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Cellmed Orthocellular Medicine and Pharmaceutical Association (셀메드 세포교정의약학회)
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Chemistry and pharmacology of withania somnifera: An update

  • Kumar, Vikas (Neuropharmacology Research Laboratory, Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University)) ;
  • Dey, Amitabha (Neuropharmacology Research Laboratory, Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University)) ;
  • Hadimani, Mallinath B. (Department of Chemistry, Graduate School of Arts and Sciences, Wake Forest University) ;
  • Marcovic, Tatjana (Institute of Medicinal Plant Research "Dr Josif Pancic" Belgrade) ;
  • Emerald, Mila (Phytoceuticals International)
  • Received : 2014.10.05
  • Accepted : 2015.02.24
  • Published : 2015.02.28
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Abstract

Withania somnifera (Ashwagandha) is an important Rasayana herb and widely considered as Indian ginseng in Ayurveda. In traditional system of Indian medicine, it is used as tonic to rejuvenate the body and increase longevity. In Ayurvedic preparations, various parts of the plant have been used to treat variety of ailments that affect the human health. However, dried roots of the plant are widely used for the treatment of nervous and sexual disorders. The major active chemical constituents of this plant are withanolides, which is responsible for its wide range of biological activities. Since the beginning of the $20^{th}$ century, a significant amount of research has been done and efforts are ongoing to further explore other bioactive constituents, and many pharmacological studies have been carried out to describe their disease preventing mechanisms. In this chapter, we have reviewed the chemistry and pharmacological basis of W. somnifera in various human ailments.

Keywords

References

  1. Ahmad MK, Mahdi AA, Shukla KK, Islam N, Rajender S, Madhukar D, Shankhwar SN, Ahmad S. Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males. Fertil Steril. 2010;94:989-996 https://doi.org/10.1016/j.fertnstert.2009.04.046
  2. Alam N, Hossain M, Mottalib Md A, Sulaiman SA, Gan SH, Khalil Md I. Methanolic extracts of Withania somnifera leaves, fruits and roots possess antioxidant properties and antibacterial activities. BMC Complement Altern Med. 2012;12:175. https://doi.org/10.1186/1472-6882-12-175
  3. Al-Ani N, Hadi SA, Nazar R. Antimicrobial activities of Withania somnifera Crude extract. Sci Agri. 2013;4:74-76.
  4. Amaravathi P, Srilatha C, Ramadevi V, Sujatha K. Immunomodulatory effect of Withania somnifera (ashwagandha) against fenvalerate induced immunotoxicity. Int J Pharm Biol Sci. 2012;3:B10-B16.
  5. Ambiye VR, Langade D, dongre S, aptikar P, Kulkarni M, Dongre A. Clinical Evaluation of the Spermatogenic Activity of the Root Extract of Ashwagandha (Withania somnifera) in Oligospermic Males: A Pilot Study. Evid Based Complement Alternat Med. 2013;2013:571420.
  6. Anwer T, Sharma M, Pillai KK, Iqbal M. Effect of Withania somnifera on insulin sensitivity in non-insulin-dependent diabetes mellitus rats. Basic Clin Pharmacol Toxicol. 2008;102:498-503. https://doi.org/10.1111/j.1742-7843.2008.00223.x
  7. Baitharu I, Jain V, Deep SN, Hota KB, Hota SK, Prasad D, Ilavazhagan G. Withania somnifera root extract ameliorates hypobaric hypoxia induced memory impairment in rats. J Ethnopharmacol. 2013;145:431-441. https://doi.org/10.1016/j.jep.2012.10.063
  8. Bhatnagar M, Sharma D, Salvi M. Neuroprotective Effects of Withania somnifera Dunal.: A Possible Mechanism. Neurochem Res. 2009;34:1975-1983. https://doi.org/10.1007/s11064-009-9987-7
  9. Bhattacharya SK, Bhattacharya A, Sairam K., Ghosal S. Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. Phytomedicine. 2000;7:463-469. https://doi.org/10.1016/S0944-7113(00)80030-6
  10. Bhattacharya SK, Muruganandam AV. Adaptogenic activity of Withania somnifera: An experimental study using a rat model of chronic stress. Pharmacol Biochem Behav. 2003;75:547-555. https://doi.org/10.1016/S0091-3057(03)00110-2
  11. Bone K. Clinical Applications of Ayurvedic and Chinese Herbs: Monographs for the Western Herbal Practitioner. (Warwick, Australia: Phytotherapy Press), 1996.
  12. Choudhary MI, Yousuf S, Rahman AU. Withanolides: Chemistry and Antitumor Activity. In Natural Products. Ramawat KG, Merillon JM ed. (Berlin, Heidelberg: Springer-Verlag), pp.3465-3495, 2013.
  13. Devi PU, Sharada AC, Solomon FE, Kamath MS. In vivo growth inhibitory effect of Withania somnifera (Ashwagandha) on a transplantable mouse tumor Sarcoma 180. Ind J Exp Biol. 1992;30:169-172.
  14. Elsakka M, Grigorescu E, Stanescu U, Stanescu U, Dorneanu V. New data referring to chemistry of Withania somnifera species. Rev Med Chir Soc Med Nat Iasi. 1990;94:385-387.
  15. Gardner Z, McGuffin M. American Herbal Products Association's Botanical Safety Hand Book. (Florida, United States: CRC Press, Taylor & Francis Group), 2013.
  16. Girdhari LG, Avtar CR. Synergistic effect of Withania somnifera dunal and L-dopa in the inhiition of haloperidol-induced catalepsy in mice. Phcog Mag. 2009;19:46-50.
  17. Grover A, Shandilya A, Agrawal V, Bisaria VS, Sundar D. Computational evidence to inhibition of human acetyl cholinesterase by withanolide A for Alzheimer treatment. J Biomol Struct Dyn. 2012;29:651-662. https://doi.org/10.1080/07391102.2012.10507408
  18. Gupta A, Mahdi AA, Shukla KK, Ahmad MK, Bansal N, Sankhwar P, Sankhwar SN. Efficacy of Withania simnifera on seminal plasma metabolites of infertile males: a proton NMR study at 800 MHz. J Ethnopharmacol. 2013;149:208-214. https://doi.org/10.1016/j.jep.2013.06.024
  19. Gupta A, Singh S. Evaluation of anti-inflammatory effect of Withania somnifera root on collaten-induced arthritis in rats. Pharm Biol. 2014;52:308-320. https://doi.org/10.3109/13880209.2013.835325
  20. Hahm ER, Moura MB, Kelley EE, Houten BV, Shiva S, Singh SV. Withaferin-A-induced apoptosis in human breast cancer cells is mediated by reactive oxyge species. PLoS One. 2011;6:e23354. https://doi.org/10.1371/journal.pone.0023354
  21. Hahm ER, Singh SV, Withaferin-A-induced apoptosis in human breast cancer cells is associated with suppression of inhibitor of apoptosis family protein expression. Cancer Lett. 2013;334:101-108. https://doi.org/10.1016/j.canlet.2012.08.026
  22. Hepper FN. Old World Withania (Solanaceae): A taxonomic review and key to the species. In Solanaceae III: Taxonomy, Chemistry, Evolution. In Kew Bulletin. Hawkes, Lester, Nee, Estrada eds. (London, English: Royal Botanic Gardens Kew and Linnean Society), pp.785-788, 1991.
  23. Hina S, Rehman KU, Dogar ZUH, Jahan N, Hameed M, Khan ZI, Ahmad K, Mukhtar K, Valeem E. Cardioprotective effect of gemmotherapeutically treated Withania somnifera against chemically induced myocardial injury. Pak J Bot. 2010;42:1487-1499.
  24. Hosny MH, Farouk HH. Protective effect of Withania somnifera against radiation-induced hepatotoxicity in rats. Ecotoxicol Environ Saf. 2012;80:14-19. https://doi.org/10.1016/j.ecoenv.2012.02.003
  25. Ilayperuma I, Ratnasooriya WD, Weerasooriya TR. Effect of Withania somnifera root extract on the sexual behaviour of male rats. Asian J Androl. 2002;4:295-298.
  26. Jayanthi MK, Prathima C, Huralikuppi JC, Suresha RN, Dhar M. Anti-depressant effects of Withania somnifera fat (Ashwagandha ghrutha) extract in experimental mice. Int J Pharm Bio Sci. 2012;3:33.
  27. Joshi P, Misra L, Siddique AA, Srivastava, Kunar S, Darokar MP. Epoxide group relationship with cytotoxicity in withanolide derivatives from Withania somnifera. Steroids. 2014;79:19-27. https://doi.org/10.1016/j.steroids.2013.10.008
  28. Kapoor S. Withania somnifera and its emerging anti-neoplastic effects. Inflammopharmacology. 2014;22:67. https://doi.org/10.1007/s10787-012-0162-4
  29. Kataria H, Shah N, Kaul SC, Wadhwa R, Kaur G. Water Extract of Ashwagandha Leaves Limits Proliferation and Migration, and Induces Differentiation in Glioma Cells. Evid Based Complement Alternat Med. 2011;2011:267614.
  30. Kataria H, Wadhwa R, Kaul SC, Kaur G. Water Extract from the Leaves of Withania somnifera Protect RA Differentiated C6 and IMR-32 Cells against Glutamate-Induced Excitotoxicity. PLoS One. 2012;7:e37080. https://doi.org/10.1371/journal.pone.0037080
  31. Khalili M. The Effect of Oral Adminisration of Withania somnifera Root on Formalin-Induced Pain in Diabetic Rats. Basic Clin Neurosci. 2009;1:29-31.
  32. Khan ZA, Ghosh AR. L-Arginine abolishes the anxiolytic-like effect of withaferin-A in the elevated plus-maze test in rats. Afr J Pharm Pharmacol. 2011;5:234-237. https://doi.org/10.5897/AJMR10.401
  33. Khedgikar V, Kushwaha P, Gautam J, Verma A, Changkija B, Kumar A, Sharma S, Nagar GK, Singh D, Trivedi PK, Sangwan NS, Mishra PR, Trivedi R. Withaferin A: a proteasomal inhibitor promotes healing after injury and exerts anabolic effect on osteoporotic bone. Cell Death Dis. 2013;4:e778. https://doi.org/10.1038/cddis.2013.294
  34. Koduru S, Kumar R, Srinivasan S, Evers MB, Damodaran C. Notch-1 inhibition by Withaferin-A: a therapeutic target against colon carcinogenesis. Mol Cancer Ther. 2010;9:202-210.
  35. Ku SK, Bae JS. Antiplatelet, anticoagulant, and profibrinolytic activities of withaferin-A. Vascul Pharmacol. 2014;60:120-126. https://doi.org/10.1016/j.vph.2014.01.009
  36. Ku SK, Han MS, Bae JS. Withaferin-A is an inhibitor of endothelial protein C receptor shedding in vitro and in vivo. Food Chem Toxicol. 2014;6:23-29.
  37. Kuboyama T, Tohda C, Komatsu K. Neuritic regeneration and synaptic reconstruction induced by withanolide A. Br J Pharmacol. 2005;144:961-971. https://doi.org/10.1038/sj.bjp.0706122
  38. 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;46:465-469.
  39. Kulkarni SK, Dhir A. Withania somnifera: An Indian ginseng. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32:1093-1105. https://doi.org/10.1016/j.pnpbp.2007.09.011
  40. Kurapati KRV, Atluri VSR, Samikkannu T, Nair MPN. Ashwagandha (Withania somnifera) Reverses ${\beta}$-Anyloid 1-42 Induced Toxicity in Human Neuronal Cells: Implications in HIV-Associated Neurocognitive Disorders (HAND). PLoS One. 2013;8:e77624. https://doi.org/10.1371/journal.pone.0077624
  41. Lavie D, Glotter E, Shvo Y. Constituents of Withania somnifera Dun III. The side chain of withaferin A. J Org Chem. 1965;30:1774-1778. https://doi.org/10.1021/jo01017a015
  42. Mabberley DJ. Mabberley's Plant-Book: a portable dictionary of plants, their classification and uses. (Cambridge, England: Cambridge University Press), 2008.
  43. Maity T, Adhikari A, Bhattacharya K, Biswas S, Debnath PK, Maharana CS. A study on evalution of antidepressant effect of Imipramine adjunct with Aswagandha and Bramhi. Nepal Med College J. 2011;13:250-253.
  44. Malik T, Pandey DK, Dogra N. Ameliorative Potential of Aqueous Root Extract of Withania somnifera Against Paracetamol Induced Liver Damage in Mice. Pharmacologia. 2013;4:89-94. https://doi.org/10.5567/pharmacologia.2013.89.94
  45. Manjunath M J, Muralidhara. 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. 2013;13:43-56. https://doi.org/10.2174/1871524911313010007
  46. Mirjalili MH, Moyano E, Bonfill M, Cusido RM, Palazon J. Steroidal Lactones from Withania somnifera, an Ancient Plant for Novel Medicine. Molecules. 2009;14:2373-2393. https://doi.org/10.3390/molecules14072373
  47. Mishra LC, Singh BB. Scientific Basis for the Therapeutic Use of Withania somnifera (Ashwagandha): A Review. Altern Med Rev. 2000;5:334-346.
  48. Mohanty I, Arya DS, Dinda A, Talwar KK, Joshi S, Gupta SK. Mechanisms of cardioprotective effect of Withania somnifera in experimentally induced myocardial infarction. Basic clin Pharmacol Toxicol. 2004;94:184-190.
  49. Motiwala HF, Bazzill J, Samadi A, Zhang H, Timmermann BN, Cohen MS, Aube J. Synthesis and Cytotoxicity of Semisynthetic Withalongolide A Analogues. ACS Med Chem Lett. 2013;4:1069-1073. https://doi.org/10.1021/ml400267q
  50. Mulabagal V, Subaraju GV, Rao CV, Sivaramakrishna C, DeWitt DL, Holnes D, Sung B, Aggarwal BB, Tsay HS, Nair MG. Withanolide Sulfoxide from Aswagandha Roots Inhibits Nuclear Transcription Factor-Kappa-B, Cyclooxygenase and Tumor Cell Proliferation. Phytother Res. 2009;22:987-992.
  51. Muralikrishnan G, Amanullah S, Basha MI, Dinda AK, Shakeel F. Modulating effect of Withania somnifera on TCA cycle enzymes and electron transport chain in azoxymethane-induced colon cancer in mice. Immunopharmacol Immunotoxicol. 2010a;32:523-527. https://doi.org/10.3109/08923970903581540
  52. Muralikrishnan G, Dinda AK, Shakeel F. Immunomodulatory effects of Withania somnifera on azoxymethane induced experimental colon cancer in mice. Immunol Invest. 2010b;39:688-698. https://doi.org/10.3109/08820139.2010.487083
  53. Mwitari PG, Ayeka PA, Ondicho J, Matu EN, Bii CC. Antimicrobial activity and probable mechanisms of action of medicinal plants of Kenya: Withania somnifera, Warbugia ugandensis, Prunus africana and Plectrunthus barbatus. PlosOne. 2013;8:e65619. https://doi.org/10.1371/journal.pone.0065619
  54. Nema R, Khare S, Jain P, Pradhan A. Anticancer activity of Withania somnifera (leaves) flavonoids compound. Int J Pharm Sci Rev Res. 2013;19:103-106.
  55. Oh JH, Kwon TK. Withaferin-A inhibits tumor necrosis factor alpha-induced expression of cell adhesion molecules by inactivation of Akt and NF-kappaB in human pulmonary epithelial cells. Int Immunopharmacol. 2009;9:614-619. https://doi.org/10.1016/j.intimp.2009.02.002
  56. Padmabathi B, Rath PC, Rao AR, Singh RP. Roots of Withania somnbifera inhibit forestomach and skin carcinogenesis in mice. Evid Based Complement Alternat Med. 2005;2:99-105. https://doi.org/10.1093/ecam/neh064
  57. Pandit S, Chang KW, Jeon JG. Effects of Withania somnifera on the growth and virulence properties of Streptococcus mutans and Streptococcus sobrinus at sub-MIC levels. Anaerobe. 2013;19:1-8. https://doi.org/10.1016/j.anaerobe.2012.10.007
  58. Pant M, Ambwani T, Umapathi V. Antiviral Activity of Ashwagandha Extract on Infectious Bursal Disease Virus Replication. Ind J Sci Tech. 2012;5:2750-2751.
  59. Patel K, Singh RB, Patel DK. Pharmacological and analytical aspects of withaferin-A: A concise report of current scientific literature. Asia Pac J Reproduction. 2013;2:238-243. https://doi.org/10.1016/S2305-0500(13)60154-2
  60. Paval J, Kaitheri SK, Potu BK, Govindan S, Kumar RS, Narayanan SN, Moorkoth S. Comparing the anti-arthritic activities of the plants Justicia gendarussa Burm F. and Withania somnifera Linn. Int J Green Pharm. 2009;3:281-284. https://doi.org/10.4103/0973-8258.59732
  61. 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;6:12-18.
  62. Prabu PC, Panchapakesan S, Raj CD. Acute and sub-acute oral toxicity assessment of the hydroalcoholic extract of Withania somnifera roots in Wistar rats. Phytother Res. 2013;27:1169-1178. https://doi.org/10.1002/ptr.4854
  63. Puri HS. Rasayana: Ayurvedic Herbs for Longevity and Rejuvenation (Traditional Herbal Medicines for Modern Times). 1st ed. (London, England: CRC press), 2002.
  64. RajaSankar S, Manivasagam T, Sankar V, Prakash S, Muthusamy R, Krishnamurti A, Surendran S. Withania somnifera root extract improves catecholamines and physiological abnormalities seen in a Parkinson's disease model mouse. J Ethnopharmacol. 2009;125:369-373. https://doi.org/10.1016/j.jep.2009.08.003
  65. Roy RV, Suman S, Das TP, Luevano JE, Damodaran C. Withaferin-A a steroidal lactone from Withania somnifera, induces mitotic catastrophe and growth arrest in prostate cancer cells. J Nat Prod. 2013;76:1909-1915. https://doi.org/10.1021/np400441f
  66. Sabina EP, Chandel S, Rasool MK. Evaluation of analgesic, antipyretic and ulcerogenic effect of Withaferin-A. Int J Integr Biol. 2009;6:52-56.
  67. Sabina EP, Rasool M, Vedi M, Navaneethan D, Ravichander M, Parthasarthy P, Thella SR. Hepatoprotective and antioxidant potential of Withania somnifera against paracetamol-induced liver damage in rats. Int J Pharmacy Pharm Sci. 2013;5:648-651.
  68. Sachdeva H, Sehgal R, Kaur S. Studies on the protective and immunomodulatory efficacy of Withania somnifera along with cisplatin against experimental visceral leishmaniasis. Parasitol Res. 2013;112:2269-2280. https://doi.org/10.1007/s00436-013-3387-2
  69. sandhu JS, Shah B, Shenoy S, Chauhan S, Lavekar GS, Padhi MM. Effects of Withania somnifera (Ashwagandha) and Terminalia arjuna (Arjuna) on physical performance and cardiorespiratory endurance in healthy young adults. Int J Ayurveda Res. 2010;1:144-149. https://doi.org/10.4103/0974-7788.72485
  70. Santhi N, Aishwarya S. Insights from the molecular docking of withanolide derivatives to the target protein PknG from Mycobacterium tuberculosis. Bioinformation. 2011;7:1-4. https://doi.org/10.6026/97320630007001
  71. Sarangi A, Jena S, Sarangi AK, Swain B. Anti-diabetic effects of Withania somnifera root and leaf extracts on streptozotocin induced diabetic rats. J Cell Tissue Res. 2013;13:3597.
  72. Scalbert A. Antimicrobial properties of tannins. Phytochem. 1991;30:3875-3883. https://doi.org/10.1016/0031-9422(91)83426-L
  73. Schliebs R, Liebmann A, Bhattacharya SK, Kumar A, Ghosal S, Bigl B. 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;30:181-190. https://doi.org/10.1016/S0197-0186(96)00025-3
  74. Sehgal N, Gupta A, Valli RK, Datt Joshi S, Mills JT, Hamel E, Khanna P, Jain SC, Thakur SS, Ravindranath V. Withania somnifera reverses Alzheimer's disease pathology by enhancing low-density lipoprotein receptor-related protein in liver. Proc Natl Acad Sci USA. 2012;109:3510-3515. https://doi.org/10.1073/pnas.1112209109
  75. Shahriar M, Alam F, Uddin MMN. Analgesic and meuropharmacological activity of Withania somnifera root. Int J Pharm. 2014;4:203-208.
  76. Sharada AC, Emerson Solomon F, Uma Devi P. Toxicity of Withania somnifera root extract in rats and mice. Pharm. Biol. 1993;31:205-212. https://doi.org/10.3109/13880209309082943
  77. Sharma S, Sharma V, Pracheta, Sharma S. Therapeutic potential of hydromethanolic root extract of Withania somnifera on neurological parameters in swiss albino mice subjected to lead mitrate. Int J Curr Pharm Res. 2011;3:52-56.
  78. Sharma U, Velpandian T, Sharma P, Singh S. Evaluation of anti-leishmanial activity of selected Indian plants known to have antimicrobial properties. Parasitol Res. 2009;105:1287-1293. https://doi.org/10.1007/s00436-009-1554-2
  79. Shenoy S, Chaskar U, Sandhu JS, Paadhi MM. Effects of eight-week supplementation of Ashwagandha on cardiorespiratory endurance in elite Indian cyclists. J Ayurveda Integr Med. 2012;3:209-214. https://doi.org/10.4103/0975-9476.104444
  80. Shimmi SC, Jahan N, Sultana N. Effect of Ashwagandha (Withania somnifera) root extract against gentamicin induced changes of serum urea and creatinine levels in rats. J Bangladesh Soc Physiol. 2011;6:84-89.
  81. Shukla KK, Mahdi AA, Mishra V, Rajender S, Sankhwar SN, Patel D, Das M. Withania somnifera improves semen quality by combating oxidative stress and cell death and improving essential metal concentrations. Reprod Biomed Online. 2011;22:421-427. https://doi.org/10.1016/j.rbmo.2011.01.010
  82. Singariya P, Mourya KK, Kumar P. Antimicrobial activity of the crude extracts of Withania somnifera and Cenchrus setigerus in vitro. Phcog J. 2012;4:60-65. https://doi.org/10.5530/pj.2012.27.10
  83. Singh B, Saxena AK, Chandan BK, Gupta DK, Bhutani KK, Anand KK. Adaptogenic activity of a novel, withanolide free aqueous fraction from the roots of Withania somnifera Dun. Phytother Res. 2001;15:311-318. https://doi.org/10.1002/ptr.858
  84. Singh G, Kumar P. Antibacterial potential of alkaloids of Withania somnifera L. & Euphorbia hirta L. Int J Pharmacy Pharm Sci. 2012;4:78-81.
  85. Singh G, Kumar P. Evaluation of antimicrobial efficacy of flavonoids of Withania somnifera L. Indian J Pharm Sci. 2011;73:473-478.
  86. Singh N, Verma P, Pandey BR, Gilca M. Role of Withania somnifera in prevention and treatment of cancer: An overview. Int J Pharm Sci Drug Res. 2011;3:274-279.
  87. Singh SP, Tanwer BS, Khan M. Antifungal potential of ashwagandha against some pathogenic fungi. Int J Biopharm. 2010;1:72-74.
  88. Soman S, Anju TR, Jayanarayanan S, Antony S, Paulose CS. 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. 2013;27:484-491. https://doi.org/10.1016/j.yebeh.2013.01.007
  89. Soman S, Korah PK, Jayanarayanan S, Mathew J, Paulose CS. 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;37:1915-1927. https://doi.org/10.1007/s11064-012-0810-5
  90. Thaiparambil JT, Bender L, Ganesh T, Kline E, Patel P, Liu Y, Tighiouart M, Vertino PM, Harvey RD, Garcia A, Marcus AI. Withaferin-A inhibits breast cancer invasion and metastasis at sub-cytotoxic doses by inducing vimentin disassembly and serine 56 phosphorylation. Int J Cancer. 2011;129:2744-2755. https://doi.org/10.1002/ijc.25938
  91. Udayakumar R, Kasthurirengan S, Mariashibu TS, Rajesh M, Anbazhagan VR, Kim SC, Ganapathi A, Choi CW. Hypoglycaemic and hypolipidaemic effects of Withania somnifera root and leaf extracts on alloxan-induced diabetic rats. Int J Mol Sci. 2009;10:2367-2382. https://doi.org/10.3390/ijms10052367
  92. Um HJ, Min KJ, Kim DE, Kwon TK. Withaferin-A inhibits JAK/STAT3 signaling and induces apoptosis of human renal carcinoma Caki cells. Biochem Biophys Res Commun. 2012;427:24-29. https://doi.org/10.1016/j.bbrc.2012.08.133
  93. Varma D, Kumar R, Namboothiri INN. Synthesis of withasomnines and their non-natural analogues from aldehydes and 4-Nitro-1-butanol in three steps. J Org Chem. 2013;78:3482-3486. https://doi.org/10.1021/jo400207u
  94. Visavadiya NP, Narasimhacharya AV. Hypocholesteremic and antioxidant effects of Withania somnifera (Dunal) in hypercholesteremic rats. Phytomedicine. 2007;14:136-142. https://doi.org/10.1016/j.phymed.2006.03.005
  95. Wadhwa R, singh R, Gao R, Shah N, Widodo N, Nakamoto T, Ishida Y, Terao K, Kaul SC. Water extract of Ashwagandha leaves has anticancer activity: identification of an active component and its mechanism of action. PLoS One. 2013;8:e77189. https://doi.org/10.1371/journal.pone.0077189
  96. Wijeratne EM, Xu YM, Scherz-Shouval R, Marron MT, Rocha DD, Liu MX, Costa-Lotufo LV, Santagata S, Lindquist S, Whitesell L, Gunatilaka AA. Structure-activity relationships for withanolides as inducers of the cellular heat-shock response. J Med Chem. 2014;57:2851-2863. https://doi.org/10.1021/jm401279n
  97. Yadav B, Bajaj A, Saxena M, Saxena AK. In vitro anticancer activity of the Root, stem and leaves of Withania somnifera against various human cancer cell lines. Indian J Pharm Sci. 2010;72:659-663. https://doi.org/10.4103/0250-474X.78543
  98. Yang H, Wang Y, Cheryan VT, Wu W, Cui CQ, Polin LA, Pass HI, Dou QP, Rishi AK, Wali A. Withaferin A inhibits the proteasome activity in mesothelioma in vitro and in vivo. PLoS One. 2012;7:e41214. https://doi.org/10.1371/journal.pone.0041214
  99. Yang Z, Garcia A, Xu S, Powell DR, Vertino PM, Singh S, Marcus AI. Withania somnifera root extract inhibits mammary cancer metastasis and epithelial to mesenchymal transition. PLoS One. 2013;8:e75069. https://doi.org/10.1371/journal.pone.0075069
  100. Yu Y, Hamza A, Zhang T, Gu M, Zou P, Newman B, Li Y, Gunatilaka AA, Zhan CG, Sun D. Withaferin A targets heat shock protein 90 in pancreatic cancer cells. Biochem Pharmacol. 2010;79:542-551. https://doi.org/10.1016/j.bcp.2009.09.017

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  2. Gastro-protective and Anti-stress Efficacies of Monomethyl Fumarate and a Fumaria indica Extract in Chronically Stressed Rats vol.36, pp.4, 2016, https://doi.org/10.1007/s10571-015-0243-1
  3. Nootropic and Anti-Alzheimer’s Actions of Medicinal Plants: Molecular Insight into Therapeutic Potential to Alleviate Alzheimer’s Neuropathology pp.1559-1182, 2019, https://doi.org/10.1007/s12035-018-1420-2
  4. A bioassay system for pharmacological standardization of Withania somnifera derived herbal remedies vol.9, pp.1, 2019, https://doi.org/10.5667/tang.2018.0023
  5. Effects of Ashwagandha ( Withania somnifera ) on VO 2max : A Systematic Review and Meta-Analysis vol.12, pp.4, 2015, https://doi.org/10.3390/nu12041119
  6. Chronic Stress and Oxidative Stress as Common Factors of the Pathogenesis of Depression and Alzheimer’s Disease: The Role of Antioxidants in Prevention and Treatment vol.10, pp.9, 2015, https://doi.org/10.3390/antiox10091439