK (2002) Effect of natural and synthetic antioxidants in a mouse model of chronic fatigue syndrome. J Med Food 5:211–220

    Article  CAS  PubMed  Google Scholar 

  • Singh N, Bhalla M, de Jager P, Gilca M (2011) An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med 8:208–213

    PubMed  PubMed Central  Google Scholar 

  • Singh RH, Narsimhamurthy K, Singh G (2008) Neuronutrient impact of Ayurvedic Rasayana therapy in brain aging. Biogerontology 9:369–374

    Article  PubMed  Google Scholar 

  • Soman S, Anju TR, Jayanarayanan S, Antony S, Paulose CS (2013) Impaired motor learning attributed to altered AMPA receptor function in the cerebellum of rats with temporal lobe epilepsy: ameliorating effects of Withania somnifera and withanolide A. Epilepsy Behav 27:484–491

    Article  PubMed  Google Scholar 

  • Soman S, Korah PK, Jayanarayanan S, Mathew J, Paulose CS (2012) Oxidative stress induced NMDA receptor alteration leads to spatial memory deficits in temporal lobe epilepsy: ameliorative effects of Withania somnifera and Withanolide A. Neurochem Res 37:1915–1927

    Article  CAS  PubMed  Google Scholar 

  • Spector AR, Dugger BN, Wszolek ZK, Uitti RJ, Fredrickson P, Kaplan J, Boeve BF, Dickson DW, Strongosky A, Lin SC (2011) Anatomy of disturbed sleep in pallido-ponto-nigral degeneration. Ann Neurol 69:1014–1025

    Article  PubMed  PubMed Central  Google Scholar 

  • Thaiparambil JT, Bender L, Ganesh T, Kline E, Patel P, Liu Y, Tighiouart M, Vertino PM, Harvey RD, Garcia A, Marcus AI (2011) Withaferin A inhibits breast cancer invasion and metastasis at sub-cytotoxic doses by inducing vimentin disassembly and serine 56 phosphorylation. Int J Cancer 129:2744–2755

    Article  CAS  PubMed  Google Scholar 

  • Tohda C (2008) Overcoming several neurodegenerative diseases by traditional medicines: the development of therapeutic medicines and unraveling pathophysiological mechanisms. Yakugaku Zasshi 128:1159–1167

    Article  CAS  PubMed  Google Scholar 

  • Tohda C, Joyashiki E (2009) Sominone enhances neurite outgrowth and spatial memory mediated by the neurotrophic factor receptor, RET. Br J Pharmacol 157:1427–1440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tripathi AK, Dey S, Singh RH, Dey PK (1998) Alterations in the sensitivity of 5(th) receptor subtypes following chronic asvagandha treatment in rats. Anc Sci Life 17:169–181

    CAS  PubMed  PubMed Central  Google Scholar 

  • Uitti RJ, Wszolek ZK (2003) Dopamine agonists, sleep disorders, and driving in Parkinson’s disease. Adv Neurol 91:343–349

    CAS  PubMed  Google Scholar 

  • Vareed SK, Bauer AK, Nair KM, Liu Y, Jayaprakasam B, Nair MG (2014) Blood-Brain Barrier Permeability of Bioactive Withanamides Present in Withania somnifera Fruit Extract. Phytother Res 28:1260–1264

    Article  CAS  PubMed  Google Scholar 

  • Vedi M, Rasool M, Sabina EP (2014) Protective effect of administration of Withania somifera against bromobenzene induced nephrotoxicity and mitochondrial oxidative stress in rats. Ren Fail 36:1095–1103

    Article  CAS  PubMed  Google Scholar 

  • Ven Murthy MR, Ranjekar PK, Ramassamy C, Deshpande M (2010) Scientific basis for the use of Indian ayurvedic medicinal plants in the treatment of neurodegenerative disorders: ashwagandha. Cent Nerv Syst Agents Med Chem 10:238–246

    Article  CAS  PubMed  Google Scholar 

  • Wscieklica T, de Barros VM, Le Sueur ML, Pouza KC, Spadari RC, Cespedes IC (2016) Alcohol consumption increases locomotion in an open field and induces Fos-immunoreactivity in reward and approach/withdrawal-related neurocircuitries. Alcohol 50:73–82

    Article  CAS  PubMed  Google Scholar 

  • Yang Z, Garcia A, Xu S, Powell DR, Vertino PM, Singh S, Marcus AI (2013) Withania somnifera root extract inhibits mammary cancer metastasis and epithelial to mesenchymal transition. PLoS One 8:e75069

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yin H, Cho DH, Park SJ, Han SK (2013) GABA-mimetic actions of Withania somnifera on substantia gelatinosa neurons of the trigeminal subnucleus caudalis in mice. Am J Chin Med 41:1043–1051

    Article  PubMed  Google Scholar 

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Wadhwa, R., Kalra, R.S., Chaudhary, A., Kaul, S.C. (2017). Ashwagandha for Brain Health: Experimental Evidence for Its Neuroregenerative Activities. In: Kaul, S., Wadhwa, R. (eds) Science of Ashwagandha: Preventive and Therapeutic Potentials. Springer, Cham. https://doi.org/10.1007/978-3-319-59192-6_14

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