Published: 2016-12-30

Evaluation of effect of highly standardized aqueous extract of roots and leaves of Withania somnifera on cold pressor test induced cardiovascular changes in healthy human subjects

Raveendranath Pilli, Niranjan Koilagundla, Ramakanth GSH, Usharani Pingali


Background: Stress is an important cardiovascular risk factor. Cold pressor test (CPT) is a simple, validated, non-invasive test used to measure stress induced changes in cardiovascular parameters. The objective of this study was to evaluate effect of Withania somnifera extract on cold pressor stress test induced changes on cardiovascular parameters and aortic wave reflections in healthy human subjects.

Methods: This was a double-blind, placebo controlled, crossover study. Participants were randomized to receive either two capsules of Withania somnifera extract 250 mg or two capsules of placebo twice daily for 14 days. Pharmacodynamic parameters heart rate, aortic pressure, augmentation index (AIx), subendocardial viability ratio (SEVR), radial and aortic blood pressure (BP) were recorded before and after CPT at baseline and at end of treatment. After washout period of 10 days, subjects crossed over to other treatment group and same procedure was repeated. Safety assessments were done at baseline and at end of treatment.

Results: A total of 20 volunteers completed the study. Compared with baseline and placebo, Withania somnifera extract produced a significant decrease in mean percent change of arterial stiffness indices (AIx, radial and aortic BP). SEVR with CPT increased, however it was non-significant compared to baseline and placebo. Both treatments were well-tolerated and no serious adverse events were reported.

Conclusions: Withania somnifera extract showed a significant decrease in cold pressor stress test induced changes on aortic wave reflections, suggesting its beneficial effects in reducing stress induced cardiovascular changes. However, further clinical studies are warranted to evaluate these effects in patients with cardiovascular and other associated diseases.


Augmentation index, Cardiovascular disease, Cold pressor test, Withania somnifera

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Bernard C. An introduction to the study of experimental medicine. Transl. HC Greene. New York: Collier; 18651961.

Cannon WB. Bodily changes in pain, hunger, fear and rage. 2nd ed. New York: Appleton; 1929.

Selye H. The stress of life. New York: McGraw-Hill; 1956.

Esch T, Stefano GB, Fricchione GL, Benson H. An overview of stress and its impact in immunological diseases. Modern Aspects of Immunobiology, 2002;2(4):187-92.

Negrao AB, Deuster PA, Gold PW, Singh A, Chrousos GP. Individual reactivity and physiology of the stress response. Biomedical Pharmacother. 2000;54:122-8.

McCarty R, Gold P. Catecholamines, stress, and disease: a psychobiological Perspective. Psychosomatic Medicine. 1996;58:590-7.

Newlin DB, Levenson RW. Cardiovascular responses of individuals with type A behavior pattern and parental coronary heart disease. Journal of Psychosomatic Research. 1982;26:393-402.

Marchi ED, Baldassari F, Bononi A, Wieckowski MR, Pinton P. Oxidative stress in cardiovascular diseases and obesity. Role of p66Shc and Protein Kinase C. Oxidative Medicine and Cellular Longevity. 2013: Article ID 564961:11.

Dhalla NS, Temsah RM, Netticadan T. Role of oxidative stress in cardiovascular diseases. J Hypertens. 2000;18(6):655-73.

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.

Uddin Q, Samiulla L, Singh VK, Jamil SS. Phytochemical and pharmacological profile of Withania somnifera dunal: a review. Journal of Applied Pharmaceutical Science. 2012;02 (01):170-5.

Mohanty I, Arya DS, Dinda A, Talwar KK, Joshi S, Gupta SK. Mechanisms of cardio protective effect of Withania somnifera in experimentally induced myocardial infarction. Basic Clin Pharmacol Toxicol. 2004;94(4):184-90.

Komulainen S, Rintamaki H, Virokannas H, Kiukaanniemi SK. Blood pressure responses to whole-body cold exposure: effect of metoprolol. J Hum Hypertens. 2004;18:905-906.

Korhonen M. Helping inuit clients: cultural relevance and effective counselling. Int J Circumpolar Health. 2004;63:135-8.

Bamett PH, Hines EA, Schirger A, Gage RP. Blood pressure and vascular reactivity to the cold pressor test: restudy of 207 subjects 27 years later. JAMA 1963;183:845-8.

Reddy KS, Rani PU, Naidu MU, Rao TR. A simple cold pressure technique for the evaluation of analgesic drugs in healthy subjects. Indian J Pharmacol. 2012;44:571-5.

Karamanoglu M, O’Rourke MF, Avolio AP, Kelly RP. An analysis of the relationship between central aortic and peripheral upper limb pressure waves in man. Eur Heart J. 1993;14:160-7.

Chen CH, Nevo E, Fetics B, Pak PH, Yin FC, Maughan WL, et al. Estimation of central aortic pressure waveform by mathematical transformation of radial tonometry pressure. Validation of generalized transfer function. Circulation. 1997;95:1827-36.

Vlachopoulos C, Hirata K, O’Rourke MF. Effect of caffeine on aortic elastic properties and wave reflection. J Hypertens. 2003;21:563-70.

Doonan RJ, Scheffler P, Yu A, Egiziano G, Mutter A, Bacon S, et al. Altered arterial stiffness and sub endocardial viability ratio in young healthy light smokers after acute exercise. PLoS One. 2011;6:26151.

Lin WH, Zhang H, Zhang YT. Investigation on cardiovascular risk prediction using physiological parameters. Computational and Mathematical Methods in Medicine. 2013;Article ID 272691:21.

Mitchell GF. Arterial stiffness and wave reflection: biomarkers of cardiovascular risk. Artery Res. 2009;3:56-64.

Lafleche AB, Pannier BM, Lalous B, Safar ME. Arterial response during cold pressor test in border-line hypertension. Am J Physiol.1998;275:409-15.

Mourot L, Bouhaddi M, Regnard J. Effects of the cold pressor test on cardiac autonomic control in normal subjects. Physiol Res. 2009;58(1):83-91.

Silverthorn DU, Michael J. Cold stress and the cold pressor test. Advances in Physiology Education Published. 2013;37(1|):93-6.

Schwabe L, Haddad L, Schachinger H. HPA axis activation by a socially evaluated cold-pressor test. Psycho neuro endocrinology. 2008;33:890-5.

Edwards DG, Roy MS, Prasad RY. Wave reflection augments central systolic and pulse pressures during facial cooling. Am J Physiol Heart Circ Physiol. 2008;294:2535-9.

Tapas P, Regmi P, Adhikari P, Roychowdhury P. Cold pressor test as a predictor of hypertension. J Tehran Univ Heart Cent. 2009;3:177-80.

Mitchell GF, Lacourcière Y, Arnold JMO, Dunlap ME, Conlin PR, Izzo JL, et al. Changes in aortic stiffness and augmentation index after acute converting enzyme or vasopeptidase inhibition. Hypertension. 2005;46:1111-7.

Budhiraja RD, Sudhir SJ. Sci Ind Res. 1987;42:488-91.

Glotter E, Kirson I, Abraham A, Lavie D. Tetrahedron. 1973;29:1353-64.

Malhotra CL, Das PK, Dhalla NS, Prasad K. Studies on Withania ashwagandha, kaul III. The effect of total alkaloids on the cardiovascular system and respiration. Indian J Med Res. 1981;49:448-60.

Dhalla NS, Temsah RM, Netticadan T. Role of oxidative stress in cardiovascular diseases. J Hypertens. 2000;18(6):655-73.

Alam N, Hossain M, Khalil MI, Moniruzzaman M, Sulaiman SA, Gan SH, et al. Recent advances in elucidating the biological properties of Withania somnifera and its potential role in health benefits. Phytochem Rev. 2012;11:97-112.

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;94:184-90.

Gupta SK, Mohanty I, Talwar KK, Dinda A, Joshi S, Bansal P, et al. Cardioprotection from ischemia and reperfusion injury by Withania somnifera: a hemodynamic, biochemical and histopathological assessment. Mol. Cell Biochem. 2004;260:39-47.

Thirunavukkarasu M, Penumathsa S, Juhasz B, Zhan L, Bagchi M, Yasmin T, et al. Enhanced cardiovascular function and energy level by a novel chromium (III)-supplement. Biofactors. 2006;27:53-67.

Prince PSM, Selvaraju S, Devika PT, Vaithianathan. Cardioprotective effect of ‘Marutham’ a polyherbal formulation on isoproterenol induced myocardial infarction in Wistar rats. Fitoterapia. 2008;79:433-8.

Sharma V, Sharma S, Pracheta, Paliwal R. Withania somnifera: a rejuvenating ayurvedic medicinal herb for the treatment of various human ailments. IJPRIF. 2011;3(1):187-92.