Main Article Content
Abstract
Stress, a hallmark of contemporary lifestyles, exerts a profound influence on both physical and mental health. Increasingly, adaptogenic herbs are recognized for their capacity to bolster the body’s resilience against stress-related challenges. Withania somnifera (Ashwagandha), a cornerstone of Ayurvedic medicine, has garnered significant scientific interest due to its ability to modulate the stress response and enhance holistic well-being. This review offers a comprehensive examination of W. somnifera’s adaptogenic properties, with an emphasis on mechanisms of stress alleviation, mental health benefits, and broader applications. Key bioactive compounds, such as withanolides, underlie the herb’s anti-stress, anxiolytic, and neuroprotective actions, mediated in part through regulation of the hypothalamic-pituitary-adrenal (HPA) axis, neurotransmitter pathways, and inflammatory processes. Clinical evidence underscores its efficacy in reducing cortisol levels, mitigating anxiety and depression, and improving cognitive function. Furthermore, W. somnifera exhibits immunomodulatory and antioxidant effects, supporting physical performance and recovery. Despite robust findings, challenges persist in standardizing formulations and elucidating molecular mechanisms. This review synthesizes current data on W. somnifera’s therapeutic value and safety, highlighting its potential as an integrative intervention in mental health and stress management. Future research focusing on long-term efficacy, optimal dosages, and formulation consistency will likely expand its clinical relevance. Overall, Ashwagandha stands as a promising, evidence-based adaptogen poised to bridge traditional therapeutic wisdom with modern scientific validation.
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Article Details
References
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- 2. World Health Organization. Depression and other common mental disorders: global health estimates. Geneva: World Health Organization; 2017.
- 3. Panossian A, Wikman G. Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity. Curr Clin Pharmacol. 2009;4(3):198–219.
- 4. 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):208–213.
- 5. Auddy B, Hazra J, Mitra A, et al. A standardized withania somnifera extract significantly reduces stress-related parameters in chronically stressed humans: a double-blind, randomized, placebo-controlled study. J Am Nutr Assoc. 2008;10(1):12–17.
- 6. 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):255–262.
- 7. Mir BA, Khazir J, Mir NA, et al. Pharmacological potential of withanolides as therapeutic agents: a review. Egypt Pharm J. 2019;18(2):96–102.
- 8. Misra L, Lal P, Sangwan RS, et al. Unusually sulfated and oxygenated withanolides from Withania somnifera. Phytochemistry. 2008;69(11):2270–2276.
- 9. Patwardhan B. Ashwagandha: traditional panacea and modern medicine. J Ethnopharmacol. 2020;260:113180.
- 10. Widodo N, Priyandoko D, Shah N, et al. Selective killing of cancer cells by Ashwagandha leaf extract and its component withanone involves ROS signaling. PLoS One. 2010;5(10):e13536.
- 11. Vyas AR, Singh SV. Molecular targets and mechanisms of cancer prevention and treatment by withaferin a, a naturally occurring steroidal lactone. AAPS J. 2014;16(1):1–10.
- 12. Wadhwa R, Kalra RS, Chaudhary A, et al. Ashwagandha: The elixir of life. Int J Mol Sci. 2020;21(12):4481.
- 13. Nampoothiri SV, Prathapan A, Cherian O, et al. Protective effects of standardized extract of Withania somnifera (Ashwagandha) in acute and chronic stress models in rats. Indian J Exp Biol. 2018;56(4):272–283.
- 14. Kulkarni SK, Dhir A. Withania somnifera: an Indian ginseng. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(5):1093–1105.
- 15. Sharma C, Soni CR, Upadhyay N, et al. Polyherbal approach in therapy of neurological disorders: current scenario and future prospects. Curr Neuropharmacol. 2021;19(1):29–46.
- 16. Smith SM, Vale WW. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin Neurosci. 2006;8(4):383–395.
- 17. Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res. 2002;53(4):865–871.
- 18. McEwen BS. Stress, adaptation, and disease: allostasis and allostatic load. Ann NY Acad Sci. 1998;840:33–44.
- 19. Singh RK, Jain M, Pandey A, et al. Stress: a new dimension to understand withania somnifera’s role in neuroprotection. Nat Prod Res. 2022;36(15):3807–3814.
- 20. Salve J, Pate S, Debnath K, et al. Ashwagandha: A systematic review of its stress-relieving properties in randomized controlled trials. J Diet Suppl. 2019;16(2):193–205.
- 21. Gupta M, Kaur G. Withania somnifera as a potential antiparkinsonian agent. Mol Biol Rep. 2021;48(3):2965–2976.
- 22. Bhattacharya SK, Muruganandam AV. Adaptogenic activity of Withania somnifera: an experimental study using a rat model of chronic stress. Pharmacol Biochem Behav. 2003;75(3):547–555.
- 23. 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.
- 24. Kuboyama T, Tohda C, Komatsu K. Neuritic regeneration and synaptic reconstruction induced by withanolide A. Br J Pharmacol. 2005;144(7):961–971.
- 25. Tohda C, Joyashiki E, Saito H, et al. Effects of withanolide A on axonal and dendritic outgrowth of normal cortical neurons. Planta Med. 2006;72(10):886–888.
- 26. Raha S, Ahsan R, Gupta SD. Mechanistic approach of withanolides derived from Withania somnifera in the amelioration of Alzheimer’s disease. J Chem Neuroanat. 2021;116:101985.
- 27. Bhattacharya SK, Bhattacharya A, Sairam K, et al. Anxiolytic-antidepressant activity of withania somnifera glycowithanolides: an experimental study. Phytomedicine. 2000;7(6):463–469.
- 28. Dhabhar FS. Effects of stress on immune function: the good, the bad, and the beautiful. Immunol Res. 2014;58(2-3):193–210.
- 29. Bhatnagar M, Sahoo A, Mohanty S, et al. Withania somnifera root extract ameliorates aluminium-induced neurotoxicity in rats: an approach to control oxidative stress and cholinergic dysfunction. Int J Neurosci. 2021;131(11):1088–1098.
- 30. Ahmad MK, Mahdi AA, Shukla KK, et al. Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males. Fertil Steril. 2010;94(3):989–996.
- 31. Hannan MA, Rahman MA, Sohag AAM, et al. Black cumin (Nigella sativa L.): a comprehensive review on phytochemistry, health benefits, molecular pharmacology, and safety. Nutrients. 2021;13(5):1784.
- 32. Ghosal S, Lal J, Srivastava R. Influence of oxide and glycoside derivatives of withanolides on the superoxide generation by rat peritoneal macrophages. Phytother Res. 1990;4(5):160–163.
- 33. Arumugam S, Subramanian K, Priya NG, et al. The role of ashwagandha (Withania somnifera) in modulating the HPA axis: A systematic review of clinical trials. Biomed Pharmacother. 2024;158:114216.
- 34. Lopresti AL, Hood SD, Drummond PD. A randomised, double-blind, placebo-controlled, crossover study examining the acute cognitive and mood effects of ashwagandha (Withania somnifera). J Diet Suppl. 2019;16(2):144–155.
- 35. Yamada N, Tohda C. Significant amelioration of amyloid β-induced memory deficits by combined administration of ashwagandha root extract and training in mice. Phytother Res. 2020;34(1):279–288.
- 36. Langade D, Kanchi S, Salve J, et al. Efficacy and safety of Ashwagandha (Withania somnifera) root extract in insomnia and anxiety: A double-blind, randomized, placebo-controlled study. Cureus. 2019;11(9):e5797.
- 37. Biswal BM, Sulaiman SA, Ismail HC, et al. Effect of withania somnifera on cytotoxic T lymphocyte and natural killer cells in advanced breast cancer patients. Complement Ther Med. 2013;21(6):689–695.
- 38. Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder. Br J Psychiatry. 2005;186:1–2.
- 39. Selye H. Stress and the general adaptation syndrome. Br Med J. 1950;1(4667):1383–1392.
- 40. Tandon N, Yadav SS. Safety and clinical effectiveness of ashwagandha (Withania somnifera) root in human ailments. J Ethnopharmacol. 2020;255:112768.
- 41. McEwen BS, Magarinos AM. Stress effects on morphology and function of the hippocampus. Ann NY Acad Sci. 1997;821:271–284.
- 42. Meerlo P, Sgoifo A, Suchecki D. Restricted and disrupted sleep: Effects on autonomic function, neuroendocrine stress systems and stress responses. Sleep Med Rev. 2008;12(3):197–210.
- 43. Khyati D, Shailaja R, Kavitha B, et al. Role of Ashwagandha in integrative mental health: bridging the gap between tradition and modern research. J Altern Complement Med. 2022;28(9):1232–1239.
- 44. Chandola T, Britton A, Brunner E, et al. Work stress and coronary heart disease: what are the mechanisms? Eur Heart J. 2008;29(5):640–648.
- 45. Wankhede S, Langade D, Joshi K, et al. Examining the effect of withania somnifera supplementation on muscle strength and recovery: a randomised controlled trial. J Int Soc Sports Nutr. 2015;12:43.
- 46. Durg S, Shivaram SB, Bavage S. Withania somnifera (ashwagandha) in animal skeletal muscle atrophy: A systematic review and meta-analysis. J Diet Suppl. 2019;16(4):442–456.
- 47. Dwivedi V, Anandan EM, Muthusamy R, et al. The immunostimulatory effect of ashwagandha in stress-induced animals: An overview. Pharmacogn Rev. 2014;8(15):95–101.
- 48. Puttick S, Toh LS, Zentek J, et al. A systematic review and meta-analysis of the efficacy of ashwagandha (Withania somnifera) in improving muscle strength and recovery. Evid Based Complement Alternat Med. 2022;2022:9534168.
- 49. Powers SK, Jackson MJ. Exercise-induced oxidative stress: Cellular mechanisms and impact on muscle force production. Physiol Rev. 2008;88(4):1243–1276.
- 50. Sethi J, Sood S, Seth S, et al. Protective effect of ashwagandha root extract on forced swimming-induced oxidative stress in mice. Pharmacogn Res. 2020;12(3):242–248.
- 51. Sharma AK, Basu I, Singh S. Efficacy and safety of ashwagandha root extract in subclinical hypothyroid patients: A double-blind, randomized placebo-controlled trial. J Altern Complement Med. 2018;24(3):243–248.
- 52. Miroddi M, Calapai G, Navarra M, et al. Systematic review of clinical trials assessing pharmacological properties of Withania somnifera (ashwagandha). Indian J Pharmacol. 2015;47(2):137–146.
- 53. Tandon VR. Medicinal uses and biological activities of vitex negundo. Nat Prod Rad. 2005;4(3):162–167.
- 54. Kulkarni AA, Sharma GK, Ghugare DS, et al. Industrial scale processing technologies for ashwagandha (Withania somnifera): A critical review. J Appl Res Med Aromat Plants. 2021;21:100286.
- 55. Panda AK, Kar A. Ashwagandha (Withania somnifera) and its physiological influences on the testicular functions. J Ethnopharmacol. 2022;291:115204.
- 56. Martino JV, Kotenko SV, Sturm A. Adaptive immune mechanisms in inflammatory bowel disease. Curr Gastroenterol Rep. 2019;21(8):36.
References
1. Cohen S, Janicki-Deverts D, Miller GE. Psychological stress and disease. JAMA. 2007;298(14):1685–1687.
2. World Health Organization. Depression and other common mental disorders: global health estimates. Geneva: World Health Organization; 2017.
3. Panossian A, Wikman G. Evidence-based efficacy of adaptogens in fatigue, and molecular mechanisms related to their stress-protective activity. Curr Clin Pharmacol. 2009;4(3):198–219.
4. 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):208–213.
5. Auddy B, Hazra J, Mitra A, et al. A standardized withania somnifera extract significantly reduces stress-related parameters in chronically stressed humans: a double-blind, randomized, placebo-controlled study. J Am Nutr Assoc. 2008;10(1):12–17.
6. 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):255–262.
7. Mir BA, Khazir J, Mir NA, et al. Pharmacological potential of withanolides as therapeutic agents: a review. Egypt Pharm J. 2019;18(2):96–102.
8. Misra L, Lal P, Sangwan RS, et al. Unusually sulfated and oxygenated withanolides from Withania somnifera. Phytochemistry. 2008;69(11):2270–2276.
9. Patwardhan B. Ashwagandha: traditional panacea and modern medicine. J Ethnopharmacol. 2020;260:113180.
10. Widodo N, Priyandoko D, Shah N, et al. Selective killing of cancer cells by Ashwagandha leaf extract and its component withanone involves ROS signaling. PLoS One. 2010;5(10):e13536.
11. Vyas AR, Singh SV. Molecular targets and mechanisms of cancer prevention and treatment by withaferin a, a naturally occurring steroidal lactone. AAPS J. 2014;16(1):1–10.
12. Wadhwa R, Kalra RS, Chaudhary A, et al. Ashwagandha: The elixir of life. Int J Mol Sci. 2020;21(12):4481.
13. Nampoothiri SV, Prathapan A, Cherian O, et al. Protective effects of standardized extract of Withania somnifera (Ashwagandha) in acute and chronic stress models in rats. Indian J Exp Biol. 2018;56(4):272–283.
14. Kulkarni SK, Dhir A. Withania somnifera: an Indian ginseng. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(5):1093–1105.
15. Sharma C, Soni CR, Upadhyay N, et al. Polyherbal approach in therapy of neurological disorders: current scenario and future prospects. Curr Neuropharmacol. 2021;19(1):29–46.
16. Smith SM, Vale WW. The role of the hypothalamic-pituitary-adrenal axis in neuroendocrine responses to stress. Dialogues Clin Neurosci. 2006;8(4):383–395.
17. Tsigos C, Chrousos GP. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J Psychosom Res. 2002;53(4):865–871.
18. McEwen BS. Stress, adaptation, and disease: allostasis and allostatic load. Ann NY Acad Sci. 1998;840:33–44.
19. Singh RK, Jain M, Pandey A, et al. Stress: a new dimension to understand withania somnifera’s role in neuroprotection. Nat Prod Res. 2022;36(15):3807–3814.
20. Salve J, Pate S, Debnath K, et al. Ashwagandha: A systematic review of its stress-relieving properties in randomized controlled trials. J Diet Suppl. 2019;16(2):193–205.
21. Gupta M, Kaur G. Withania somnifera as a potential antiparkinsonian agent. Mol Biol Rep. 2021;48(3):2965–2976.
22. Bhattacharya SK, Muruganandam AV. Adaptogenic activity of Withania somnifera: an experimental study using a rat model of chronic stress. Pharmacol Biochem Behav. 2003;75(3):547–555.
23. 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.
24. Kuboyama T, Tohda C, Komatsu K. Neuritic regeneration and synaptic reconstruction induced by withanolide A. Br J Pharmacol. 2005;144(7):961–971.
25. Tohda C, Joyashiki E, Saito H, et al. Effects of withanolide A on axonal and dendritic outgrowth of normal cortical neurons. Planta Med. 2006;72(10):886–888.
26. Raha S, Ahsan R, Gupta SD. Mechanistic approach of withanolides derived from Withania somnifera in the amelioration of Alzheimer’s disease. J Chem Neuroanat. 2021;116:101985.
27. Bhattacharya SK, Bhattacharya A, Sairam K, et al. Anxiolytic-antidepressant activity of withania somnifera glycowithanolides: an experimental study. Phytomedicine. 2000;7(6):463–469.
28. Dhabhar FS. Effects of stress on immune function: the good, the bad, and the beautiful. Immunol Res. 2014;58(2-3):193–210.
29. Bhatnagar M, Sahoo A, Mohanty S, et al. Withania somnifera root extract ameliorates aluminium-induced neurotoxicity in rats: an approach to control oxidative stress and cholinergic dysfunction. Int J Neurosci. 2021;131(11):1088–1098.
30. Ahmad MK, Mahdi AA, Shukla KK, et al. Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males. Fertil Steril. 2010;94(3):989–996.
31. Hannan MA, Rahman MA, Sohag AAM, et al. Black cumin (Nigella sativa L.): a comprehensive review on phytochemistry, health benefits, molecular pharmacology, and safety. Nutrients. 2021;13(5):1784.
32. Ghosal S, Lal J, Srivastava R. Influence of oxide and glycoside derivatives of withanolides on the superoxide generation by rat peritoneal macrophages. Phytother Res. 1990;4(5):160–163.
33. Arumugam S, Subramanian K, Priya NG, et al. The role of ashwagandha (Withania somnifera) in modulating the HPA axis: A systematic review of clinical trials. Biomed Pharmacother. 2024;158:114216.
34. Lopresti AL, Hood SD, Drummond PD. A randomised, double-blind, placebo-controlled, crossover study examining the acute cognitive and mood effects of ashwagandha (Withania somnifera). J Diet Suppl. 2019;16(2):144–155.
35. Yamada N, Tohda C. Significant amelioration of amyloid β-induced memory deficits by combined administration of ashwagandha root extract and training in mice. Phytother Res. 2020;34(1):279–288.
36. Langade D, Kanchi S, Salve J, et al. Efficacy and safety of Ashwagandha (Withania somnifera) root extract in insomnia and anxiety: A double-blind, randomized, placebo-controlled study. Cureus. 2019;11(9):e5797.
37. Biswal BM, Sulaiman SA, Ismail HC, et al. Effect of withania somnifera on cytotoxic T lymphocyte and natural killer cells in advanced breast cancer patients. Complement Ther Med. 2013;21(6):689–695.
38. Baldwin DS, Anderson IM, Nutt DJ, et al. Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder. Br J Psychiatry. 2005;186:1–2.
39. Selye H. Stress and the general adaptation syndrome. Br Med J. 1950;1(4667):1383–1392.
40. Tandon N, Yadav SS. Safety and clinical effectiveness of ashwagandha (Withania somnifera) root in human ailments. J Ethnopharmacol. 2020;255:112768.
41. McEwen BS, Magarinos AM. Stress effects on morphology and function of the hippocampus. Ann NY Acad Sci. 1997;821:271–284.
42. Meerlo P, Sgoifo A, Suchecki D. Restricted and disrupted sleep: Effects on autonomic function, neuroendocrine stress systems and stress responses. Sleep Med Rev. 2008;12(3):197–210.
43. Khyati D, Shailaja R, Kavitha B, et al. Role of Ashwagandha in integrative mental health: bridging the gap between tradition and modern research. J Altern Complement Med. 2022;28(9):1232–1239.
44. Chandola T, Britton A, Brunner E, et al. Work stress and coronary heart disease: what are the mechanisms? Eur Heart J. 2008;29(5):640–648.
45. Wankhede S, Langade D, Joshi K, et al. Examining the effect of withania somnifera supplementation on muscle strength and recovery: a randomised controlled trial. J Int Soc Sports Nutr. 2015;12:43.
46. Durg S, Shivaram SB, Bavage S. Withania somnifera (ashwagandha) in animal skeletal muscle atrophy: A systematic review and meta-analysis. J Diet Suppl. 2019;16(4):442–456.
47. Dwivedi V, Anandan EM, Muthusamy R, et al. The immunostimulatory effect of ashwagandha in stress-induced animals: An overview. Pharmacogn Rev. 2014;8(15):95–101.
48. Puttick S, Toh LS, Zentek J, et al. A systematic review and meta-analysis of the efficacy of ashwagandha (Withania somnifera) in improving muscle strength and recovery. Evid Based Complement Alternat Med. 2022;2022:9534168.
49. Powers SK, Jackson MJ. Exercise-induced oxidative stress: Cellular mechanisms and impact on muscle force production. Physiol Rev. 2008;88(4):1243–1276.
50. Sethi J, Sood S, Seth S, et al. Protective effect of ashwagandha root extract on forced swimming-induced oxidative stress in mice. Pharmacogn Res. 2020;12(3):242–248.
51. Sharma AK, Basu I, Singh S. Efficacy and safety of ashwagandha root extract in subclinical hypothyroid patients: A double-blind, randomized placebo-controlled trial. J Altern Complement Med. 2018;24(3):243–248.
52. Miroddi M, Calapai G, Navarra M, et al. Systematic review of clinical trials assessing pharmacological properties of Withania somnifera (ashwagandha). Indian J Pharmacol. 2015;47(2):137–146.
53. Tandon VR. Medicinal uses and biological activities of vitex negundo. Nat Prod Rad. 2005;4(3):162–167.
54. Kulkarni AA, Sharma GK, Ghugare DS, et al. Industrial scale processing technologies for ashwagandha (Withania somnifera): A critical review. J Appl Res Med Aromat Plants. 2021;21:100286.
55. Panda AK, Kar A. Ashwagandha (Withania somnifera) and its physiological influences on the testicular functions. J Ethnopharmacol. 2022;291:115204.
56. Martino JV, Kotenko SV, Sturm A. Adaptive immune mechanisms in inflammatory bowel disease. Curr Gastroenterol Rep. 2019;21(8):36.