Withania somnifera (L.) Dunal (Ashwagandha): A Narrative Review of Phytochemistry, Standardization, Pharmacology, Bioavailability and Safety
Ashwagandha: A Narrative Review
DOI:
https://doi.org/10.61280/gpxtnt05Keywords:
Withania somnifera, Ashwagandha, Withanolides, Withaferin A, Standardization, HPLC, Adaptogen, Herb-induced liver injuryAbstract
Background: Withania somnifera (L.) Dunal (Ashwagandha) is a major Rasayana herb of Indian medicine and a widely marketed dietary supplement, yet inconsistent extract quality and emerging safety signals limit its translation. This review integrates current evidence on its phytochemistry, standardization, pharmacology, bioavailability and safety.
Methods: A narrative review of PubMed literature searched in October 2026, prioritizing systematic reviews, randomized trials, validated analytical studies, pharmacokinetic studies and safety reports; 27 records were included.
Results: The bioactive profile is dominated by withanolides (withaferin A, withanolide A, withanoside IV) and alkaloids. High-performance thin-layer chromatography (HPTLC), high-performance liquid chromatography (HPLC) and liquid chromatography–tandem mass spectrometry (LC–MS/MS) methods now quantify marker withanolides in extracts, Ayurvedic formulations and plasma. Meta-analyses of randomized trials report modest reductions in perceived stress, anxiety and serum cortisol and improved sleep, but heterogeneity is high and trials are small. Human pharmacokinetic studies show rapid withanolide absorption, and formulation influenced systemic exposure. Case reports and a scoping review of 25 patients describe idiosyncratic, mostly cholestatic or mixed liver injury, rarely requiring transplantation.
Conclusions: Ashwagandha is promising, but standardized and well-characterized extracts, longer trials with liver monitoring, and stronger pharmacovigilance are required before evidence-based use can be recommended.
Downloads
References
1. 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. Biomed Pharmacother. 2021;143:112175. doi:10.1016/j.biopha.2021.112175
2. Mandlik Ingawale DS, Namdeo AG. Pharmacological evaluation of Ashwagandha highlighting its healthcare claims, safety, and toxicity aspects. J Diet Suppl. 2021;18(2):183-226. doi:10.1080/19390211.2020.1741484
3. Speers AB, Cabey KA, Soumyanath A, Wright KM. Effects of Withania somnifera (Ashwagandha) on stress and the stress-related neuropsychiatric disorders anxiety, depression, and insomnia. Curr Neuropharmacol. 2021;19(9):1468-95. doi:10.2174/1570159X19666210712151556
4. Wiciński M, Fajkiel-Madajczyk A, Kurant Z, Kurant D, Gryczka K, Falkowski M, et al. Can Ashwagandha benefit the endocrine system? A review. Int J Mol Sci. 2023;24(22):16513. doi:10.3390/ijms242216513
5. Bokan G, Glamočanin T, Mavija Z, Vidović B, Stojanović A, Björnsson ES, et al. Herb-induced liver injury by Ayurvedic Ashwagandha as assessed for causality by the updated RUCAM: an emerging cause. Pharmaceuticals (Basel). 2023;16(8):1129. doi:10.3390/ph16081129
6. McIntyre D, Nguyen P, Kim Y, Meyer B, Salloum M. Ashwagandha (Withania somnifera)-associated liver injury: a scoping review of clinical characteristics and safety considerations. Cureus. 2026;18(5):e109764. doi:10.7759/cureus.109764
7. Vaidya VG, Naik NN, Ganu G, Parmar V, Jagtap S, Saste G, et al. Clinical pharmacokinetic evaluation of Withania somnifera (L.) Dunal root extract in healthy human volunteers: a non-randomized, single dose study utilizing UHPLC-MS/MS analysis. J Ethnopharmacol. 2024;322:117603. doi:10.1016/j.jep.2023.117603
8. Tancreda G, Ravera S, Panfoli I. Preclinical evidence of Withania somnifera and Cordyceps spp.: neuroprotective properties for the management of Alzheimer’s disease. Int J Mol Sci. 2025;26(11):5403. doi:10.3390/ijms26115403
9. Meena AK, Rekha P, Perumal A, Gokul M, Swathi KN, Ilavarasan R. Estimation of Withaferin-A by HPLC and standardization of the Ashwagandhadi lehyam formulation. Heliyon. 2021;7(2):e06116. doi:10.1016/j.heliyon.2021.e06116
10. Wang F, Zhao J, Bai J, Gao K, Cui D, Chen Y, et al. Liquid chromatography-tandem mass spectrometry to assess the pharmacokinetics and tissue distribution of withaferin A in rats. J Chromatogr B Analyt Technol Biomed Life Sci. 2019;1122-1123:90-5. doi:10.1016/j.jchromb.2019.05.016
11. Halegoua-DeMarzio D, Navarro V. Challenges in herbal-induced liver injury identification and prevention. Liver Int. 2025;45(3):e16071. doi:10.1111/liv.16071
12. Choudhary S, Kaur IP, Malik J. Development and validation of a novel, rapid gradient HPLC method for simultaneous estimation of bioactive marker compounds in a mixture of Convolvulus pluricaulis, Withania somnifera and Bacopa monnieri extracts. J Chromatogr Sci. 2019;57(10):920-30. doi:10.1093/chromsci/bmz075
13. Ali A, Maher S, Khan SA, Chaudhary MI, Musharraf SG. Sensitive quantification of six steroidal lactones in Withania coagulans extract by UHPLC electrospray tandem mass spectrometry. Steroids. 2015;104:176-81. doi:10.1016/j.steroids.2015.09.011
14. Ramapalaniappan A, Loganathan V, Morde A, Padigaru M, Patni P, Joshua L, et al. Superior bioavailability of a novel 1.5% Ashwagandha formulation (Zenroot): a randomized, double-blind, single-dose, comparative, oral bioavailability study in healthy adults. Adv Ther. 2025;42(10):4964-76. doi:10.1007/s12325-025-03292-7
15. Arumugam V, Vijayakumar V, Balakrishnan A, Bhandari RB, Boopalan D, Ponnurangam R, et al. Effects of Ashwagandha (Withania somnifera) on stress and anxiety: a systematic review and meta-analysis. Explore (NY). 2024;20(6):103062. doi:10.1016/j.explore.2024.103062
16. Fatima K, Malik J, Muskan F, Raza G, Waseem A, Shahid H, et al. Safety and efficacy of Withania somnifera for anxiety and insomnia: systematic review and meta-analysis. Hum Psychopharmacol. 2024;39(6):e2911. doi:10.1002/hup.2911
17. Cheah KL, Norhayati MN, Husniati Yaacob L, Abdul Rahman R. Effect of Ashwagandha (Withania somnifera) extract on sleep: a systematic review and meta-analysis. PLoS One. 2021;16(9):e0257843. doi:10.1371/journal.pone.0257843
18. Zhang W, Yan Y, Wu Y, Yang H, Zhu P, Yan F, et al. Medicinal herbs for the treatment of anxiety: a systematic review and network meta-analysis. Pharmacol Res. 2022;179:106204. doi:10.1016/j.phrs.2022.106204
19. Lorca C, Mulet M, Arévalo-Caro C, Sánchez MÁ, Perez A, Perrino M, et al. Plant-derived nootropics and human cognition: a systematic review. Crit Rev Food Sci Nutr. 2023;63(22):5521-45. doi:10.1080/10408398.2021.2021137
20. Dube K, Stoinescu A, Sadler J, Truong M, Malakoti-Negad N, Chaudhry M, et al. Multidimensional neuroprotective effects of combined Ubisol-Q10 and Ashwagandha (Withania somnifera) in male and female 5XFAD mice. Nutrients. 2026;18(19):3270. doi:10.3390/nu18193270
21. Nimbalkar J, Shinde R. Plant-derived phytochemicals for Alzheimer’s disease: mechanisms of action, experimental evidence, and therapeutic perspectives. J Nat Med. Published online October 8, 2026. doi:10.1007/s11418-026-02090-x
22. Loureiro MRC, Fernandes JP, Paranhos A. Plant-derived bioactive compounds in schizophrenia: pharmacological mechanisms and emerging drug targets. Curr Drug Targets. Published online September 29, 2026. doi:10.2174/0113894501514494260916073129
23. Sah AK, Das J, Umarovich AI, Agarwal S, Prabhakar PK, Vashishtha A, et al. Targeting cancer stem cells with phytochemicals: molecular mechanisms and therapeutic potential. Biomedicines. 2026;14(1):215. doi:10.3390/biomedicines14010215
24. Muttiah B, Abdullah NAH. Natural compounds in ovarian cancer: mechanistic insights and therapeutic potential. Front Pharmacol. 2026;16:1687805. doi:10.3389/fphar.2025.1687805
25. Nagaraja H, Nidhi MKJ, Ganesh A, Shivaraj H, Uma Reddy B. Bio-templated synthesis of crystalline nanocellulose/MgO hybrids from Withania somnifera: for selective anticancer, antioxidant, and anti-inflammatory activity. Bioorg Chem. 2026;183:110593. doi:10.1016/j.bioorg.2026.110593
26. Philips CA, Theruvath AH. A comprehensive review on the hepatotoxicity of herbs used in the Indian (Ayush) systems of alternative medicine. Medicine (Baltimore). 2024;103(16):e37903. doi:10.1097/MD.0000000000037903
27. Koturbash I, Yeager RP, Mitchell CA, Ferguson S, Navarro VJ, Paine MF, et al. Botanical-induced toxicity: liver injury and botanical-drug interactions. A report on a Society of Toxicology Annual Meeting symposium. Regul Toxicol Pharmacol. 2024;153:105708. doi:10.1016/j.yrtph.2024.105708
Downloads
Published
Issue
Section
License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
