Potential clinical applications of Ashwagandha (Withania somnifera) in medicine and neuropsychiatry

References

• Hoenders HJR, Bartels-Velthuis AA, Vollbehr NK, et al. Natural medicines for psychotic disorders. J Nerv Ment Dis. 2018;206(2):81–101.
   Google Scholar
• Kumar S, Dobos GJ, Rampp T. The significance of ayurvedic medicinal plants. J Evid Based Complementary Altern Med. 2017;22(3):494–501.
   Google Scholar
• Chatterjee SS. From covalent bonds to eco-physiological pharmacology of secondary plant metabolites. Biochem Pharmacol. 2015;98(2):269–277.
   Google Scholar
• Andrade C. Research of Ayurvedic medicines. Ayurmedline. 2000;147–151.
   Google Scholar
• Rao SKR. Mental health in Ayurveda. Bangalore: NIMHANS; 1990.
   Google Scholar
• Sahoo N, Manchikanti P. Herbal drug regulation and commercialization: an Indian industry perspective. J Altern Complement Med. 2013;19(12):957–963.
   Google Scholar
• Sharma AK, Kumar R, Mishra A, et al. Problems associated with clinical trials of Ayurvedic medicines. Revista Brasileira de Farmacognosia. 2010;20(2):276–281.
   Google Scholar
• Parasuraman S, Thing GS, Dhanaraj SA. Polyherbal formulation: concept of Ayurveda. Pharmacogn Rev. 2014;8(16):73–80.
   Google Scholar
• World Health Organization. Traditional and complementary medicine in primary health care. Genève: WHO; 2018. p. 16. Available from: https://www.who.int/publications-detail-redirect/WHO-HIS-SDS-2018.37
   Google Scholar
• World Health Organization. WHO traditional medicine strategy 2014 - 2023. Genève: WHO; 2013. 76 p. Available from: https://www.who.int/publications/i/item/9789241506096
   Google Scholar
• Bharti VK, Malik JK, Gupta RC. Chapter 52 - Ashwagandha: multiple health benefits. In: Gupta RC, editor. Nutraceuticals [Internet]. Boston: Academic Press; 2016. p. 717–733. Available from: https://www.sciencedirect.com/science/article/pii/B9780128021477000528
   Google Scholar
• Ven Murthy MR, Ranjekar PK, Ramassamy C, et al. Scientific basis for the use of Indian ayurvedic medicinal plants in the treatment of neurodegenerative disorders: ashwagandha. Cent Nerv Syst Agents Med Chem. 2010;10(3):238–246.
   Google Scholar
• Mirjalili MH, Fakhr-Tabatabaei SM, Alizadeh H, et al. Genetic and withaferin A analysis of Iranian natural populations of Withania somnifera and W. coagulans by RAPD and HPTLC. Nat Product Com. 2009;4(3):337–346.
   Google Scholar
• Scartezzini P, Antognoni F, Conte L, et al. Genetic and phytochemical difference between some Indian and Italian plants of Withania somnifera (L.) Dunal. Nat Prod Res. 2007;21(10):923–932.
   Google Scholar
• Baliga MS, Meera S, Shivashankara AR, et al. Chapter 16 - The health benefits of Indian traditional ayurvedic rasayana (anti-aging) drugs: a review; 2015.shttps://www.sciencedirect.com/science/article/pii/B9780124186804000166
   Google Scholar
• Gupta SK, Dua A, Vohra BP. Withania somnifera (Ashwagandha) attenuates antioxidant defense in aged spinal cord and inhibits copper induced lipid peroxidation and protein oxidative modifications. Drug Metabol Drug Interact. 2003;19(3):211–222.
   Google Scholar
• Singh N, Bhalla M, de Jager P, et al. An overview on ashwagandha: a rasayana (rejuvenator) of ayurveda. Afr J Traditional Complementary Altern Med [Internet]. 2011;8(5S). Available from: https://www.ajol.info/index.php/ajtcam/article/view/67963
   Google Scholar
• Abou-Douh AM. New withanolides and other constituents from the fruit of Withania somnifera. Arch Pharm (Weinheim). 2002;335(6):267–276.
   Google Scholar
• Chatterjee S, Srivastava S, Khalid A, et al. Comprehensive metabolic fingerprinting of Withania somnifera leaf and root extracts. Phytochemistry. 2010;71(10):1085–1094.
   Google Scholar
• Deepa M, Veerabasappa Gowda T. Purification and characterization of a glycoprotein inhibitor of toxic phospholipase from Withania somnifera. Arch Biochem Biophys. 2002;408(1):42–50.
   Google Scholar
• Bassareo V, Talani G, Frau R, et al. Inhibition of morphine-and ethanol-mediated stimulation of mesolimbic dopamine neurons by Withania somnifera. Front Neurosci. 2019;13:545.
   Google Scholar
• Mehta AK, Binkley P, Gandhi SS, et al. Pharmacological effects of Withania somnifera root extract on GABA-A receptor complex. Indian J Med Res. 1991;94:312–315. Available from: https://pubmed.ncbi.nlm.nih.gov/1660034/
   Google Scholar
• Bhattarai JP, Ah Park S, Han SK. The methanolic extract of Withania somnifera ACTS on GABAA receptors in gonadotropin releasing hormone (GnRH) neurons in mice. Phytother Res. 2010;24(8):1147–1150.
   Google Scholar
• Yin H, Cho DH, Park SJ, et al. GABA-mimetic actions of Withania somnifera on substantia gelatinosa neurons of the trigeminal subnucleus caudalis in mice. Am J Chin Med. 2013;41(5):1043–1051.
   Google Scholar
• Kulkarni SK, George B, Nayar U. Amygdaloid kindling in rats: protective effect of Withania somnifera (Aswagandha) root extract. Indian Drugs. 1994;32:37–49.
   Google Scholar
• Kulkarni SK, Akula KK, Dhir A. Effect of Withania somnifera Dunal root extract against pentylenetetrazol seizure threshold in mice: possible involvement of GABAergic system. Indian J Exp Biol. 2008;46(6):465–469. Available fromhttps://pubmed.ncbi.nlm.nih.gov/18697606/
   Google Scholar
• Kulkarni SK, George B. Anticonvulsant action of Withania somnifera (Aswagandha) root extract against pentylenetetrazol-induced kindling in mice. Phytother Res. 1996;10(5):447–449.
   Google Scholar
• Kulkarni SK, Sharma A, Verma A, et al. GABA receptor mediated anticonvulsant action of Withania somnifera root extract. Indian Drugs. 1993;30:305–312. Available from: http://works.bepress.com/avadhesh_sharma/55/
   Google Scholar
• Shah N, Singh R, Sarangi U, et al. Combinations of Ashwagandha leaf extracts protect brain-derived cells against oxidative stress and induce differentiation. PLoS One. 2015;10(3):e0120554.
   Google Scholar
• Soman S, Korah PK, Jayanarayanan S, et al. 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. 2012;37(9):1915–1927.
   Google Scholar
• Bhattarai JP, Park SJ, Han SK. Potentiation of NMDA receptors by Withania somnifera on hippocampal CA1 pyramidal neurons. Am J Chin Med. 2013;41(3):503–513.
   Google Scholar
• Suganya K, Kayalvizhi E, Yuvaraj R, et al. Effect of Withania Somnifera on the antioxidant and neurotransmitter status in sleep deprivation induced Wistar rats. Bioinformation. 2020;16(8):631–637. Available from: http://www.bioinformation.net/016/97320630016631.htm
   Google Scholar
• Bhatnagar M, Sisodia SS, Bhatnagar R. Antiulcer and antioxidant activity of Asparagus racemosus WILLD and Withania somnifera DUNAL in Rats. Ann N Y Acad Sci. 2005;1056(1):261–278.
   Google Scholar
• Tripathi AK, Dey S, Singh RH, et al. Alterations in the sensitivity of 5-HT receptor subtypes following chronic asvagandha treatment in rats. Ancient Science of Life. 1998;17(3):169–181. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3331105/
   Google Scholar
• Kaurav BP, Wanjari MM, Chandekar A, et al. Influence of Withania somnifera on obsessive compulsive disorder in mice. Asian Pac J Trop Med. 2012;5(5):380–384.
   Google Scholar
• Choudhary MI, Yousuf S, Nawaz SA, et al. Cholinesterase inhibiting withanolides from Withania somnifera. Chem Pharm Bull. (Tokyo) 2004;52(11):1358–1361.
   Google Scholar
• Choudhary MI, Nawaz SA, ul-Haq Z, et al. Withanolides, a new class of natural cholinesterase inhibitors with calcium antagonistic properties. Biochem Biophys Res Commun. 2005;334(1):276–287.
   Google Scholar
• Gautam A, Wadhwa R, Thakur MK. Assessment of cholinergic properties of Ashwagandha leaf-extract in the amnesic mouse brain.Ann Neurosci. 2016;23(2):68–75.
   Google Scholar
• Bhatnagar M, Sharma D, Salvi M. Neuroprotective effects of Withania somnifera dunal. A possible mechanism. Neurochem Res. 2009;34(11):1975–1983.
   Google Scholar
• Schliebs R, Liebmann A, Bhattacharya SK, et al. 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. 1997;30(2):181–190.
   Google Scholar
• Borrás S, Martínez-Solís I, Ríos JL. Medicinal plants for insomnia related to anxiety: an updated review. Planta Med. 2021;87(10/11):738–753.
   Google Scholar
• Parihar MS, Chaudhary M, Shetty R, et al. 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. 2004;11(4):397–402.
   Google Scholar
• Jain S, Shukla SD, Sharma K, et al. Neuroprotective effects of Withania somnifera Dunn. in hippocampal sub-regions of female albino rat. Phytother Res. 2001;15(6):544–548.
   Google Scholar
• Zhao J, Nakamura N, Hattori M, et al. Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities. Chem Pharm Bull. 2002;50(6):760–765.
   Google Scholar
• Kuboyama T, Tohda C, Komatsu K. Neuritic regeneration and synaptic reconstruction induced by withanolide A. Br J Pharmacol. 2005;144(7):961–971.
   Google Scholar
• Tohda C, Kuboyama T, Komatsu K. Dendrite extension by methanol extract of Ashwagandha (roots of Withania somnifera) in SK-N-SH cells. Neuroreport. 2000;11(9):1981–1985.
   Google Scholar
• Tohda C, Kuboyama T, Komatsu K. Search for natural products related to regeneration of the neuronal network. Neurosignals. 2005;14(1–2):34–45.
   Google Scholar
• Tohda C. Overcoming several neurodegenerative diseases by traditional medicines: the development of therapeutic medicines and unraveling pathophysiological mechanisms [Article in Japanese]. Yakugaku Zasshi. 2008;128(8):1159–1167.
   Google Scholar
• Kuboyama T, Tohda C, Komatsu K. Neuritic regeneration and synaptic reconstruction induced by withanolide A. Br J Pharmacol. 2005;144(7):961–971.
   Google Scholar
• Ng QX, Loke W, Foo NX, et al. A systematic review of the clinical use of Withania somnifera (Ashwagandha) to ameliorate cognitive dysfunction. Phytother Res. 2020;34(3):583–590.
   Google Scholar
• Kumar S, Harris RJ, Seal CJ, et al. An aqueous extract of Withania somnifera root inhibits amyloid β fibril formation in vitro. Phytother Res. 2012;26(1):113–117.
   Google Scholar
• Sehgal N, Gupta A, Valli RK, et al. Withania somnifera reverses Alzheimer’s disease pathology by enhancing low-density lipoprotein receptor-related protein in liver. Pnas. 2012;109(9):3510–3515.
   Google Scholar
• Sood A, Mehrotra A, Dhawan DK, et al. Indian Ginseng (Withania somnifera) supplementation ameliorates oxidative stress and mitochondrial dysfunctions in experimental model of stroke. Metab Brain Dis. 2018;33(4):1261–1274.
   Google Scholar
• Kurapati KR, Atluri VS, Samikkannu T, et al.Ashwagandha (Withania somnifera) reverses β-amyloid1-42 induced toxicity in human neuronal cells: implications in HIV-associated neurocognitive disorders (HAND). PLoS One. 2013;8(10):e77624.
   Google Scholar
• Joshi T, Kumar V, Kaznacheyeva EV, et al. Withaferin A induces heat shock response and ameliorates disease progression in a mouse model of Huntington’s disease. Mol Neurobiol. 2021;58(8):3992–4006.
   Google Scholar
• Abdul-Latif R, Stupans I, Allahham A, et al. Natural antioxidants in the management of Parkinson’s disease: review of evidence from cell line and animal models. J Integr Med. 2021;19(4):300–310.
   Google Scholar
• Ahmad M, Saleem S, Ahmad AS, et al. Neuroprotective effects of Withania somnifera on 6-hydroxydopamine induced Parkinsonism in rats. Hum Exp Toxicol. 2005;24(3):137–147.
   Google Scholar
• Rath SN, Jena L, Bhuyan R, et al. In silico discovery and evaluation of phytochemicals binding mechanism against human catechol-O-methyltransferase as a putative bioenhancer of L-DOPA therapy in Parkinson disease. Genomics Inform. 2021;19(1):e7.
   Google Scholar
• Dutta K, Patel P, Julien J-P. Protective effects of Withania somnifera extract in SOD1G93A mouse model of amyotrophic lateral sclerosis. Exp Neurol. 2018;309:193–204. Available from: https://www.sciencedirect.com/science/article/pii/S0014488618303546?via%3Dihub.
   Google Scholar
• Naidu PS, Singh A, Kulkarni SK. Effect of Withania somnifera root extract on haloperidol-induced orofacial dyskinesia: possible mechanisms of action. J Med Food. 2003;6(2):107–114.
   Google Scholar
• Naidu PS, Singh A, Kulkarni SK. Effect of Withania somnifera root extract on reserpine-induced orofacial dyskinesia and cognitive dysfunction. Phytother Res. 2006;20(2):140–146.
   Google Scholar
• Govindarajan R, Vijayakumar M, Pushpangadan P. Antioxidant approach to disease management and the role of ‘Rasayana’ herbs of Ayurveda. J Ethnopharmacol. 2005;99(2):165–178.
   Google Scholar
• Bhattacharya A, Ghosal S, Bhattacharya SK. 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. 2001;74(1):1–6.
   Google Scholar
• Kaur P, Sharma M, Mathur S, et al. Effect of 1-Oxo-5 β, 6 β -Epoxy-Witha-2-Ene-27-ethoxy-olide isolated from the roots of withania somnifera on stress indices in Wistar rats. J Altern Complement Med. 2003;9(6):897–907.
   Google Scholar
• Kumar P, Kumar A. 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. 2009;12(3):591–600.
   Google Scholar
• Parihar MS, Hemnani T. Phenolic antioxidants attenuate hippocampal neuronal cell damage against kainic acid induced excitotoxicity.J Biosci. 2003;28(1):121–128.
   Google Scholar
• Balkrishna A, Solleti SK, Singh H, et al. Withanolides from Withania somnifera ameliorate neutrophil infiltration in endotoxin-induced peritonitis by regulating oxidative stress and inflammatory cytokines. Planta Med. 2022;88(6):466–478.
   Google Scholar
• Khalil HMA, Eliwa HA, El-Shiekh RA, et al. Ashwagandha (Withania somnifera) root extract attenuates hepatic and cognitive deficits in thioacetamide-induced rat model of hepatic encephalopathy via induction of Nrf2/HO-1 and mitigation of NF-kB/MAPK signaling pathways. J Ethnopharmacol. 2021;277:114141.
   Google Scholar
• Mary NK, Babu BH, Padikkala J. Antiatherogenic effect of Caps HT2, an herbal Ayurvedic medicine formulation. Phytomedicine. 2003;10(6–7):474–482.
   Google Scholar
• Gupta SK, Mohanty I, Talwar KK, et al. Cardioprotection from ischemia and reperfusion injury by Withania somnifera: a hemodynamic, biochemical and histopathological assessment. Mol Cell Biochem. 2004;260(1):39–47.
   Google Scholar
• Venkatachalapathy D, Shivamallu C, Prasad SK, et al. Assessment of chemopreventive potential of the plant extracts against liver cancer using HepG2 cell line. Molecules. 2021;26(15):4593.
   Google Scholar
• Kumar R, Nayak D, Somasekharan SP. SILAC-based quantitative MS approach reveals Withaferin A regulated proteins in prostate cancer. J Proteomics. 2021;247:104334. Available from: https://www.sciencedirect.com/science/article/abs/pii/S1874391921002335?via%3Dihub.
   Google Scholar
• Sajida PA, Prabhu A. Anti-angiogenic, apoptotic and matrix metalloproteinase inhibitory activity of Withania somnifera (ashwagandha) on lung adenocarcinoma cells. Phytomedicine. 2021;90:153639. Available from: https://www.sciencedirect.com/science/article/abs/pii/S0944711321001823?via%3Dihub.
   Google Scholar
• Tomita T, Wadhwa R, Kaul SC, et al. Withanolide derivative 2,3-dihydro-3β-methoxy Withaferin-A modulates the circadian clock via interaction with RAR-related orphan receptor α (RORa). J Nat Prod. 2021;84(7):1882–1888.
   Google Scholar
• Kasture S, Vinci S, Ibba F, et al. Withania somnifera prevents morphine withdrawal-induced decrease in spine density in nucleus accumbens shell of rats: a confocal laser scanning microscopy study. Neurotox Res. 2009;16(4):343–355.
   Google Scholar
• Kulkarni SK, Ninan I. Inhibition of morphine tolerance and dependence by Withania somnifera in mice. J Ethnopharmacol. 1997;57(3):213–217.
   Google Scholar
• Orru A, Marchese G, Casu G, et al. Withania somnifera root extract prolongs analgesia and suppresses hyperalgesia in mice treated with morphine. Phytomedicine. 2014;21(5):745–752.
   Google Scholar
• Sharma L, Sharma A, Dash AK, et al. A standardized polyherbal preparation POL-6 diminishes alcohol withdrawal anxiety by regulating Gabra1, Gabra2, Gabra3, Gabra4, Gabra5 gene expression of GABAA receptor signaling pathway in rats. BMC Compl Med Ther. 2021;21(1):13. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789136/
   Google Scholar
• Jahanbakhsh SP, Manteghi AA, Emami SA, et al. Evaluation of the efficacy of Withania somnifera (Ashwagandha) root extract in patients with obsessive-compulsive disorder: a randomized double-blind placebo-controlled trial. Complement Ther Med. 2016;27:25–29.
   Google Scholar
• Fuladi S, Emami SA, Mohammadpour AH, et al. Assessment of Withania somnifera root extract efficacy in patients with generalized anxiety disorder: a randomized double-blind placebo-controlled trial. Curr Clin Pharmacol. 2021;16(2):191–196. Available from: https://www.eurekaselect.com/180848/article
   Google Scholar
• Lopresti AL, Smith SJ, Malvi H, et al. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract. Medicine (Baltimore). 2019;98(37):e17186.
   Google Scholar
• Cooley K, Szczurko O, Perri D, et al. Naturopathic care for anxiety: a randomized controlled trial ISRCTN78958974. PLoS One. 2009;4(8):e6628.
   Google Scholar
• Choudhary D, Bhattacharyya S, Joshi K. Body weight management in adults under chronic stress through treatment with ashwagandha root extract. J Evid Based Complementary Altern Med. 2017;22(1):96–106.
   Google Scholar
• Chengappa KNR, Brar JS, Gannon JM, et al.Adjunctive use of a standardized extract of Withania somnifera (Ashwagandha) to treat symptom exacerbation in schizophrenia: a randomized, double-blind, placebo-controlled study. J Clin Psychiatry. 2018;79(5):17m11826.
   Google Scholar
• Gannon JM, Brar J, Rai A, et al. Effects of a standardized extract of Withania somnifera (Ashwagandha) on depression and anxiety symptoms in persons with schizophrenia participating in a randomized, placebo-controlled clinical trial. Ann Clin Psychiatry. 2019;31(2):123–129. Available from: https://www.aacp.com/article/buy_now/?id=581
   Google Scholar
• Agnihotri AP, Sontakke SD, Thawani VR, et al. Effects of Withania somnifera in patients of schizophrenia: a randomized, double blind, placebo controlled pilot trial study. Indian J Pharmacol. 2013;45(4):417–418. Available from: https://www.ijp-online.com/text.asp?2013/45/4/417/115012
   Google Scholar
• Choudhary D, Bhattacharyya S, Bose S. Efficacy and safety of Ashwagandha (Withania somnifera (L.) Dunal) root extract in improving memory and cognitive functions. J Dietary Supplements. 2017;14(6):599–612.
   Google Scholar
• Pingali U, Pilli R, Fatima N. Effect of standardized aqueous extract of Withania somnifera on tests of cognitive and psychomotor performance in healthy human participants. Pharmacognosy Res. 2014;6(1):12–18.
   Google Scholar
• Hosseini N, Moharari F, Soltanifar A, et al. Evaluation of the effectiveness of withania somnifera root extract on the anxiety symptoms among children with ADHD in Mashhad. Pak J Med Health Sci. 2019;13(1):210–216. Available from: https://www.pjmhsonline.com/2019/jan_march/pdf/210.pdf
   Google Scholar
• Langade D, Thakare V, Kanchi S, et al. Clinical evaluation of the pharmacological impact of ashwagandha root extract on sleep in healthy volunteers and insomnia patients: a double-blind, randomized, parallel-group, placebo-controlled study. J Ethnopharmacol. 2021;264:113276.
   Google Scholar
• Deshpande A, Irani N, Balkrishnan R, et al. A randomized, double blind, placebo controlled study to evaluate the effects of ashwagandha (Withania somnifera) extract on sleep quality in healthy adults. Sleep Med. 2020;72:28–36.
   Google Scholar
• Lopresti AL, Drummond PD, Smith SJ. A randomized, double-blind, placebo-controlled, crossover study examining the hormonal and vitality effects of ashwagandha (Withania somnifera) in aging, overweight males. Am J Mens Health. 2019;13(2):1557988319835985.
   Google Scholar
• Dongre S, Langade D, Bhattacharyya S. Efficacy and safety of Ashwagandha (Withania somnifera) root extract in improving sexual function in women: a pilot study. Biomed Res Int. 2015;2015:284154. DOI:10.1155/2015/284154.
   Google Scholar
• Tiwari S, Gupta SK, Pathak AK. A double-blind, randomized, placebo-controlled trial on the effect of Ashwagandha (Withania somnifera dunal.) root extract in improving cardiorespiratory endurance and recovery in healthy athletic adults. J Ethnopharmacol. 2021;272:113929.
   Google Scholar
• Wankhede S, Langade D, Joshi K, et al. Examining the effect of Withania somnifera supplementation on muscle strength and recovery: a randomized controlled trial. J Int Soc Sports Nutr. 2015;12(1):43.
   Google Scholar
• Ziegenfuss TN, Kedia AW, Sandrock JE, et al. Effects of an aqueous extract of Withania somnifera on strength training adaptations and recovery: the STAR Trial. Nutrients. 2018;10(11):1807.
   Google Scholar
• Pérez-Gómez J, Villafaina S, Adsuar JC, et al. Effects of Ashwagandha (Withania somnifera) on VO2max: a systematic review and meta-analysis. Nutrients. 2020;12(4):1119.
   Google Scholar
• Rahman T, Hasan MR, Choudhuri MSK. Effect of Ashwagandharista (Withania somnifera) on the kidney functions of male and female rats. Jahangirnagar Uni J Bio Sci. 2019;8(1):1–7. Available from: https://www.banglajol.info/index.php/JUJBS/article/view/42462
   Google Scholar
• Ishtiaq S, Akram M, Kamran SH, et al. Acute and sub-acute toxicity study of a Pakistani polyherbal formulation. BMC Complement Altern Med. 2017;17(1):387. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5545041/
   Google Scholar
• Padmavathi B, Rath PC, Rao AR, et al. Roots of Withania somnifera inhibit forestomach and skin carcinogenesis in mice. Evid Based Complement Alternat Med. 2005;2(1):99–105.
   Google Scholar
• Siddiqui S, Ahmed N, Goswami M, et al. DNA damage by Withanone as a potential cause of liver toxicity observed for herbal products of Withania somnifera (Ashwagandha). Curr Res Toxicol. 2021;2:72–81. Available from: https://www.sciencedirect.com/science/article/pii/S2666027X21000074?via%3Dihub
   Google Scholar
• Ilayperuma I, Ratnasooriya WD, Weerasooriya TR. Effect of Withania somnifera root extract on the sexual behaviour of male rats. Asian J Androl. 2002;4(4):295–298. Available from: http://www.asiaandro.com/Abstract.asp?id=1012
   Google Scholar
• Abdel-Magied EM, Abdel-Rahman HA, Harraz FM. The effect of aqueous extracts of Cynomorium coccineum and Withania somnifera on testicular development in immature Wistar rats. J Ethnopharmacol. 2001;75(1):1–4.
   Google Scholar
• Al-Qarawi AA, Abdel-Rahman HA, El-Badry AA, et al. The effect of extracts of Cynomorium coccineum and Withania somnifera on gonadotrophins and ovarian follicles of immature Wistar rats. Phytother Res. 2000;14(4):288–290.
   Google Scholar
• National Institute of Diabetes and Digestive and Kidney Diseases. Ashwagandha. In: LiverTox: clinical and research information on drug-induced liver injury, Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012. p.1–4. Available from: http://www.ncbi.nlm.nih.gov/books/NBK548536/
   Google Scholar
• van der Hooft CS, Hoekstra A, Winter A, et al. [Thyrotoxicosis following the use of ashwagandha.] . Ned Tijdschr Geneeskd. 2005;149(149):2637–2638. Available from: https://pubmed.ncbi.nlm.nih.gov/16355578/
   Google Scholar
• Gannon JM, Forrest PE, Roy Chengappa KN. Subtle changes in thyroid indices during a placebo-controlled study of an extract of Withania somnifera in persons with bipolar disorder.J Ayurveda Integr Med. 2014;5(4):241–245.
   Google Scholar
• Panda S, Kar A. Changes in thyroid hormone concentrations after administration of ashwagandha root extract to adult male mice. J Pharm Pharmacol. 1998;50(9):1065–1068.
   Google Scholar
• Panda S, Kar A. Withania somnifera and Bauhinia purpurea in the regulation of circulating thyroid hormone concentrations in female mice. J Ethnopharmacol. 1999;67(2):233–239.
   Google Scholar
• Andrade C. Electroconvulsive therapy: methods and results of basic science research at NIMHANS. In: Khanna S, Channabasavanna SM, Keshavan MS, editors. Methods in biological psychiatry research. New Delhi: Tata McGraw-Hill; 1995. p. 114–138.
   Google Scholar
• Andrade C, Sudha S, Venkataraman BV. Herbal treatments for ECS-induced memory deficits: a review of research and a discussion on animal models. J ECT. 2000;16(2):144–156.
   Google Scholar
• Andrade C. Signal-to-noise ratio, variability, and their relevance in clinical trials. J Clin Psychiatry. 2013;74(5):19584.
   Google Scholar
• Andrade C. Anti-inflammatory strategies in the treatment of schizophrenia.Expert Rev Clin Pharmacol. 2016;9(2):161–163.
   Google Scholar
• Andrade C, Aswath A, Chaturvedi SK, et al. A double-blind, placebo-controlled evaluation of the anxiolytic efficacy of an ethanolic extract of Withania somnifera. Indian J Psychiatry. 2000;42(3):295–301. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2958355/
   Google Scholar
• Andrade C, Rao NS. How antidepressant drugs act: a primer on neuroplasticity as the eventual mediator of antidepressant efficacy.Indian J Psychiatry. 2010;52(4):378–386.
   Google Scholar