Phytochemistry Reviews

, Volume 11, Issue 1, pp 97–112 | Cite as

Recent advances in elucidating the biological properties of Withania somnifera and its potential role in health benefits

  • Nadia Alam
  • Monzur Hossain
  • Md. Ibrahim Khalil
  • Mohammed Moniruzzaman
  • Siti Amrah Sulaiman
  • Siew Hua Gan
Article

Abstract

Withania somnifera (L.) Dunal (Solanaceae), also known as ashwagandha, is an important medicinal plant that is widely used as a home remedy for several diseases in the Indian subcontinent and other parts of the world. W. somnifera is a dietary supplement composed of various nutrients, polyphenols and alkaloids that have free radical scavenging capacity, as well as other chemical constituents that possess anti-inflammatory, antitumor, anti-stress, antioxidant, immunomodulatory, and rejuvenating properties. The mechanism of action for these properties are not fully understood. W. somnifera also appears to influence the endocrine, cardiopulmonary and central nervous systems. Toxicity studies reveal that W. somnifera can be used without side effects. The findings presented in this review are very encouraging and indicate that this herb should be studied more extensively to confirm these results and to reveal other potential therapeutic effects.

Keywords

W. somnifera Chemical constituents Antioxidant Therapeutic effects Toxicity 

Abbreviations

ACP

Phosphatase

ADP

Adenosine diphosphate

ALP

Alkaline phosphatase

ALT

Alanine transaminase

AST

Aspartate transaminase

ATP

Adenosine triphosphate

CAT

Catalase

DM

Diabetes mellitus

ESR

Erythrocyte sedimentation

G6P

Glucose-6-phosphatase

GABA

Gamma aminobutyric acid

GAG

Glycosaminoglycan

GERL

Golgi-endoplasmic reticulum-lysosomes

GlcS

Glucosamine sulphate

GPx

Glutathione peroxidase

GSH

Glutathione

GST

Glutathione-S-transferase

HP

Hydroperoxide

HPA

Hypothalamic pituitary adrenal

LD50

Lethal dose 50%

LPO

Lipid peroxidation

MDA

Malondialdihyde

MI

Myocardial infarction

MIR

Myocardial ischemia–reperfusion injury

NO

Nitric oxide

SOD

Superoxide dismutase

STDs

Sexually transmitted diseases

T3

Triiodothyronine

T4

Thyroxine

TBARS

Thiobarbituric acid reactive substances

WSG

W. somnifera glycowithanolides

Notes

Acknowledgments

This study was financially supported by a Universiti Sains Malaysia RU grant (grant no. 1001/PPSP/8120201 and 1001/PPSP/815058). The authors would like to acknowledge the Department of Botany, Rajshahi University, Bangladesh and the Department of Pharmacology, School of Medical Sciences, Universiti Sains Malaysia for facilitating for this study.

References

  1. Alfonso D, Bernardinelli G, Kapetanidis I (1993) Withanolides from Iochroma coccineum. Phytochemistry 34:517–521CrossRefGoogle Scholar
  2. Al-Hindawi MK, Al-Khafaji SH, Abdul-Nabi MH (1992) Anti-granuloma activity of Iraqi Withania somnifera. J Ethnopharmacol 37:113–116PubMedCrossRefGoogle Scholar
  3. Anbalagan K, Sadique J (1981) Influence of an Indian medicine (Ashwagandha) on acutephase reactants in inflammation. Indian J Exp Biol 19:245–249PubMedGoogle Scholar
  4. Anbalagan K, Sadique J (1984) Role of prostaglandins in acute phase proteins in inflammation. Biochem Med 31:236–245PubMedCrossRefGoogle Scholar
  5. Andallu B, Radhika B (2000) Hypoglycemic, diuretic and hypocholesterolemic effect of winter cherry (Withania somnifera) root. Indian J Exp Biol 38:607–609PubMedGoogle Scholar
  6. Anonymous (2004) Monograph: Withania somnifera. Altern Med Rev 9:211–214Google Scholar
  7. Archana R, Namasivayam A (1999) Antistressor effect of Withania somnifera. J Ethnopharmacol 64:91–93PubMedCrossRefGoogle Scholar
  8. Arora S, Dhillon S, Rani G, Nagpal A (2004) The in vitro antibacterial/synergistic activities of Withania somnifera extracts. Fitoterapia 75:385–388PubMedCrossRefGoogle Scholar
  9. Arseculeratne SN, Gunatilaka AA, Panabokke RG (1985) Studies of medicinal plants of Sri Lanka. Part 14: toxicity of some traditional medicinal herbs. J Ethnopharmacol 13:323–335PubMedCrossRefGoogle Scholar
  10. Bargagna-Mohan P, Ravindranath PP, Mohan R (2006) Small molecule anti-angiogenic probes of the ubuquitin proteasome pathway: potential applications to choroidal neovascularization. Invest Ophthalmol Vis Sci 47:4138–4145PubMedCrossRefGoogle Scholar
  11. Begum VH, Sadique J (1987) Effect of Withania somnifera on glycosaminoglycan synthesis in carrageenin-induced air pouch granuloma. Biochem Med Metab Biol 38:272–277PubMedCrossRefGoogle Scholar
  12. Begum VH, Sadique J (1988) Long-term effect of herbal drug Withania somnifera on adjuvant-induced arthritis in rats. Indian J Exp Biol 26:877–882PubMedGoogle Scholar
  13. Bhatnagar M, Jain CP, Sisodia SS (2005) Anti-ulcer activity of Withania somnifera in stress plus pyloric ligation induced gastric ulcer in rats. J Cell Tissue Res 5:287–292Google Scholar
  14. Bhattacharya SK, Muruganandam AV (2003) Adaptogenic activity of Withania somnifera: an experimental study using a rat model of chronic stress. Pharmacol Biochem Behav 75:547–555PubMedCrossRefGoogle Scholar
  15. Bhattacharya S, Goel R, Kaur R, Ghosal S (1987) Anti-stress activity of Sitoindosides VII and VIII, new Acylsterylglucosides from Withania Somnifera. Phytother Res 1:32–39CrossRefGoogle Scholar
  16. Bhattacharya SK, Bhattacharya A, Sairam K, Ghosal S (2000) Anxiolytic-antidepressant activity of Withania somnifera glycowithanolides: an experimental study. Phytomedicine 7:463–469PubMedCrossRefGoogle Scholar
  17. 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 74:1–6PubMedCrossRefGoogle Scholar
  18. Bogdan C (2001) Nitric oxide and the immune response. Nat Immunol 2:907–916PubMedCrossRefGoogle Scholar
  19. Bone K (1996) Clinical applications of Ayurvedic and Chinese herbs. Phytotherapy Press, Warwick, pp 137–141Google Scholar
  20. Davis L, Kuttan G (2002) Effect of Withania somnifera on CTL activity. J Exp Clin Cancer Res 21:115–118PubMedGoogle Scholar
  21. Devi PU (1996) W. somnifera Dunal (Ashwagandha): potential plant source of a promising drug for cancer chemotherapy and radiosensitization. Indian J Exp Biol 34:927–932PubMedGoogle Scholar
  22. Dhuley JN (1998) Effect of ashwagandha on lipid peroxidation in stress-induced animals. J Ethnopharmacol 60:173–178PubMedCrossRefGoogle Scholar
  23. Dhuley JN (2000) Adaptogenic and cardioprotective action of ashwagandha in rats and frogs. J Ethnopharmacol 70:57–63PubMedCrossRefGoogle Scholar
  24. Dhuley JN (2001) Nootropic-like effect of Ashwagandha (Withania somnifera). Phytother Res 15:311–318CrossRefGoogle Scholar
  25. Elsakka M, Grigorescu E, Stanescu U (1990) New data referring to chemistry of Withania somnifera species. Rev Med Chir Soc Med Nat Iasi 94:385–387PubMedGoogle Scholar
  26. Ghosal S, Lal J, Srivastava RS, Bhattacharya SK, Upadhyay SN, Jaiswal AK, Chattopadhyay U (1989) Immunomodulatory and CNS effects of Sitoindosides IX and X, Two new Glycowithanolides from Withania somnifera. Phytother Res 3:201–206CrossRefGoogle Scholar
  27. Ghosh M (2009) Purification of a lectin-like antifungal protein from the medicinal herb, Withania somnifera. Fitoterapia 80:91–95PubMedCrossRefGoogle Scholar
  28. Girish KS, Ushanandini S, Harish Kumar K, Nagaraju S, Govindappa M, Vedavathi M, Kemparaju K (2006) Antimicrobial properties of a non-toxic glycoprotein (WSG) from Withania somnifera (Ashwagandha). J Basic Microbiol 46:365–374PubMedCrossRefGoogle Scholar
  29. Glotter E (1991) Withanolides and related ergostane-type steroids. Nat Prod Rep 8:415–440PubMedCrossRefGoogle Scholar
  30. Grandhi A (1994) Comparative pharmacological investigation of ashwagandha and ginseng. J Ethnopharmacol (Ireland) 3:131–135CrossRefGoogle Scholar
  31. Gupta GL, Rana AC (2007) Withania somnifera (Ashwagandha): a review. Pharmacogn Rev 1:129–136Google Scholar
  32. Gupta AP, Verma RK, Misra HO, Gupta MM (1996) Quantitative determination of withaferin A in different plant parts of Withania somnifera by TLC densitometry. J Med Aromat Plant Sci 18:788–790Google Scholar
  33. Gupta SK, Dua A, Vohra BP (2003) W. somnifera (Ashwagandha) attenuates antioxidant defense in aged spinal cord and inhibits copper induced lipid peroxidation and protein oxidative modifications. Drug Metabol Drug Interact 19:211–222PubMedCrossRefGoogle Scholar
  34. Gupta SK, Mohanty I, Talwar KK, Dinda A, Joshi S, Bansal P, Saxena AK, Arya DS (2004) Cardioprotection from ischemia and reperfusion injury by Withania somnifera: a hemodynamic, biochemical and histopathological assessment. Mol Cell Biochem 260:39–47PubMedCrossRefGoogle Scholar
  35. Hamza A, Amin A, Daoud S (2008) The protective effect of a purified extract of W. somnifera against doxorubicin-induced cardiac toxicity in rats. Cell Biol Toxicol 24:63–73PubMedCrossRefGoogle Scholar
  36. Harikrishnan B, Subramanian P, Subash S (2008) Effect of Withania Somnifera root powder on the levels of circulatory lipid peroxidation and liver marker enzymes in chronic hyperammonemia. E-J Chem 5:872–877Google Scholar
  37. Hemalatha S, Wahi AK, Singh PN, Chansouria JP (2006) Hypolipidemic activity of aqueous extract of Withania coagulans Dunal in albino rats. Phytother Res 20:614–617PubMedCrossRefGoogle Scholar
  38. 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 Therapy 5:1434–1445CrossRefGoogle Scholar
  39. Iuvone T, Esposito G, Capasso F, Izzo A (2003) Induction of nitric oxide synthase expression by Withania somnifera in macrophages. Life Sci 72:1617–1625PubMedCrossRefGoogle Scholar
  40. Jaiswal D, Rai PK, Watal G (2010) Hypoglycemic and antidiabetic effects of Withania coagulans fruit ethanolic extract in normal and streptozotocin-induced diabetic rats. J Food Biochem 34:764–778Google Scholar
  41. Jaleel CA (2009) Antioxidant profile changes in leaf and root tissues of Withania somnifera Dunal. Plant Omics J 2:163–168Google Scholar
  42. Jaleel CA, Lakshmanan GMA, Gomathinayagam M, Panneerselvam R (2008) Triadimefon induced salt stress tolerance in W. somnifera and its relationship to antioxidant defense system. S Afr J Bot 74:126–132CrossRefGoogle Scholar
  43. Jayaprakasam B, Zhang Y, Seeram N, Nair M (2003) Growth inhibition of tumor cell lines by withanolides from Withania somnifera leaves. Life Sci 74:125–132PubMedCrossRefGoogle Scholar
  44. Johri S, Jamwal U, Rasool S, Kumar A, Verma V, Qazi GN (2005) Purification and characterization of peroxidases from Withania somnifera (AGB 002) and their ability to oxidize IAA. Plant Sci 169:1014–1021CrossRefGoogle Scholar
  45. Kaileh M, Vanden Berghe W, Heyerick A, Horion J, Piette J, Libert C, De Keukeleire D, Essawi T, Haegeman G (2007) Withaferin A strongly elicits IkappaB kinase beta hyper-phosphorylation concomitant with potent inhibition of its kinase activity. J Biol Chem 282:4253–4264PubMedCrossRefGoogle Scholar
  46. Kambizia L, Afolayan AJ (2008) Extracts from Aloe ferox and Withania somnifera inhibit Candida albicans and Neisseria gonorrhoea. Afr J Biotechnol 7:12–15Google Scholar
  47. Kambizia L, Goosenb BM, Taylorc MB, Afolayan AJ (2007) Anti-viral effects of aqueous extracts of Aloe ferox and Withania somnifera on herpes simplex virus type 1 in cell culture. S Afr J Sci 103:359–360Google Scholar
  48. Kaur P, Mathur S, Sharma M, Tiwari M, Sdvastava KK, Chandra R (2001) A biologically active constituent of W. somnifera (ashwagandha) with antistress activity. Indian J Clin Biochem 16:195–198CrossRefGoogle Scholar
  49. Kinghorn AD, Su B-N, Jang DS, Chang LC, Lee D, Gu J-Q, Carcache-Blanco EJ, Pawlus AD, Lee SK, Park EJ, Cuendet M, Gills JJ, Bhat K, Park HS, Mata-Greenwod E, Song LL, Jang M, Pezzuto JM (2004) Natural inhibitors of carcinogenesis. Planta Med 70:691–705PubMedCrossRefGoogle Scholar
  50. Kulkarni SK, George B, Mathur R (1998) Protective effect of Withania somnifera root extract on electrographic activity in a lithiumpilocarpine model of status epilepticus. Phytother Res 12:451–453CrossRefGoogle Scholar
  51. Kuttan G (1996) Use of Withania somnifera Dunal as an adjuvant during radiation therapy. Indian J Exp Biol 34:854–856PubMedGoogle Scholar
  52. Mahesh B, Satish S (2008) Antimicrobial activity of some important medicinal plant against plant and human pathogens. World J Agric Sci 4:839–843Google Scholar
  53. Malhotra CL, Mehta VL, Prasad K, Das PK (1965) Studies on Withania ashwagandha, Kaul. IV. The effect of total alkaloids on the smooth muscles. Indian J Physiol Pharmacol 9:9–15PubMedGoogle Scholar
  54. Mary NK, Babu BH, Padikkala J (2003) Antiatherogenic effect of caps HT2, an herbal Ayurvedic medicine formulation. Phytomedicine 10:474–482PubMedCrossRefGoogle Scholar
  55. Mehta AK, Binkley P, Gandhi SS, Ticku MK (1991) Pharmacological effects of Withania somnifera root extract on GABAA receptor complex. Indian J Med Res 94:312–315PubMedGoogle Scholar
  56. Mirjalili MH, Moyano E, Bonfill M, Cusido RM, Palazón J (2009) Steroidal lactones from Withania somnifera, an ancient plant for novel medicine. Molecules 14:2373–2393PubMedCrossRefGoogle Scholar
  57. Mohan IK, Kumar KV, Naidu MU, Khan M, Sundaram C (2006) Protective effect of CardiPro against doxorubicin-induced cardiotoxicity in mice. Phytomedicine 13:222–229PubMedCrossRefGoogle Scholar
  58. Mohanty I, Arya DS, Dinda A, Talwar KK, Joshi S, Gupta SK (2004) Mechanisms of cardioprotective effect of Withania somnifera in experimentally induced myocardial infarction. Basic Clin Pharmacol Toxicol 94:184–190PubMedGoogle Scholar
  59. Mohanty IR, Arya DS, Gupta SK (2008) Withania somnifera provides cardioprotection and attenuates ischemia-reperfusion induced apoptosis. Clin Nutr 27:635–642PubMedCrossRefGoogle Scholar
  60. Owais M, Sharad KS, Shehbaz A, Saleemuddin M (2005) Antibacterial efficacy of Withania somnifera (ashwagandha) an indigenous medicinal plant against experimental murine salmonellosis. Phytomedicine 12:229–235PubMedCrossRefGoogle Scholar
  61. Panda S, Kar A (1998) Changes in thyroid hormone concentrations after administration of ashwagandha root extract to adult male mice. J Pharm Pharmacol 50:1065–1068PubMedCrossRefGoogle Scholar
  62. Panda S, Kar A (1999) Withania somnifera and Bauhinia pupurea in the regulation of circulating thyroid hormone concentrations in female mice. J Ethnopharmacol 67:233–239PubMedCrossRefGoogle Scholar
  63. Prakash J, Gupta SK, Dinda AK (2002) Withania somnifera root extract prevents DMBA-induced quamous cell carcinoma of skin in Swiss albino mice. Nutr Cancer 42:91–97PubMedCrossRefGoogle Scholar
  64. Prince PSM, Selvaraju S, Devika PT, Vaithianathan M (2008) Cardioprotective effect of Marutham’ a polyherbal formulation on isoproterenol induced myocardial infarction in Wistar rats. Fitoterapia 79:433–438PubMedCrossRefGoogle Scholar
  65. Rastogi RP, Mehrotra BN (1998) Compendium of Indian medicinal plants. Central Drug Research Institute 6Google Scholar
  66. Ray AB, Gupta M (1994) Withasteroids, a growing group of naturally occurring steroidal lactones. Prog Chem Org Nat Prod 63:2–106Google Scholar
  67. Sandhu JS, Shah B, Shenoy S, Chauhan S, Lavekar GS, Padhi MM (2010) Effects of Withania somnifera (Ashwagandha) and Terminalia arjuna (Arjuna) on physical performance and cardiorespiratory endurance in healthy young adults. Int J Ayurveda Res 1:144–149PubMedCrossRefGoogle Scholar
  68. Sangwan RS, Chaurasiya ND, Misra LN, Lal P, Uniyal GC, Sharma R, Sangwan NS, Suri KA, Qazi GN, Tuli R (2004) Phytochemical variability in commercial herbal products and preparations of Withania somnifera (ashwagandha). Curr Sci 86:461–465Google Scholar
  69. Schliebs R, Liebmann SK, Kumar A, Ghosal S, Bigl V (1973) Systemic administration of defined extracts from Withania somnifera (Indian ginseng) and Shilajit differentially affects choilinergic but not glutamatergic and GAB Aergic marker in rat brain. Neurochem Int 30:181–190CrossRefGoogle Scholar
  70. Senthilnathan P, Padmavathi R, Banu SM, Sakthisekaran D (2006) Enhancement of antitumor effect of paclitaxel in combination with immunomodulatory Withania somnifera on benzo(a)pyrene induced experimental lung cancer. Chem Biol Interact 159:180–185PubMedCrossRefGoogle Scholar
  71. Sharada AC, Solomon FE, Uma Devi P (1993) Toxicity of Withania somnifera root extract in rats and mice. Int J Pharmacogn 31:205–212CrossRefGoogle Scholar
  72. Sharma S, Dahanukar S, Karandikar SM (1985) Effects of long-term administration of the roots of ashwagandha and shatavari in rats. Indian Drugs 29:133–139Google Scholar
  73. Singh G, Sharma PK, Dudhe R, Singh S (2010) Biological activities of Withania somnifera. Ann Bioll Res 1:56–63Google Scholar
  74. Somasundaram S, Sadique J, Subramoniam A (1983) Influence of extra-intestinal inflammation on the in vitro absorption of 14C-glucose and the effects of anti-inflammatory drugs in the jejunum of rats. Clin Exp Pharmacol Physiol 10:147–152PubMedCrossRefGoogle Scholar
  75. Subaraju GV, Vanisree M, Rao CV, Sivaramakrishna C, Sridhar P, Jayaprakasam B, Nair MG (2006) Ashwagandhanolide, a bioactive dimeric thiowithanolide isolated from the roots of Withania somnifera. J Nat Prod 69:1790–1792CrossRefGoogle Scholar
  76. Sumantran VN, Chandwaskar R, Boddul S, Patwardhan B, Chopra A, Wagh UV (2008) The relationship between chondroprotective and antiinflammatory effects of Withania somnifera root and glucosamine sulphate on human osteoarthritic cartilage in vitro. Phytother Res 22:1342–1348PubMedCrossRefGoogle Scholar
  77. Thirunavukkarasu M, Penumathsa S, Juhasz B, Zhan L, Bagchi M, Yasmin T, Shara MA, Thatte HS, Bagchi D, Maulik N (2006) Enhanced cardiovascular function and energy level by a novel chromium (III)-supplement. Biofactors 27:53–67PubMedCrossRefGoogle Scholar
  78. Tohda C, Kuboyama T, Komatsu K (2005) Search for natural products related to regeneration of the neuronal network. Neurosignals 44:34–45CrossRefGoogle Scholar
  79. Tripathi AK, Dey S, Singh RH, Dey PK (1998) Alterations in the sensitivity of 5th receptor subtypes following chronic Asvagandha treatment in rats. Anc Sci Life 17:168–181Google Scholar
  80. Udayakumar R, Kasthurirengan S, Mariashibu TS, Rajesh M, Ramesh Anbazhagan V, Kim SC, Ganapathi A, Choi CW (2009) Hypoglycaemic and hypolipidaemic effects of Withania somnifera root and leaf extracts on alloxan-induced diabetic rats. Int J Mol Sci 10:2367–2382PubMedCrossRefGoogle Scholar
  81. Udayakumar R, Kasthurirengan S, Vasudevan A, Mariashibu TS, Rayan JJS, Choi CW, Ganapathi A, Kim SC (2010) Antioxidant effect of dietary supplement Withania somnifera L. Reduce blood glucose levels in alloxan-induced diabetic rats. Plant Foods Hum Nutr 65:91–98PubMedCrossRefGoogle Scholar
  82. Verma P, Srivastava SK, Nath A (2009) Stimulatory effect of Withenia somnifera on secretion and endocytotic pathways in the hepatic cell of Clarias batrachus (Linn.). J Ecophysiol Occupat Health 9:203–209Google Scholar
  83. Visavadiya NP, Narasimhacharya AV (2007) Hypocholesteremic and antioxidant effects of Withania somnifera (Dunal) in hypercholesteremic rats. Phytomedicine 14:136–142PubMedCrossRefGoogle Scholar
  84. Winters M (2006) Ancient medicine, modern use of Withania somnifera and its potential role in integrative oncology. Altern Med Rev 11:269–277PubMedGoogle Scholar
  85. Zhao J, Nakamura N, Hattori M, Kuboyama T, Tohda C, Komats K (2002) Withanolide derivatives from the roots of Withania somnifera and their neurite outgrowth activities. Chem Pharm Bull (Tokyo) 50:760–765CrossRefGoogle Scholar
  86. Ziauddin M, Phansalkar N, Patki P, Diwanay S, Patwardhan B (1996) Studies on the immunomodulatory effects of Ashwagandha. J Ethnopharmacol 50:69–76PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Nadia Alam
    • 1
  • Monzur Hossain
    • 1
  • Md. Ibrahim Khalil
    • 2
    • 3
  • Mohammed Moniruzzaman
    • 2
  • Siti Amrah Sulaiman
    • 2
  • Siew Hua Gan
    • 4
  1. 1.Department of BotanyRajshahi UniversityRajshahiBangladesh
  2. 2.Department of Pharmacology, School of Medical SciencesUniversiti Sains MalaysiaKubang KerianMalaysia
  3. 3.Department of Biochemistry and Molecular BiologyJahangirnagar UniversitySavar, DhakaBangladesh
  4. 4.Human Genome Centre, School of Medical SciencesUniversiti Sains MalaysiaKubang KerianMalaysia

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