Abstract
Different formulations of ashwagandha have been utilized for the treatment of neurological disorders. The present manuscript aimed to discuss various roles of Withania somnifera, (ashwagandha) in the treatment of neurological disorders. In the literature, several neuroprotective phytoconstituents of ashwagandha have been reported, with important pharmacological effects on neurological and brain disorders such as anxiety, Alzheimer's, Parkinson's, and Schizophrenia. Preclinical studies, clinical trials, and patents indicate that Withania somnifera has a wide range of potential as a neuroprotective in several neurological disorders. After a complete literature survey, it can be concluded that Withania somnifera has significant potential to treat neurological disorders.
Keywords: Pharmacological activity, phytoconstituent, Withania somnifera, Ashwagandha, neurological disorder, herbal drug.
[1]
Singh N, Bhalla M, de Jager P, Gilca M. An overview on Ashwagandha: A Rasayana (rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med 2011; 8(5) (Suppl.): 208-13.
[http://dx.doi.org/10.4314/ajtcam.v8i5S.9] [PMID: 22754076]
[http://dx.doi.org/10.4314/ajtcam.v8i5S.9] [PMID: 22754076]
[2]
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): 12-8.
[http://dx.doi.org/10.4103/0974-8490.122912] [PMID: 24497737]
[http://dx.doi.org/10.4103/0974-8490.122912] [PMID: 24497737]
[3]
Ahmed ME, Javed H, Khan MM, et al. Attenuation of oxidative damage-associated cognitive decline by Withania somnifera in rat model of streptozotocin-induced cognitive impairment. Protoplasma 2013; 250(5): 1067-78.
[http://dx.doi.org/10.1007/s00709-013-0482-2] [PMID: 23340606]
[http://dx.doi.org/10.1007/s00709-013-0482-2] [PMID: 23340606]
[4]
Rastogi RP, Mehrotra BN. Compendium of indian medicinal plants. New Delhi: 2nd Reprint, central drug research institute, lucknow and national institute of science communication, council of scientific and industrial research 1998.
[5]
Ganzera M, Choudhary MI, Khan IA. Quantitative HPLC analysis of withanolides in Withania somnifera. Fitoterapia 2003; 74(1-2): 68-76.
[http://dx.doi.org/10.1016/S0367-326X(02)00325-8] [PMID: 12628397]
[http://dx.doi.org/10.1016/S0367-326X(02)00325-8] [PMID: 12628397]
[6]
Gupta GL, Rana AC. Withania somnifera (Ashwagandha): A review. Pharmacogn Rev 2007; 1(1): 129-36.
[7]
Ghosal S, Lal J, Srivastava R, et al. Immunomodulatory and CNS effects of Sitoindosides IX and X, Two new Glycowithanolides from Withania somnifera’. Phytother Res 1899; 3(5): 201-6.
[http://dx.doi.org/10.1002/ptr.2650030510]
[http://dx.doi.org/10.1002/ptr.2650030510]
[8]
Warrier PK, Nambiar VPK, Ramankutty C. Indian medicinal plants a compendium of 500 species. New Delhi: Orient Longman Pvt. Ltd. 1995; pp. 409-10.
[9]
Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (Ashwagandha): A review. Altern Med Rev 2000; 5(4): 334-46.
[PMID: 10956379]
[PMID: 10956379]
[10]
Bhattacharya SK, Goel RK, Kaur R, Ghosal S. Anti - stress activity of Sitoindosides VII and VIII. New Acylsterylglucosides from Withania somnifera. Phytother Res 1987; 1(1): 32-7.
[http://dx.doi.org/10.1002/ptr.2650010108]
[http://dx.doi.org/10.1002/ptr.2650010108]
[11]
Ghosal S, Srivastava RS, Bhattacharya SK, Upadhyay SN, Jaiswal AK, Chattopadhyay U. Immunomodulatory and CNS effects of sitoindosides IX and X, two new glycowithanolides form Withania somnifera’. Phytother Res 1989; 2(5): 201-6.
[http://dx.doi.org/10.1002/ptr.2650030510]
[http://dx.doi.org/10.1002/ptr.2650030510]
[12]
Atta-ur-Rahma. Samina-Abbas, Dur-e-Shahwar, Jamal SA, Choudhary MI, Abbas S. New withanolides from Withania spp. J Nat Prod 1991; 56: 1000-6.
[13]
Singh N. Effect of Withania somnifera and Panax ginseng on dopaminergic receptors in rat brain during stress. Planta Med 55(1): 95.
[14]
Singh N, Misra N. Experimental methods tools for assessment of anti-stress activity in medicinal plants. J Biomed Res 1993; 12(182): 124-7.
[15]
Singh N. A pharmaco-clinical evaluation of some Ayurvedic crude plant drugs as anti-stress agents and their usefulness in some stress diseases of man. Ann Nat Acad Ind Med 1986; 2(1): 14-26.
[16]
Nagashyana N, Sankarankutty P, Nampoothiri MRV, Moahan P, Mohan Kumar P. Association of L- dopa with recovery following Ayurvedic medication in Parkinson’s disease. J Neurol Sci 2000; 176: 1121-7.
[17]
Bhattacharya SK, Kumar A, Ghosal S. Effects of glycowithanolides from Withania somnifera on animal model of Alzheimer’s disease and perturbed central cholinergic markers of cognition in rats. Phytother Res 1995; 9(2): 110-3.
[http://dx.doi.org/10.1002/ptr.2650090206]
[http://dx.doi.org/10.1002/ptr.2650090206]
[18]
Sharma GS. Ashwagandha rishta- rastantra sar evam sidhyaprayog sangrah. Nagpur: Department of Ayurveda, Krishna Gopal Ayurveda Bhawan 1938; pp. 743-4.
[19]
Singh N. Dilemma of ayurvedic herbal medicines/food supplements proc workshop on essential medicines, adverse drug reactions and therapeutic drug monitoring. Lucknow: Dept. of Pharmacology & Therapeutics, KGMU, Scientific Convention Centre 2005; p. 35.41.
[20]
Singh N. Ayurvedo-herbal medicines - the need of the time - herbal drugs, a twenty first century perspective. Delhi: Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization (DRDO), Govt. of India 2006; pp. 535-47.
[21]
Shree P, Mishra P, Selvaraj C, et al. Targeting COVID-19 (SARS-CoV-2) main protease through active phytochemicals of ayurvedic medicinal plants - Withania somnifera “(Ashwagandha), Tinospora cordifolia (Giloy) and Ocimum sanctum (Tulsi) - a molecular docking study.”. J Biomol Struct Dyn 2022; 40(1): 190-203.
[http://dx.doi.org/10.1080/07391102.2020.1810778] [PMID: 32851919]
[http://dx.doi.org/10.1080/07391102.2020.1810778] [PMID: 32851919]
[22]
Dharmendra M, Deepak S. Evaluation of traditional ayurvedic preparation for prevention and management of the novel coronavirus (SARS-CoV-2) using molecular docking approach. ChemRxiv 2020.
[http://dx.doi.org/10.26434/chemrxiv.12110214.v1]
[http://dx.doi.org/10.26434/chemrxiv.12110214.v1]
[23]
Balkrishna A, Pokhrel S, Singh J, Varshney A. Withanone from Withania somnifera may inhibit novel coronavirus (COVID-19) entry by disrupting interactions between viral S-protein receptor binding domain and host ACE2 receptor. Virol J 2020.
[http://dx.doi.org/10.21203/rs.3.rs-17806/v1]
[http://dx.doi.org/10.21203/rs.3.rs-17806/v1]
[24]
Manchanda S, Mishra R, Singh R, Kaur T, Kaur G. Aqueous leaf extract of Withania somnifera as a potential neuroprotective agent in sleep-deprived rats: A mechanistic study. Mol Neurobiol 2017; 54(4): 3050-61.
[http://dx.doi.org/10.1007/s12035-016-9883-5] [PMID: 27037574]
[http://dx.doi.org/10.1007/s12035-016-9883-5] [PMID: 27037574]
[25]
Ahmad M, Dar NJ. 8 - Withania somnifera: Ethnobotany, pharmacology, and therapeutic functions. In: Bagchi D, Ed. Sustained energy for enhanced human functions and activity. 137- 54.Cambridge, Massachusetts: Academic Press 2017; pp.
[26]
Kuboyama T, Tohda C, Komatsu K. Effects of Ashwagandha (roots of Withania somnifera) on neurodegenerative diseases. Biol Pharm Bull 2014; 37(6): 892-7.
[http://dx.doi.org/10.1248/bpb.b14-00022] [PMID: 24882401]
[http://dx.doi.org/10.1248/bpb.b14-00022] [PMID: 24882401]
[27]
Baitharu I, Jain V, Deep SN, et al. Withania somnifera root extract ameliorates hypobaric hypoxia induced memory impairment in rats. J Ethnopharmacol 2013; 145(2): 431-41.
[http://dx.doi.org/10.1016/j.jep.2012.10.063] [PMID: 23211660]
[http://dx.doi.org/10.1016/j.jep.2012.10.063] [PMID: 23211660]
[28]
Chandrasekhar K, Kapoor J, Anishetty S. 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 2012; 34(3): 255-62.
[http://dx.doi.org/10.4103/0253-7176.106022] [PMID: 23439798]
[http://dx.doi.org/10.4103/0253-7176.106022] [PMID: 23439798]
[29]
Khyati SS, Anup BT. A randomized double blind placebo controlled study of Ashwagandha on generalized anxiety disorder. Int Ayurvedic Med J 2013; 1: 1-7.
[30]
Pratte MA, Nanavati KB, Young V, Morley CP. An alternative treatment for anxiety: A systematic review of human trial results reported for the Ayurvedic herb ashwagandha (Withania somnifera). J Altern Complement Med 2014; 20(12): 901-8.
[http://dx.doi.org/10.1089/acm.2014.0177] [PMID: 25405876]
[http://dx.doi.org/10.1089/acm.2014.0177] [PMID: 25405876]
[31]
Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S. Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: An experimental study. Phytomedicine 2000; 7(6): 463-9.
[http://dx.doi.org/10.1016/S0944-7113(00)80030-6] [PMID: 11194174]
[http://dx.doi.org/10.1016/S0944-7113(00)80030-6] [PMID: 11194174]
[32]
Gajbhiye NA, Makasana J, Kumar S. Accumulation of three important bioactive compounds in different plant parts of Withania somnifera and its determination by the LC-ESI-MS-MS (MRM) method. Method J Chromatogr Sci 2015; 53(10): 1749-56.
[http://dx.doi.org/10.1093/chromsci/bmv088] [PMID: 26153381]
[http://dx.doi.org/10.1093/chromsci/bmv088] [PMID: 26153381]
[33]
Mirjalili MH, Moyano E, Bonfill M, Cusido RM, Palazón J. Steroidal lactones from Withania somnifera, an ancient plant for novel medicine. Molecules 2009; 14(7): 2373-93.
[http://dx.doi.org/10.3390/molecules14072373] [PMID: 19633611]
[http://dx.doi.org/10.3390/molecules14072373] [PMID: 19633611]
[34]
Wal P, Wal A. Chapter 34 - An overview of adaptogens with a special emphasis on Withania and Rhodiola. In: Bagchi D, Nair S, Sen CK, Eds. Nutrition and enhanced sports performance. Cambridge, Massachusetts: Academic Press 2013; pp. 343-50.
[35]
Syed AA, Reza MI, Singh P, Thombre GK, Gayen JR. Withania somnifera in neurological disorders: Ethnopharmacological evidence, mechanism of action and its progress in delivery systems. Curr Drug Metab 2021; 22(7): 561-71.
[http://dx.doi.org/10.2174/1389200222666210203182716] [PMID: 33538666]
[http://dx.doi.org/10.2174/1389200222666210203182716] [PMID: 33538666]
[36]
Dar NJ, Muzamil A. Neurodegenerative diseases and Withania somnifera (L.): An update. J Ethnopharmacol 2020; 256: 112769.
[http://dx.doi.org/10.1016/j.jep.2020.112769] [PMID: 32240781]
[http://dx.doi.org/10.1016/j.jep.2020.112769] [PMID: 32240781]
[37]
Zahiruddin S, Basist P, Parveen A, et al. Ashwagandha in brain disorders: A review of recent developments. J Ethnopharmacol 2020; 257: 112876.
[http://dx.doi.org/10.1016/j.jep.2020.112876] [PMID: 32305638]
[http://dx.doi.org/10.1016/j.jep.2020.112876] [PMID: 32305638]
[38]
Preeti Tiwari, Patel RK. Comparison of anti-hyperlipidemic activity in Ashwagandha rishta prepared by traditional and modern methods. Asian J Res Chem 2010; 3(3): 574.
[39]
Ali KM, Chatterjee K, De D, Maiti S, Pathak TK, et al. Evaluation of antioxidant activity of seed of Holarrhena antidysenterica: An approach through different in vitro models. J Nat Pharm 2011; 2(2): 115-8.
[http://dx.doi.org/10.4103/2229-5119.83964]
[http://dx.doi.org/10.4103/2229-5119.83964]
[40]
Bhattacharya PN, Jha DK. Antidermatophytic and antioxidant activity of Terminalia arjuna (roxb.) Wight &Arn. Bark. Int J Res Pharm Biol Arch 2011; 2: 973-9.
[41]
Narasimhan S, Govindarajan R, Vijayakumar M, Mehrotra S. Free radical scavenging potential of Chlorophytum tuberosum Baker. J Ethnopharmacol 2006; 104(3): 423-5.
[http://dx.doi.org/10.1016/j.jep.2005.09.029] [PMID: 16271837]
[http://dx.doi.org/10.1016/j.jep.2005.09.029] [PMID: 16271837]
[42]
Joharapurkar AA, Zambad SP, Wanjari MM, Umathe SN. In vivo evaluation of antioxidant activity of alcoholic extract of Rubia cordifolia Linn. and its influence on ethanol-induced immunosuppression. Ind J Pharmacol 2003; 35: 232-6.
[43]
Manwar J, Mahadik K, Sathiyanarayanan L, Paradkar A, Patil S. Comparative antioxidant potential of Withania somnifera based herbal formulation prepared by traditional and non-traditional fermentation processes. Integr Med Res 2013; 2(2): 56-61.
[http://dx.doi.org/10.1016/j.imr.2013.04.002] [PMID: 28664055]
[http://dx.doi.org/10.1016/j.imr.2013.04.002] [PMID: 28664055]
[44]
Chaurasiya ND, Uniyal GC, Lal P, et al. Analysis of withanolides in root and leaf of Withania somnifera by HPLC with photodiode array and evaporative light scattering detection. Phytochem Anal 2008; 19(2): 148-54.
[http://dx.doi.org/10.1002/pca.1029] [PMID: 17879227]
[http://dx.doi.org/10.1002/pca.1029] [PMID: 17879227]
[45]
Mundkinajeddu D, Sawant LP, Koshy R, et al. Development and validation of high performance liquid chromatography method for simultaneous estimation of flavonoid glycosides in Withania somnifera aerial parts. ISRN Anal Chem 2014; 2014: 1-6.
[http://dx.doi.org/10.1155/2014/351547]
[http://dx.doi.org/10.1155/2014/351547]
[46]
Sangwan RS, Chaurasiya ND, Misra LN, et al. Phytochemical variability in commercial herbal products and preparations of Withania somnifera (Ashwagandha). Curr Sci 2004; 86: 461-5.
[47]
Chatterjee S, Srivastava S, Khalid A, et al. Comprehensive metabolic fingerprinting of Withania somnifera leaf and root extracts. Phytochemistry 2010; 71(10): 1085-94.
[http://dx.doi.org/10.1016/j.phytochem.2010.04.001] [PMID: 20483437]
[http://dx.doi.org/10.1016/j.phytochem.2010.04.001] [PMID: 20483437]
[48]
Elango S. Estimation of alkaloid content of Ashwagandha (Withania somnifera) with HPLC methods. J Exp Sci 2011; 2: 39-41.
[49]
Devkar S, Badhe Y, Jagtap S, Hegde M. Quantification of major bioactive withanolides in Withania somnifera (Ashwagandha) roots by HPTLC for rapid validation of Ayurvedic products. J Planar Chromatogr Mod TLC 2012; 25(4): 290-4.
[http://dx.doi.org/10.1556/JPC.25.2012.4.2]
[http://dx.doi.org/10.1556/JPC.25.2012.4.2]
[50]
Nile SH, Park SW. HPTLC densitometry method for simultaneous determination of flavonoids in selected medicinal plants. Front Life Sci 2015; 8(1): 97-103.
[http://dx.doi.org/10.1080/21553769.2014.969387]
[http://dx.doi.org/10.1080/21553769.2014.969387]
[51]
Tomar V, Beuerle T, Sircar D. A validated HPTLC method for the simultaneous quantifications of three phenolic acids and three withanolides from Withania somnifera plants and its herbal products. J Chromatogr B Analyt Technol Biomed Life Sci 2019; 1124: 154-60.
[http://dx.doi.org/10.1016/j.jchromb.2019.06.009] [PMID: 31200247]
[http://dx.doi.org/10.1016/j.jchromb.2019.06.009] [PMID: 31200247]
[52]
Trivedi MK, Panda P, Sethi KK, Jana S. Metabolite profiling in Withania somnifera roots hydroalcoholic extract using LC/MS, GC/MS and NMR spectroscopy. Chem Biodivers 2017; 14(3): e1600280.
[http://dx.doi.org/10.1002/cbdv.201600280] [PMID: 27743505]
[http://dx.doi.org/10.1002/cbdv.201600280] [PMID: 27743505]
[53]
Chandra P, Kannujia R, Saxena A, et al. Quantitative determination of multi markers in five varieties of Withania somnifera using ultra-high performance liquid chromatography with hybrid triple quadrupole linear ion trap mass spectrometer combined with multivariate analysis: Application to pharmaceutical dosage forms. J Pharm Biomed Anal 2016; 129: 419-26.
[http://dx.doi.org/10.1016/j.jpba.2016.07.032] [PMID: 27475405]
[http://dx.doi.org/10.1016/j.jpba.2016.07.032] [PMID: 27475405]
[54]
Mirjalili MH, Navarro A, Hernandez L, Jáuregui O, Bonfill M. LC-MS/MS method for the quantification of withaferin-A in plant extracts of Withania spp. Acta Chromatogr 2013; 25(4): 745-54.
[http://dx.doi.org/10.1556/AChrom.25.2013.4.12]
[http://dx.doi.org/10.1556/AChrom.25.2013.4.12]
[55]
Manwar JV, Mahadik KR, Paradkar AR, Takle SP, Sathiyanarayanan L, Patil SV. Determination of withanolides from the roots and herbal formulation of Withania somnifera by HPLC using DAD and ELSD detector. Pharm Sin 2012; 3: 41-6.
[56]
Crowell EA, Ough CS. A modified procedure for alcohol determination by dichromate oxidation. Am J Enol Vitic 1979; 30: 61-3.
[57]
Lane JH. Determination of reducing sugars by means of Fehling’s solution with methylene blue as internal indicator. J Soc Chem Ind Trans 1923; 32T-36T 1923.
[58]
Manwar J, Mahadik K, Paradkar A, Patil S, Sathiyanarayanan L, Manmode R. Gas chromatography method for the determination of non-ethanol volatile compounds in herbal formulation. Int J Ana BioanalChem 2013; 1(3): 12-7.
[59]
Ristivojević P, Trifković J, Vovk I, Milojković-Opsenica D. Comparative study of different approaches for multivariate image analysis in HPTLC fingerprinting of natural products such as plant resin. Talanta 2017; 162: 72-9.
[http://dx.doi.org/10.1016/j.talanta.2016.10.023] [PMID: 27837887]
[http://dx.doi.org/10.1016/j.talanta.2016.10.023] [PMID: 27837887]
[60]
Olech M, Komsta Ł, Nowak R, Cieśla Ł, Waksmundzka-Hajnos M. Investigation of antiradical activity of plant material by thin-layer chromatography with image processing. Food Chem 2012; 132(1): 549-53.
[http://dx.doi.org/10.1016/j.foodchem.2011.10.067] [PMID: 26434330]
[http://dx.doi.org/10.1016/j.foodchem.2011.10.067] [PMID: 26434330]
[61]
Alaerts G, Dejaegher B, Smeyers-Verbeke J, Vander Heyden Y. Recent developments in chromatographic fingerprints from herbal products: Set-up and data analysis. Comb Chem High Throughput Screen 2010; 13(10): 900-22.
[http://dx.doi.org/10.2174/138620710793360284] [PMID: 20883186]
[http://dx.doi.org/10.2174/138620710793360284] [PMID: 20883186]
[62]
Bhargavi S, Madhan Shankar SR. Dual herbal combination of Withania somnifera and five Rasayana herbs: A phytochemical, antioxidant, and chemometric profiling. J Ayurveda Integr Med 2021; 12(2): 283-93.
[63]
Aboli G, Ganesh S, Sandeep P, et al. Investigating 11 withanosides and withanolides by UHPLC–PDA and mass fragmentation studies from Ashwagandha (Withania somnifera). ACS Omega 2020; 5(43): 27933-43.
[PMID: 33163776]
[PMID: 33163776]
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