Cited by 306Phytochemicals and Medicinal PlantsMedicinal Plants and NeuroprotectionMedicinal Plant Research

The DOI matches its Crossref record; 368 of the 482 references it cites were found in a registry or an index; 2 of the 354 sources its claims cite were checked for support.

Withania somnifera (L.) Dunal (Ashwagandha): A comprehensive review on ethnopharmacology, pharmacotherapeutics, biomedicinal and toxicological aspects

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Abstract

Withania somnifera (L.) Dunal (Solanaceae) has been used as a traditional Rasayana herb for a long time. Traditional uses of this plant indicate its ameliorative properties against a plethora of human medical conditions, viz. hypertension, stress, diabetes, asthma, cancer etc. This review presents a comprehensive summary of the geographical distribution, traditional use, phytochemistry, and pharmacological activities of W. somnifera and its active constituents. In addition, it presents a detailed account of its presence as an active constituent in many commercial preparations with curative properties and health benefits. Clinical studies and toxicological considerations of its extracts and constituents are also elucidated. Comparative analysis of relevant in-vitro, in-vivo, and clinical investigations indicated potent bioactivity of W. somnifera extracts and phytochemicals as anti-cancer, anti-inflammatory, apoptotic, immunomodulatory, antimicrobial, anti-diabetic, hepatoprotective, hypoglycaemic, hypolipidemic, cardio-protective and spermatogenic agents. W. somnifera was found to be especially active against many neurological and psychological conditions like Parkinson's disease, Alzheimer's disease, Huntington's disease, ischemic stroke, sleep deprivation, amyotrophic lateral sclerosis, attention deficit hyperactivity disorder, bipolar disorder, anxiety, depression, schizophrenia and obsessive-compulsive disorder. The probable mechanism of action that imparts the pharmacological potential has also been explored. However, in-depth studies are needed on the clinical use of W. somnifera against human diseases. Besides, detailed toxicological analysis is also to be performed for its safe and efficacious use in preclinical and clinical studies and as a health-promoting herb.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This review synthesizes ethnopharmacology, phytochemistry, pharmacotherapeutics, clinical and toxicological data on *Withania somnifera* (Ashwagandha), reporting a wide range of bioactive constituents and pharmacological activities. It concludes that WS has broad therapeutic potential, but many findings remain preclinical or in silico and require clinical validation.

Key findings

  • Phytochemically, the review reports more than 12 alkaloids, 40 withanolides, and several sitoindosides in WS, with withanolide D and withaferin A as dominant withanolides; organ-specific distributions are summarized for roots, leaves, and fruits.
  • Preclinical studies report anti-cancer/apoptotic, anti-inflammatory, immunomodulatory, anti-diabetic, cardioprotective, antimicrobial, neuroprotective, and sleep/anxiolytic/antistress activities. Examples include a novel root protein fraction with IC50 92 µg/ml in MDA-MB-231 cells, methanolic root extract with IC50 10 µg/ml in PC3 cells, and anti-*Salmonella typhimurium* activity with a 32.00 ± 0.75 mm zone of inhibition and MIC 6.25 mg/ml.
  • Clinical reports include 240 mg Shoden daily reducing HAM-A, DASS-21, morning cortisol, and DHEA; 300 mg twice daily standardized to 1.5% withanolides improving mental health, concentration, vitality, and social function; 3 g/day root powder stabilizing blood glucose comparably to Daonil; and 300 mg capsule for 60 days reducing serum cortisol.
  • Toxicity data include LD50 of total root alkaloids at 465 mg/kg in rats and 432 mg/kg in mice, alcoholic root extract LD50 1260 mg/kg in mice, withaferin A i.p. LD50 around 80 mg/kg in mice, and no toxicity up to 3000 mg/kg for a withanolide-free aqueous root fraction.

Methods

  • Narrative comprehensive review covering ethnopharmacology, phytochemistry, pharmacotherapeutics, clinical studies, and toxicology; no systematic review protocol or meta-analysis is stated.
  • Data sources include ethnomedicinal reports, Ayurvedic and herbal commercial formulations, phytochemical isolation studies, preclinical in vitro and in vivo experiments, clinical trials, and toxicity studies.
  • Main analysis is qualitative synthesis, with tables summarizing traditional uses, commercial formulations, major phytochemicals, organ-specific phytochemical distribution, pharmacological properties, and neuroprotective/psychoactive activities.

Limitations

  • The paper states that in silico COVID-19 findings need validation in in vitro and in vivo systems, that no approved anti-cancer drug candidates from WS are available, and that clinical trials with WS phytochemicals/formulations are needed.
  • The paper notes that one stress study lacked merit because of a small sample, and that many neuroprotective drugs effective in animal models have failed clinical trials, with no clinical drugs available for ischemic stroke.
  • Evident from the text: the review is narrative rather than systematic, and findings are heterogeneous across extracts, doses, models, and study designs, with many claims relying on preclinical or in silico evidence.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.biopha.2021.112175

Cites

368 of 368 references verified0 citation errors · 0 not checkable

Statistics

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Claims the paper makes

302 Not checked yet · 9 Own interpretation · 1 Couldn’t confirm · 1 No basis given · accuracy not yet measured

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Show all 180 claims

  • Probably not a substantial claim. 9
  • It may state two separate claims as one. 78
  • The quote only partly states this claim. 63
133 of 133
  • The paper relies on this without support.

    No approved drug candidates from Withania somnifera are available as of the time of the review.

    “Though several formulations of WS showed very promising anti-cancer activities in both in vitro and in vivo conditions, still no approved drug candidates are available till now.”
  • The paper relies on this without support.

    Withanolides are marker compounds characteristically present in Solanaceae members, especially in the Withania genus.

    “Withanolides are marker compounds as they are characteristically present in Solanaceae members, especially in the Withania genus.”
  • The paper relies on this without support.

    The dominant withanolides are withanolide D and withaferin A.

    “The dominant withanolides are withanolide D and withaferin A.”
  • The paper relies on this without support.

    The neuroprotective and other therapeutic effects of WS observed in animal models and in vitro studies will translate to humans.

    “was suggested as a promising therapeutic agent against TDP-43 proteinopathy [96].”
    “In a randomized, double-blind, placebo-controlled study among 66 patients, a standardized extract of WS (WSE) was suggested as a promising adjunctive treatment in patients affected by recent exacerbations of schizophrenia [71].”
  • The paper relies on this without support.

    Some drugs for neurodegenerative disease have side effects.

    “Besides, some of them come with side effects.”
  • The paper relies on this without support.

    Withania somnifera contains a varied range of bioactive compounds including alkaloids, steroids, flavonoids, and phenols.

    “Ashwagandha houses a varied range of bioactive compounds ranging from alkaloids to steroids, flavonoids to phenols.”
  • The paper relies on this without support.

    Withania somnifera extract has antioxidant properties.

    “The antioxidant nature of WS extract makes it very suitable for treating neurological disorders associated with oxidative burst.”
  • The paper relies on this without support.

    Withania somnifera can promote neuronal health and help restore neurodegradation.

    “Moreover, it can promote neuronal health that can help to restore neurodegradation.”
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Citations

Cites

Items 201–368 of 368

Research works printed but not linked: 46

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Metadata

Authors
Paul, S., Chakraborty, S., Anand, U., Dey, S., Nandy, S., Ghorai, M., Saha, S. C., Patil, M. T., Kandimalla, R., Proćków, J., & Dey, A.
Affiliations
  • Presidency University (IN)
  • Ben-Gurion University of the Negev (IL)
  • University of Calcutta (IN)
  • University of Kalyani (IN)
  • Savitribai Phule Pune University (IN)
  • Kakatiya Medical College (IN)
  • Wrocław University of Environmental and Life Sciences (PL)
Corresponding author
  • Proćków, Jarosław
  • Dey, Abhijit
Venue
Biomedicine & Pharmacotherapy
Publisher
Elsevier BV
Published
2021-11
Volume
143
Pages
112175
ISSN
0753-3322 (ISSN-L)
OpenAlex
W3202927745
Cited by
306
References
482
Citations by year
2026: 67 · 2025: 70 · 2024: 82 · 2023: 51 · 2022: 33 · 2021: 3
FWCI
9.70
Type
journal article
Language
en
Open access
Locations
  • Biomedicine & Pharmacotherapy (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Presidency University
Topics
  • Health Sciences › Medicine › Complementary and alternative medicine › Phytochemicals and Medicinal Plants
  • Health Sciences › Medicine › Complementary and alternative medicine › Medicinal Plants and Neuroprotection
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Medicinal Plant Research
Keywords
Withania somnifera, ethnopharmacology, Rasayana, phytochemistry, pharmacological activity, anticancer activity, anti-inflammatory activity, neuroprotective activity, hepatoprotection, antidiabetic activity, immunomodulation, antimicrobial activity, toxicity, traditional medicine, Parkinson's disease, Alzheimer's disease, anxiety and depression
MeSH terms
COVID-19, SARS-CoV-2, COVID-19 Drug Treatment, Animals, Antiviral Agents, Humans, Plant Extracts, Psychotropic Drugs, Plant Roots, Risk Assessment, Neuroprotective Agents, Ethnopharmacology, Withania, Patient Safety, Phytochemicals

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