Foods and Raw Materials Foods and Raw Materials Foods and Raw Materials 2308-4057 2310-9599 76145 10.21603/2308-4057-2025-1-622 Review Article Review Article Review Article Immunomodulatory effect of ashwagandha (Withania somnifera(L.) Dunal) and its impact on COVID-19 Immunomodulatory effect of ashwagandha (Withania somnifera(L.) Dunal) and its impact on COVID-19 https://orcid.org/0009-0003-4809-6363 Pushpakaran Arun M. K. Pushpakaran Arun M. K. https://orcid.org/0000-0003-0838-6393 Singh Jyoti Singh Jyoti jyotisingh9377@gmail.com https://orcid.org/0000-0002-5807-4091 Rasane Prasad Rasane Prasad https://orcid.org/0000-0002-4500-1053 Kaur Sawinder Kaur Sawinder https://orcid.org/0000-0003-3718-5734 Kaur Jaspreet Kaur Jaspreet https://orcid.org/0000-0001-7196-7524 Kaur Jasjit Kaur Jasjit https://orcid.org/0000-0002-0550-262X Kumar Mukul Kumar Mukul https://orcid.org/0000-0002-4013-3516 Assouguem Amine Assouguem Amine Lovely Professional University Phagwāra Индия Lovely Professional University Phagwāra India Lovely Professional University Phagwara Индия Lovely Professional University Phagwara India Lovely Professional University Phagwāra Индия Lovely Professional University Phagwāra India Lovely Professional University Phagwara Индия Lovely Professional University Phagwara India Lovely Professional University Phagwara Индия Lovely Professional University Phagwara India Lovely Professional University Phagwāra Индия Lovely Professional University Phagwāra India Lovely Professional University Phagwāra Индия Lovely Professional University Phagwāra India Sidi Mohamed Ben Abdellah University Fes Марокко Sidi Mohamed Ben Abdellah University Fes Morocco 07 11 2024 07 11 2024 13 1 46 57 11 04 2023 06 06 2023 https://jfrm.ru/en/issues/22431/22447/

Ashwagandha (Withania somnifera(L.) Dunal) is an Ayurvedic medicinal herb that has been known for its therapeutic properties for millennia. Ashwagandha contains several bioactive compounds, including withanolides, alkaloids, and saponins. They make ashwagandha a potent adaptogen and a versatile herb that can maintain optimal health and overall well-being. Ashwagandha reduces stress and anxiety, as well as boosts the immune system. Its anti-inflammatory properties treat arthritis, asthma, diabetes, and inflammatory bowel disease. Ashwagandha produces an immunomodulatory effect on natural killer cells, lymphocytes, and leukemia cells. It enhances the activity of natural killer cells, increases lymphocyte function, and induces apoptosis in leukemia cells. However, its mechanism of action still remains understudied. Ashwagandha has an impact on COVID-19: phytochemical withanone blocks or weakens the interaction between S-protein and Angiotensin-converting enzyme 2. Withanoside V and somniferine inhibit viral transcription and replication caused by SARSCoV-2 Mpro. This review explores the potential utilization of ashwagandha in the food industry, i.e., its safety and toxicity, as well as the mechanism behind its immunomodulatory effect.

Ashwagandha (Withania somnifera(L.) Dunal) is an Ayurvedic medicinal herb that has been known for its therapeutic properties for millennia. Ashwagandha contains several bioactive compounds, including withanolides, alkaloids, and saponins. They make ashwagandha a potent adaptogen and a versatile herb that can maintain optimal health and overall well-being. Ashwagandha reduces stress and anxiety, as well as boosts the immune system. Its anti-inflammatory properties treat arthritis, asthma, diabetes, and inflammatory bowel disease. Ashwagandha produces an immunomodulatory effect on natural killer cells, lymphocytes, and leukemia cells. It enhances the activity of natural killer cells, increases lymphocyte function, and induces apoptosis in leukemia cells. However, its mechanism of action still remains understudied. Ashwagandha has an impact on COVID-19: phytochemical withanone blocks or weakens the interaction between S-protein and Angiotensin-converting enzyme 2. Withanoside V and somniferine inhibit viral transcription and replication caused by SARSCoV-2 Mpro. This review explores the potential utilization of ashwagandha in the food industry, i.e., its safety and toxicity, as well as the mechanism behind its immunomodulatory effect.

 Ashwagandha immunity lymphocytes natural killer cells cancer COVID-19 Ashwagandha immunity lymphocytes natural killer cells cancer COVID-19

Amritha N, Bhooma V, Parani M. Authentication of the market samples of Ashwagandha by DNA barcoding reveals that powders are significantly more adulterated than roots. Journal of Ethnopharmacology. 2020;256. https://doi.org/10.1016/j.jep.2020.112725 Amritha N, Bhooma V, Parani M. Authentication of the market samples of Ashwagandha by DNA barcoding reveals that powders are significantly more adulterated than roots. Journal of Ethnopharmacology. 2020;256. https://doi.org/10.1016/j.jep.2020.112725 Bonilla DA, Moreno Y, Gho C, Petro JL, Odriozola-Martínez A, Kreider RB. Effects of Ashwagandha (Withania somnifera) on physical performance: Systematic review and bayesian meta-analysis. Journal of Functional Morphology and Kinesiology. 2021;6(1). https://doi.org/10.3390/jfmk6010020 Bonilla DA, Moreno Y, Gho C, Petro JL, Odriozola-Martínez A, Kreider RB. Effects of Ashwagandha (Withania somnifera) on physical performance: Systematic review and bayesian meta-analysis. Journal of Functional Morphology and Kinesiology. 2021;6(1). https://doi.org/10.3390/jfmk6010020 Wal A, Wal P, Rai AK, Tiwari R, Prajapati SK. Adaptogens with a special emphasis on Withania somnifera and Rhodiola rosea. In: Bagchi D, Nair S, Sen CK, editors. Nutrition and enhanced sports performance. Muscle building, endurance, and strength. Academic Press; 2019. pp. 407–418. https://doi.org/10.1016/B978-0-12-813922-6.00034-5 Wal A, Wal P, Rai AK, Tiwari R, Prajapati SK. Adaptogens with a special emphasis on Withania somnifera and Rhodiola rosea. In: Bagchi D, Nair S, Sen CK, editors. Nutrition and enhanced sports performance. Muscle building, endurance, and strength. Academic Press; 2019. pp. 407–418. https://doi.org/10.1016/B978-0-12-813922-6.00034-5 Mahato A, Chakraborty I, Baidya BK. Preparation and evaluation of fruit candy from unripe mango. International Journal of Chemical Studies. 2020;8(1):2727–2731. https://doi.org/10.22271/chemi.2020.v8.i1ao.8682 Mahato A, Chakraborty I, Baidya BK. Preparation and evaluation of fruit candy from unripe mango. International Journal of Chemical Studies. 2020;8(1):2727–2731. https://doi.org/10.22271/chemi.2020.v8.i1ao.8682 Moharana D, Bahadur V, Rout S, Prusty AK, Sahoo RK. Ashwagandha: The miracle ginseng. Food and Scientific Reports. 2020;1(10):37–42. Moharana D, Bahadur V, Rout S, Prusty AK, Sahoo RK. Ashwagandha: The miracle ginseng. Food and Scientific Reports. 2020;1(10):37–42. Paul S, Chakraborty S, Anand U, Dey S, Nandy S, Ghorai M, et al. Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects. Biomedicine and Pharmacotherapy. 2021;143. https://doi.org/10.1016/j.biopha.2021.112175 Paul S, Chakraborty S, Anand U, Dey S, Nandy S, Ghorai M, et al. Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects. Biomedicine and Pharmacotherapy. 2021;143. https://doi.org/10.1016/j.biopha.2021.112175 Bharti VK, Malik JK, Gupta RC. Ashwagandha: Multiple health benefits. In: Gupta RC, editor. Nutraceuticals. Efficacy, safety and toxicity. Academic Press; 2016. pp. 717–733. https://doi.org/10.1016/B978-0-12-802147-7.00052-8 Bharti VK, Malik JK, Gupta RC. Ashwagandha: Multiple health benefits. In: Gupta RC, editor. Nutraceuticals. Efficacy, safety and toxicity. Academic Press; 2016. pp. 717–733. https://doi.org/10.1016/B978-0-12-802147-7.00052-8 Zahiruddin S, Basist P, Parveen A, Parveen R, Khan W, Gaurav, et al. Ashwagandha in brain disorders: A review of recent developments. Journal of Ethnopharmacology. 2020;257. https://doi.org/10.1016/j.jep.2020.112876 Zahiruddin S, Basist P, Parveen A, Parveen R, Khan W, Gaurav, et al. Ashwagandha in brain disorders: A review of recent developments. Journal of Ethnopharmacology. 2020;257. https://doi.org/10.1016/j.jep.2020.112876 Bhatt N. Drug discovery from Ayurveda: Biological advances and integrative synergies. In: Bhatt N, editors. Integrative perspectives: Ayurveda, phytopharmaceuticals and natural products. Pune: Continental Prakashan; 2020. pp. 496–512. Bhatt N. Drug discovery from Ayurveda: Biological advances and integrative synergies. In: Bhatt N, editors. Integrative perspectives: Ayurveda, phytopharmaceuticals and natural products. Pune: Continental Prakashan; 2020. pp. 496–512. Mandlik DS, Namdeo AG. Pharmacological evaluation of Ashwagandha highlighting its healthcare claims, safety, and toxicity aspects. Journal of Dietary Supplements. 2021;18(2):183–226. https://doi.org/10.1080/19390211.2020.1741484 Mandlik DS, Namdeo AG. Pharmacological evaluation of Ashwagandha highlighting its healthcare claims, safety, and toxicity aspects. Journal of Dietary Supplements. 2021;18(2):183–226. https://doi.org/10.1080/19390211.2020.1741484 John J. Therapeutic potential of Withania somnifera: A report on phyto-pharmacological properties. International Journal of Pharmaceutical Sciences and Research. 2014;5(6):2131–2148. https://doi.org/10.13040/IJPSR.0975-8232.5(6).2131-48 John J. Therapeutic potential of Withania somnifera: A report on phyto-pharmacological properties. International Journal of Pharmaceutical Sciences and Research. 2014;5(6):2131–2148. https://doi.org/10.13040/IJPSR.0975-8232.5(6).2131-48 Ageyeva NM, Khrapov AA, Shirshova AA, Chemisova LE, Ulyanovskaya EV, Сhernutskaya EA. The elemental profile of ciders made from different varieties of apples. Foods and Raw Materials. 2024;12(2):273–282. https://doi.org/10.21603/2308-4057-2024-2-604 Ageyeva NM, Khrapov AA, Shirshova AA, Chemisova LE, Ulyanovskaya EV, Chernutskaya EA. The elemental profile of ciders made from different varieties of apples. Foods and Raw Materials. 2024;12(2):273–282. https://doi.org/10.21603/2308-4057-2024-2-604 Ojileh PC, Okechukwu QN. Value-added zobo drink with date juice. Food Processing: Techniques and Technology. 2023;53(3):545–553. https://doi.org/10.21603/2074-9414-2023-3-2453 Ojileh PC, Okechukwu QN. Value-added zobo drink with date juice. Food Processing: Techniques and Technology. 2023;53(3):545–553. https://doi.org/10.21603/2074-9414-2023-3-2453 Gaurav N, Kumar A, Tyagi M, Kumar D, Chauhan UK, Singh AP. Morphology of Withania somnifera (distribution, morphology, phytosociology of Withania somnifera L. Dunal). International Journal of Current Science Research. 2015;1(7):164–173. Gaurav N, Kumar A, Tyagi M, Kumar D, Chauhan UK, Singh AP. Morphology of Withania somnifera (distribution, morphology, phytosociology of Withania somnifera L. Dunal). International Journal of Current Science Research. 2015;1(7):164–173. Meher SK, Das B, Panda P, Bhuyan GC, Rao MM. Uses of Withania somnifera (Linn) Dunal (Ashwagandha) in Ayurveda and its pharmacological evidences. Research Journal of Pharmacology and Pharmacodynamics. 2016;8(1):23–29. https://doi.org/10.5958/2321-5836.2016.00006.9 Meher SK, Das B, Panda P, Bhuyan GC, Rao MM. Uses of Withania somnifera (Linn) Dunal (Ashwagandha) in Ayurveda and its pharmacological evidences. Research Journal of Pharmacology and Pharmacodynamics. 2016;8(1):23–29. https://doi.org/10.5958/2321-5836.2016.00006.9 Nile SH, Nile A, Gansukh E, Baskar V, Kai G. Subcritical water extraction of withanosides and withanolides from ashwagandha (Withania somnifera L) and their biological activities. Food and Chemical Toxicology. 2019;132. https://doi.org/10.1016/j.fct.2019.110659 Nile SH, Nile A, Gansukh E, Baskar V, Kai G. Subcritical water extraction of withanosides and withanolides from ashwagandha (Withania somnifera L) and their biological activities. Food and Chemical Toxicology. 2019;132. https://doi.org/10.1016/j.fct.2019.110659 Shah N, Singh R, Sarangi U, Saxena N, Chaudhary A, Kaur G, et al. Combinations of Ashwagandha leaf extracts protect brain-derived cells against oxidative stress and induce differentiation. PLoS ONE. 2015;10(3). https://doi.org/10.1371/journal.pone.0120554 Shah N, Singh R, Sarangi U, Saxena N, Chaudhary A, Kaur G, et al. Combinations of Ashwagandha leaf extracts protect brain-derived cells against oxidative stress and induce differentiation. PLoS ONE. 2015;10(3). https://doi.org/10.1371/journal.pone.0120554 Maurya SP, Das BK, Singh R, Tyagi S. Effect of Withania somnifer on CD38 expression on CD8+ T lymphocytes among patients of HIV infection. Clinical Immunology. 2019;203:122–124. https://doi.org/10.1016/j.clim.2019.04.003 Maurya SP, Das BK, Singh R, Tyagi S. Effect of Withania somnifer on CD38 expression on CD8+ T lymphocytes among patients of HIV infection. Clinical Immunology. 2019;203:122–124. https://doi.org/10.1016/j.clim.2019.04.003 Oza VP, Parmar PP, Kumar S, Subramanian RB. Anticancer properties of highly purified L-asparaginase from Withania somnifera L. against acute lymphoblastic leukemia. Applied Biochemistry and Biotechnology. 2010;160:1833–1840. https://doi.org/10.1007/s12010-009-8667-z Oza VP, Parmar PP, Kumar S, Subramanian RB. Anticancer properties of highly purified L-asparaginase from Withania somnifera L. against acute lymphoblastic leukemia. Applied Biochemistry and Biotechnology. 2010;160:1833–1840. https://doi.org/10.1007/s12010-009-8667-z 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. 2020. https://doi.org/10.21203/rs.3.rs-17806/v1 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. 2020. https://doi.org/10.21203/rs.3.rs-17806/v1 Shree P, Mishra P, Selvaraj C, Singh SK, Chaube R, Garg N, 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. Journal of Biomolecular Structure and Dynamics. 2022;40(1):190–203. https://doi.org/10.1080/07391102.2020.1810778 Shree P, Mishra P, Selvaraj C, Singh SK, Chaube R, Garg N, 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. Journal of Biomolecular Structure and Dynamics. 2022;40(1):190–203. https://doi.org/10.1080/07391102.2020.1810778 Marshall JS, Warrington R, Watson W, Kim HL. An introduction to immunology and immunopathology. Allergy, Asthma and Clinical Immunology. 2018;14(2). https://doi.org/10.1186/s13223-018-0278-1 Marshall JS, Warrington R, Watson W, Kim HL. An introduction to immunology and immunopathology. Allergy, Asthma and Clinical Immunology. 2018;14(2). https://doi.org/10.1186/s13223-018-0278-1 Tharakan A, Shukla H, Benny IR, Tharakan M, George L, Koshy S. Immunomodulatory effect of Withania somnifera (Ashwagandha) extract – A randomized, double-blind, placebo controlled trial with an open label extension on healthy participants. Journal of Clinical Medicine. 2021;10(16). https://doi.org/10.3390/jcm10163644 Tharakan A, Shukla H, Benny IR, Tharakan M, George L, Koshy S. Immunomodulatory effect of Withania somnifera (Ashwagandha) extract – A randomized, double-blind, placebo controlled trial with an open label extension on healthy participants. Journal of Clinical Medicine. 2021;10(16). https://doi.org/10.3390/jcm10163644 Esmaealzadeh N, Iranpanah A, Sarris J, Rahimi R. A literature review of the studies concerning selected plant-derived adaptogens and their general function in body with a focus on animal studies. Phytomedicine. 2022;105. https://doi.org/10.1016/j.phymed.2022.154354 Esmaealzadeh N, Iranpanah A, Sarris J, Rahimi R. A literature review of the studies concerning selected plant-derived adaptogens and their general function in body with a focus on animal studies. Phytomedicine. 2022;105. https://doi.org/10.1016/j.phymed.2022.154354 Sharma L. Immunomodulatory effect and supportive role of traditional herbs, spices and nutrients in management of COVID-19. 2020. https://doi.org/10.20944/preprints202009.0026.v1 Sharma L. Immunomodulatory effect and supportive role of traditional herbs, spices and nutrients in management of COVID-19. 2020. https://doi.org/10.20944/preprints202009.0026.v1 Singh B, Sharma HK, Kaur R. Storage stability of osmo-convective dried beetroot candy. Journal of Pharmacognosy and Phytochemistry. 2020;9(5):2704–2708. Singh B, Sharma HK, Kaur R. Storage stability of osmo-convective dried beetroot candy. Journal of Pharmacognosy and Phytochemistry. 2020;9(5):2704–2708. Saleem S, Muhammad G, Hussain MA, Altaf M, Bukhari SNA. Withania somnifera L.: Insights into the phytochemical profile, therapeutic potential, clinical trials, and future prospective. Iranian Journal of Basic Medical Sciences. 2020;23(12):1501–1526. https://doi.org/10.22038/ijbms.2020.44254.10378 Saleem S, Muhammad G, Hussain MA, Altaf M, Bukhari SNA. Withania somnifera L.: Insights into the phytochemical profile, therapeutic potential, clinical trials, and future prospective. Iranian Journal of Basic Medical Sciences. 2020;23(12):1501–1526. https://doi.org/10.22038/ijbms.2020.44254.10378 Mofed D, Ahmed W, Zekri A-R, Said O, Rahouma M, Faraag AHI. The antiviral efficacy of Withania somnifera (Ashwagandha) against hepatitis C virus activity: In vitro and in silico study. Advances in Microbiology. 2020;10(9):463–477. https://doi.org/10.4236/aim.2020.109035 Mofed D, Ahmed W, Zekri A-R, Said O, Rahouma M, Faraag AHI. The antiviral efficacy of Withania somnifera (Ashwagandha) against hepatitis C virus activity: In vitro and in silico study. Advances in Microbiology. 2020;10(9):463–477. https://doi.org/10.4236/aim.2020.109035 Grunz-Borgmann E, Mossine V, Fritsche K, Parrish AR. Ashwagandha attenuates TNF-α- and LPS-induced NF-κB activation and CCL2 and CCL5 gene expression in NRK-52E cells. BMC Complementary Medicine and Therapies. 2015;15. https://doi.org/10.1186/s12906-015-0958-z Grunz-Borgmann E, Mossine V, Fritsche K, Parrish AR. Ashwagandha attenuates TNF-α- and LPS-induced NF-κB activation and CCL2 and CCL5 gene expression in NRK-52E cells. BMC Complementary Medicine and Therapies. 2015;15. https://doi.org/10.1186/s12906-015-0958-z Pal A, Kumar KH, Bhushan B, Saharan V. Ashwagandha root extract inhibits acetylcholine esterase, protein modification and ameliorates H2O2-induced oxidative stress in rat lymphocytes. Pharmacognosy Journal. 2017;9(3):302–309. https://doi.org/10.5530/pj.2017.3.52 Pal A, Kumar KH, Bhushan B, Saharan V. Ashwagandha root extract inhibits acetylcholine esterase, protein modification and ameliorates H2O2-induced oxidative stress in rat lymphocytes. Pharmacognosy Journal. 2017;9(3):302–309. https://doi.org/10.5530/pj.2017.3.52 Cordo' V, van der Zwet JCG, Canté-Barrett K, Pieters R, Meijerink JPP. T-cell acute lymphoblastic leukemia: A roadmap to targeted therapies. Blood Cancer Discovery. 2021;2(1):19–31. https://doi.org/10.1158/2643-3230.BCD-20-0093 Cordo' V, van der Zwet JCG, Canté-Barrett K, Pieters R, Meijerink JPP. T-cell acute lymphoblastic leukemia: A roadmap to targeted therapies. Blood Cancer Discovery. 2021;2(1):19–31. https://doi.org/10.1158/2643-3230.BCD-20-0093 Turrini E, Calcabrini C, Sestili P, Catanzaro E, de Gianni E, Diaz AR, et al. Withania somnifera induces cytotoxic and cytostatic effects on human T leukemia cells. Toxins. 2016;8(5). https://doi.org/10.3390/toxins8050147 Turrini E, Calcabrini C, Sestili P, Catanzaro E, de Gianni E, Diaz AR, et al. Withania somnifera induces cytotoxic and cytostatic effects on human T leukemia cells. Toxins. 2016;8(5). https://doi.org/10.3390/toxins8050147 Yang J, Wang L, Guan X, Qin J-J. Inhibiting STAT3 signaling pathway by natural products for cancer prevention and therapy: In vitro and in vivo activity and mechanisms of action. Pharmacological Research. 2022;182. https://doi.org/10.1016/j.phrs.2022.106357 Yang J, Wang L, Guan X, Qin J-J. Inhibiting STAT3 signaling pathway by natural products for cancer prevention and therapy: In vitro and in vivo activity and mechanisms of action. Pharmacological Research. 2022;182. https://doi.org/10.1016/j.phrs.2022.106357 Cook KD, Waggoner SN, Waggoner SN, Whitmire JK. NK cells and their ability to modulate T cells during virus infections. Critical ReviewsTM in Immunology. 2014;34(5):359–388. https://doi.org/10.1615/CritRevImmunol.2014010604 Cook KD, Waggoner SN, Waggoner SN, Whitmire JK. NK cells and their ability to modulate T cells during virus infections. Critical ReviewsTM in Immunology. 2014;34(5):359–388. https://doi.org/10.1615/CritRevImmunol.2014010604 Ochando J, Mulder WJM, Madsen JC, Netea MG, Duivenvoorden R. Trained immunity – basic concepts and contributions to immunopathology. Nature Reviews Nephrology. 2023;19:23–37. https://doi.org/10.1038/s41581-022-00633-5 Ochando J, Mulder WJM, Madsen JC, Netea MG, Duivenvoorden R. Trained immunity – basic concepts and contributions to immunopathology. Nature Reviews Nephrology. 2023;19:23–37. https://doi.org/10.1038/s41581-022-00633-5 Trivedi MK, Jana S. In vitro evaluation of immunomodulatory effects of the test formulation by the estimation of natural killer cells and phagocytosis activities. Cell and Cellular Life Sciences Journal. 2019;4(1). https://doi.org/10.2174/1871523017666181116092934 Trivedi MK, Jana S. In vitro evaluation of immunomodulatory effects of the test formulation by the estimation of natural killer cells and phagocytosis activities. Cell and Cellular Life Sciences Journal. 2019;4(1). https://doi.org/10.2174/1871523017666181116092934 Khan MA, Ahmed RS, Chandra N, Arora VK, Ali A. In vivo, extract from Withania somnifera root ameliorates arthritis via regulation of key immune mediators of inflammation in experimental model of arthritis. Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry. 2019;18(1):55–70. https://doi.org/10.2174/1871523017666181116092934 Khan MA, Ahmed RS, Chandra N, Arora VK, Ali A. In vivo, extract from Withania somnifera root ameliorates arthritis via regulation of key immune mediators of inflammation in experimental model of arthritis. Anti-Inflammatory and Anti-Allergy Agents in Medicinal Chemistry. 2019;18(1):55–70. https://doi.org/10.2174/1871523017666181116092934 Barua A, Bradaric MJ, Bitterman P, Abramowicz JS, Sharma S, Basu S, et al. Dietary supplementation of Ashwagandha (Withania somnifera, Dunal) enhances NK cell function in ovarian tumors in the laying hen model of spontaneous ovarian cancer. American Journal of Reproductive Immunology. 2013;70(6):538–550. https://doi.org/10.1111/aji.12172 Barua A, Bradaric MJ, Bitterman P, Abramowicz JS, Sharma S, Basu S, et al. Dietary supplementation of Ashwagandha (Withania somnifera, Dunal) enhances NK cell function in ovarian tumors in the laying hen model of spontaneous ovarian cancer. American Journal of Reproductive Immunology. 2013;70(6):538–550. https://doi.org/10.1111/aji.12172 Ciotti M, Ciccozzi M, Terrinoni A, Jiang W-C, Wang C-B, Bernardini S. The COVID-19 pandemic. Critical Reviews in Clinical Laboratory Sciences. 2020;57(6):365–388. https://doi.org/10.1080/10408363.2020.1783198 Ciotti M, Ciccozzi M, Terrinoni A, Jiang W-C, Wang C-B, Bernardini S. The COVID-19 pandemic. Critical Reviews in Clinical Laboratory Sciences. 2020;57(6):365–388. https://doi.org/10.1080/10408363.2020.1783198 Fraser N, Brierley L, Dey G, Polka JK, Pálfy M, Nanni F, et al. Preprinting the COVID-19 pandemic. bioRxiv. 2020. https://doi.org/10.1101/2020.05.22.111294 Fraser N, Brierley L, Dey G, Polka JK, Pálfy M, Nanni F, et al. Preprinting the COVID-19 pandemic. bioRxiv. 2020. https://doi.org/10.1101/2020.05.22.111294 Srivastav S, Singh P, Mishra G, Jha KK, Khosa RL. Achyranthes aspera – An important medicinal plant: A review. Journal of Natural Product and Plant Resources. 2011;1(1):1–14. Srivastav S, Singh P, Mishra G, Jha KK, Khosa RL. Achyranthes aspera – An important medicinal plant: A review. Journal of Natural Product and Plant Resources. 2011;1(1):1–14. Aboyewa JA, Sibuyi NRS, Meyer M, Oguntibeju OO. Green synthesis of metallic nanoparticles using some selected medicinal plants from southern Africa and their biological applications. Plants. 2021;10(9). https://doi.org/10.3390/plants10091929 Aboyewa JA, Sibuyi NRS, Meyer M, Oguntibeju OO. Green synthesis of metallic nanoparticles using some selected medicinal plants from southern Africa and their biological applications. Plants. 2021;10(9). https://doi.org/10.3390/plants10091929 Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271–280. https://doi.org/10.1016/j.cell.2020.02.052 Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271–280. https://doi.org/10.1016/j.cell.2020.02.052 Munir M, Nadeem M, Qureshi TM, Jabbar S, Atif FA, Zeng X. Effect of protein addition on the physicochemical and sensory properties of fruit bars. Journal of Food Processing and Preservation. 2016;40(3):559–566. https://doi.org/10.1111/jfpp.12635 Munir M, Nadeem M, Qureshi TM, Jabbar S, Atif FA, Zeng X. Effect of protein addition on the physicochemical and sensory properties of fruit bars. Journal of Food Processing and Preservation. 2016;40(3):559–566. https://doi.org/10.1111/jfpp.12635 Panda AK, Kar S. Ayurvedic immuno booster: Is it myth or reality in COVID-19 pandemic. International Journal of Current Research and Review. 2021;13(1):134–140. https://doi.org/10.31782/IJCRR.2021.13140 Panda AK, Kar S. Ayurvedic immuno booster: Is it myth or reality in COVID-19 pandemic. International Journal of Current Research and Review. 2021;13(1):134–140. https://doi.org/10.31782/IJCRR.2021.13140 Sharifi-Rad J, Quispe C, Ayatollahi SA, Kobarfard F, Staniak M, Stępień A, et al. Chemical composition, biological activity, and health-promoting effects of Withania somnifera for pharma-food industry applications. Journal of Food Quality. 2021;2021. https://doi.org/10.1155/2021/8985179 Sharifi-Rad J, Quispe C, Ayatollahi SA, Kobarfard F, Staniak M, Stępień A, et al. Chemical composition, biological activity, and health-promoting effects of Withania somnifera for pharma-food industry applications. Journal of Food Quality. 2021;2021. https://doi.org/10.1155/2021/8985179 Baghel S, Saraugi SS, Kumar A, Rathore A, Soni DK. Sensory and physical evaluation of herbal biscuit incorporated with Ashwagandha (Withania somnifera) and Ragi (Eleusine coracana). International Journal of Chemical Studies. 2020;8(5):136–142. https://doi.org/10.22271/chemi.2020.v8.i5b.10290 Baghel S, Saraugi SS, Kumar A, Rathore A, Soni DK. Sensory and physical evaluation of herbal biscuit incorporated with Ashwagandha (Withania somnifera) and Ragi (Eleusine coracana). International Journal of Chemical Studies. 2020;8(5):136–142. https://doi.org/10.22271/chemi.2020.v8.i5b.10290 Abayathilaka WS, Perera GAAR, Rathnayake AMGN, Subasinghe UGPP. Developing a low-calorie green tea based ready-to-drink beverage using Brahmi (Bacopa monnieri), Ashwagandha (Withania somnifera), Stevia (Stevia rebaudiana) & Ceylon Cinnamon (Cinnamomum zeylanicum). 2021. Abayathilaka WS, Perera GAAR, Rathnayake AMGN, Subasinghe UGPP. Developing a low-calorie green tea based ready-to-drink beverage using Brahmi (Bacopa monnieri), Ashwagandha (Withania somnifera), Stevia (Stevia rebaudiana) & Ceylon Cinnamon (Cinnamomum zeylanicum). 2021. Dhole RR, Undratwad DT, Khadse PN, Meshram TA. Studies on sensory evaluation and cost structure of low-fat flavoured milk incorporated with ashwagandha (Withania somnifera) root powder. The Pharma Innovation Journal 2022;11(8):950–954. Dhole RR, Undratwad DT, Khadse PN, Meshram TA. Studies on sensory evaluation and cost structure of low-fat flavoured milk incorporated with ashwagandha (Withania somnifera) root powder. The Pharma Innovation Journal 2022;11(8):950–954. Sinha M, Mani A, Sinha P. Value addition of guava cheese cv. Allahabad safeda by medicinal herbs. Journal of Pharmacognosy and Phytochemistry. 2017;6(6):856–859. Sinha M, Mani A, Sinha P. Value addition of guava cheese cv. Allahabad safeda by medicinal herbs. Journal of Pharmacognosy and Phytochemistry. 2017;6(6):856–859. Indu PC, Awasthi P. Development and evaluation of cereal-legume based ladoo supplemented with Ashwagandha (Withania somnifera). The Pharma Innovation Journal. 2018;7(7):358–362. Indu PC, Awasthi P. Development and evaluation of cereal-legume based ladoo supplemented with Ashwagandha (Withania somnifera). The Pharma Innovation Journal. 2018;7(7):358–362. Prabu PC, Panchapakesan S, Raj CD. Acute and sub‐acute oral toxicity assessment of the hydroalcoholic extract of Withania somnifera roots in Wistar rats. Phytotherapy Research. 2013;27(8):1169–1178. https://doi.org/10.1002/ptr.4854 Prabu PC, Panchapakesan S, Raj CD. Acute and sub‐acute oral toxicity assessment of the hydroalcoholic extract of Withania somnifera roots in Wistar rats. Phytotherapy Research. 2013;27(8):1169–1178. https://doi.org/10.1002/ptr.4854 Kushwaha S, Betsy A, Chawla P. Effect of Ashwagandha (Withania somnifera) root powder supplementation in treatment of hypertension. Ethno-Medicine. 2012;6(2):111–115. https://doi.org/10.31901/24566772.2012/06.02.05 Kushwaha S, Betsy A, Chawla P. Effect of Ashwagandha (Withania somnifera) root powder supplementation in treatment of hypertension. Ethno-Medicine. 2012;6(2):111–115. https://doi.org/10.31901/24566772.2012/06.02.05 Xing D, Yoo C, Gonzalez D, Jenkins V, Nottingham K, Dickerson B, et al. Effects of acute ashwagandha ingestion on cognitive function. International Journal of Environmental Research and Public Health. 2022;19(19). https://doi.org/10.3390/ijerph191911852 Xing D, Yoo C, Gonzalez D, Jenkins V, Nottingham K, Dickerson B, et al. Effects of acute ashwagandha ingestion on cognitive function. International Journal of Environmental Research and Public Health. 2022;19(19). https://doi.org/10.3390/ijerph191911852 Lopresti AL, Smith SJ, Malvi H, Kodgule R. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. Medicine. 2019;98(37). https://doi.org/10.1097%2FMD.0000000000017186 Lopresti AL, Smith SJ, Malvi H, Kodgule R. An investigation into the stress-relieving and pharmacological actions of an ashwagandha (Withania somnifera) extract: A randomized, double-blind, placebo-controlled study. Medicine. 2019;98(37). https://doi.org/10.1097%2FMD.0000000000017186