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

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

Open access
Paul, Subhabrata, Chakraborty, Shreya, Anand, Uttpal, Dey, Swarnali, Nandy, Samapika, Ghorai, Mimosa, Saha, Suchismita Chatterjee, Patil, Manoj Tukaram +3 more·2021·Biomedicine & Pharmacotherapy
DOI 10.1016/j.biopha.2021.112175
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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.

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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

Nothing to recompute.

Claims the paper makes

0 of 354 cited sources checked · 0 supported · 0 flagged

  • Premisecitation

    Aqueous extracts of Withania somnifera (200, 400 mg/kg for 5 days) decrease blood glucose, HbA1c, and insulin levels.

    “Aqueous extracts of WS (200, 400 mg/kg for 5 days) were found to be effective in decreasing blood glucose, HbA1c, and insulin levels.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [116] Gupta, 2004, Cardioprotection from ischemia and reperfusion injury by Withania somnifera: a hemodynamic, biochemical and histopathological assessment, Mol. Cell Biochem source

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  • Premisecitation

    Withaferin-A (1.882 microg per mouse) inhibits PMA-induced EPCR shedding by inhibition of TNF-alpha and IL-1b in HUVECs by inactivating TACE.

    “Withaferin-A extracted from WS (1.882 µg per mouse) could inhibit phorbol-12-myristate 13-acetate (PMA)-induced [Endothelial protein C receptor (EPCR)] shedding by the inhibition of TNF-α and Interleukine (IL)-1b in Human Umbilical Vein Endothelial Cell lines (HUVECs) by inactivating tumor necrosis factor-α converting enzyme (TACE).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [164] Kuboyama, 2006, Withanoside IV and its active metabolite, sominone, attenuate Abeta(25–35)-induced neurodegeneration, Eur. J. Neurosci. source

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  • Premisecitation

    Rectal gel application of Withania somnifera root extracts (500 microg/ml and 1000 mg/kg b.w.) exhibits mucorestorative and anti-inflammatory activities by reducing neutrophil infiltration, necrosis, and edema in TNBS-induced inflammatory bowel disease.

    “Rectal gel application of WS root extracts (500 µg/ml and 1000 mg/kg b.w.) were documented to exhibit mucorestorative and anti-inflammatory activities by reducing neutrophil infiltration, necrosis, and edema in trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease [265].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [265] Perumal, 1992, Vitamin E attenuates the toxic effects of 6-hydroxydopamine on free radical scavenging systems in rat brain, Brain Res. Bull. source

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  • Premisecitation

    Cytoprotection against lead toxicity (25-400 microM) in C6 cells is found by pretreatment with 0.1% Withania somnifera extract.

    “Cytoprotection against lead toxicity (25-400 µM) in C6 cells was found by pretreatment with 0.1% WS extract [174].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [174] Kumar, 2017, Ethnomedicinal plants uses to cure different human diseases by rural and tribal peoples of Hathras district of Uttar Pradesh, J. Pharm. Phytochem

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  • Premisecitation

    In cellular models of cystic fibrosis, withaferin-A (3 microM/ml in vitro) inhibits IL-8 and NFkappaB in HEK293 cells.

    “In cellular models of cystic fibrosis, withaferin-A (3 µM/ml in vitro) led to inhibition of IL-8 and NFκB in cellular models (HEK293) of cystic fibrosis [197].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [197] Malhotra, 1965, Studies on Withania-ashwagandha, Kaul. V. The effect of total alkaloids (ashwagandholine) on the central nervous system, Indian J. Physiol. Pharmacol.

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    Premisecitation

    Withania somnifera occurs naturally in drier regions extending from the Mediterranean through tropical Africa through South Africa and from the Canary and Cape Verde Islands to the Middle East and Arabia, Afghanistan, Baluchistan, Pakistan, Sri Lanka, China, Nepal and India.

    “It occurs naturally in drier regions extending from the Mediterranean through tropical Africa through South Africa and from the Canary and Cape Verde Islands to the Middle East and Arabia, Afghanistan, Baluchistan, Pakistan, Sri Lanka, China, Nepal and India.”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [191] Mahalingam, 2014, Levy. Genetics of huntington disease, Am. J. Neuroradiol. source

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    • cites [215] Mishra, 2013, Ethnomedicinal plants used to cure the gynaecological disorders by ethnic populace of Sitapur district, Uttar Pradesh, India, Med. Plants-Int. J. Phytomedicines Relat. Ind.

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    • cites [377] Vecsey, 2009, Sleep deprivation impairs cAMP signaling in the hippocampus, Nature source

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    Premisecitation

    Roots of Withania somnifera contain 0.13-0.31% alkaloids, volatile oils, starch, amino acids, glycosides, reducing sugars, and steroids.

    “Roots are reported to contain 0.13-0.31%alkaloids, volatile oils, starch, amino acids, glycosides, reducing sugars, and steroids [199].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [199] Mallick, 2014, Study of ethnomedicinal values of some shrub in Rourkela steel city and its surroundings, Sundergarh, Odisha, Int J. Appl. Biol. Pharm. Tech.

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    Premisecitation

    Withania somnifera has been used as astringent, anti-carbuncle, anti-stress, tonic, narcotic, diuretic and against worms, piles, goitre, leucoderma, nervous breakdown, insomnia and constipation.

    “Ashwagandha has been tremendously used as astringent, anti-carbuncle, anti-stress, tonic, narcotic, diuretic and against worms, piles, goitre, leucoderma, nervous breakdown, insomnia and constipation [6,192].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [6] Agarwal, 1999, Studies on immunomodulatory activity of Withania somnifera (Ashwagandha) extracts in experimental immune inflammation, J. Ethnopharmacol. source

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    • cites [192] Mahishi, 2005, Medicinal plant wealth of local communities in some villages in Shimoga District of Karnataka, India, J. Ethnopharmacol. source

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    Premisecitation

    In India, Withania somnifera is widely distributed in the drier parts, especially in Punjab, Gujarat, Uttar Pradesh, Maharashtra, West Bengal and Rajasthan.

    “In India, the plant is widely distributed in the drier parts, especially in Punjab, Gujarat, Uttar Pradesh, Maharashtra, West Bengal and Rajasthan [169].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [169] Kumar, 2010, In vitro protective effects of Withania somnifera (L.) Dunal root extract against hydrogen peroxide and β-amyloid(1-42)-induced cytotoxicity in differentiated PC12 cells, Phytother. Res. source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Withania somnifera is an evergreen, xerophytic, woody, short, tender, perineal shrub that grows about 2 m tall and 1 m wide.

    “WS is an evergreen, xerophytic, woody, short, tender, perineal shrub that grows about 2 m tall and 1 m wide.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [75] Dar, 2019, An anti-cancerous protein fraction from Withania somnifera induces ROS-dependent mitochondria-mediated apoptosis in human MDA-MB-231 breast cancer cells, Int J. Biol. Macromol. source

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    Premisecitation

    In India, Withania somnifera is grown as a medicinal crop mainly for its fleshy roots that possess bioactive compounds having several pharmacological implications.

    “In India, however, it is grown as a medicinal crop mainly for its fleshy roots that possess a plethora of bioactive compounds having several pharmacological implications [191,215,377].”
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    • cites [191] Mahalingam, 2014, Levy. Genetics of huntington disease, Am. J. Neuroradiol. source

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    • cites [215] Mishra, 2013, Ethnomedicinal plants used to cure the gynaecological disorders by ethnic populace of Sitapur district, Uttar Pradesh, India, Med. Plants-Int. J. Phytomedicines Relat. Ind.

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    • cites [377] Vecsey, 2009, Sleep deprivation impairs cAMP signaling in the hippocampus, Nature source

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    Premisecitation

    Ashwagandha extracts in Swiss albino mice suppress cyclophosphamide-induced potentiation of DTH reaction, increase WBC and platelet counts, and reduce ovalbumin-induced edema.

    “Ashwagandha extracts in Swiss albino mice caused suppression of cyclophosphamide-induced potentiation of Delayed type hypersensitivity (DTH) reaction, a significant increase in white blood cell counts, platelet counts, and Immunoglobulin E-mediated anaphylaxis as a reduction of ovalbumin-induced edema [6].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [6] Agarwal, 1999, Studies on immunomodulatory activity of Withania somnifera (Ashwagandha) extracts in experimental immune inflammation, J. Ethnopharmacol. source

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    Premisecitation

    Oral administration of Withania somnifera root extract powder (500 and 1000 mg/kg body weight) is effective against systemic lupus erythematosus-like symptoms (nephritis, proteinuria, autoantibody production), reducing IL-6, TNF-alpha, ROS and NO in female Balb/c mouse models.

    “Oral administration of WS root extract powder (500 and 1000 mg/kg body weight) was found to be effective against systemic lupus erythematosus like symptoms (nephritis, proteinuria, autoantibody production), reducing pro-inflammatory cytokines (IL-6), Tumor necrosis factor (TNF)-α, reactive oxygen species (ROS) and nitric oxide (NO) in female Balb/c mouse models [212,213].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [212] Mirjalili, 2009, Steroidal lactones from Withania somnifera, an ancient plant for novel medicine, Molecules source

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    • cites [213] Misra, 2005, Unusually sulfated and oxygenated steroids from Withania somnifera, Phytochemistry source

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    Premisecitation

    Withanolides have antitumor, anti-inflammatory, and immunosuppressant characters and are potent antioxidants implicated in the neuroprotection ability of the plant extract.

    “Besides having antitumor, anti-inflammatory, and immunosuppressant characters, they are potent antioxidants implicated in the neuroprotection ability of the plant extract [63,106].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [63] Canevari, 2004, Toxicity of Amyloid β Peptide: Tales of calcium, mitochondria, and oxidative Stress, Neurochem Res source

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    • cites [106] Gannon, 2019, Effects of a standardized extract of Withania somnifera (Ashwagandha) on depression and anxiety symptoms in persons with schizophrenia participating in a randomized, placebo-controlled clinical trial, Ann. Clin. Psychiatry.: Off. J. Am. Acad. Clin. Psychiatr. source

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    Premisecitation

    Polyherbal formulations containing Withania somnifera (50, 75, and 100 mg/ml, in vitro) provide cardio-protection against doxorubicin-induced cardiotoxicity in animals by activating Nrf-2, stimulating phase-II detoxification enzymes, and evading apoptosis in an Nrf-2-dependent manner in HL-1 cardiomyocytes.

    “Polyherbal formulations which contained WS (50, 75, and 100 mg/ml, in vitro) also provides cardio-protection (doxorubicin-induced) in animals ( [220,367]) by activating a transcription factor known as nuclear factor-erythroid-2(Nrf)-2, which stimulates phase-II detoxification enzymes, thereby evading apoptosis in an Nrf-2-dependent manner in HL-1 cardiomyocytes [295].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [220] Mohanty, 2008, Withania somnifera provides cardioprotection and attenuates ischemia-reperfusion induced apoptosis, Clin. Nutr. source

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    • cites [367] Tripathi, 2021, Identification of bioactive molecule from Withania somnifera (Ashwagandha) as SARS-CoV-2 main protease inhibitor, J. Biomol. Struct. Dyn. source

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    • cites [295] Sachan, 2015, Ethno-Medicinal Flora vis-à-vis agro-climatic conditions of Uttar Pradesh, J. Med Plants Stud.

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    Premisecitation

    Patients administered root powder of Withania somnifera (3 g/day for 30 days) have stabilized blood glucose comparable to oral hypoglycemic drug Daonil with no adverse effects.

    “Patients administered with root powder of WS (3 g/day to each human subject for 30 days) were observed to have a stabilized blood glucose concentration that could be compared to the effect of an oral hypoglycemic drug Daonil [24] with no adverse effects.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [24] Andallu, 2000, Hypoglycemic, diuretic and hypocholesterolemic effect of winter cherry (Withania somnifera, Dunal) root, Indian J. Exp. Biol.

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    Premisecitation

    Administration of Withania somnifera leaves and root extracts increases survival rate and reduces bacterial load in various organs of Balb/c mice suffering from salmonellosis.

    “Additionally, an increase in the rate of survival and reduction in bacterial load in various organs of Balb/c mice suffering from salmonellosis was reported after administration of WS leaves and root extracts [248].”
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    • cites [248] Pandey, 2018, Multifunctional neuroprotective effect of Withanone, a compound from Withania somnifera roots in alleviating cognitive dysfunction, Cytokine source

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    Premisecitation

    Withaferin-A from Withania somnifera blocks inflammatory responses caused by cytokine-induced damage to islets of Langerhans in vitro after transplantation and exhibits anti-glycating activity.

    “In addition, withaferin-A from WS could block the inflammatory responses caused due to cytokine-induced damage to the islets of Langerhans in vitro after transplantation and it exhibited potential anti-glycating activity [33,357].”
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    • cites [33] Bahadur, 2020, Traditional usage of medicinal plants among the local communities of Peshawar valley, Pakistan, Acta Ecol. Sin. source

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    • cites [357] Tariq, 2013, Ethnobotanical Survey of Medicinal Plants in Yelagiri Hills of Tamil Nadu, Res. J. Pharm. Technol.

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    Premisecitation

    Methanolic root extract of Withania somnifera promotes attenuation of proliferative, metastatic, and angiogenic signals mediated by IL-8 and COX-2 expression and cell cycle arrest in G2/M phase in prostate cancer PC3 cells with an IC50 dose of 10 microg/ml.

    “The methanolic root extract also promotes attenuation of proliferative, metastatic, and angiogenic signals mediated by interleukin-8 and cyclooxygenase-2 expression and cell cycle arrest in the G2/M phase in prostate cancer PC3 cells with an IC50 dose of 10 µg/ml [36].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Balkrishna, A., Pokhrel, S., Singh, J. and Varshney, A. (2020). 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 (Research Square Preprint). DOI:10.21203/rs-17806/v1. source

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    Premisecitation

    Withanolides inhibit acetylcholinesterase and promote the formation of dendrites in human neuroblastoma cells.

    “Besides, withanolides possess the ability to inhibit acetylcholinesterase and promote the formation of dendrites in human neuroblastoma cells [369,404].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [369] Udayakumar, 2009, Hypoglycaemic and hypolipidaemic effects of Withania somnifera root and leaf extracts on alloxan-induced diabetic rats, Int J. Mol. Sci. source

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    • cites [404]

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    Premisecitation

    Aqueous root extracts of Withania somnifera (0.05-0.4 mg/ml) modulate PBMC and leukemic THP-1 cell viability, increase oxidant scavenging and caspase (8, 9, 3/7) activities, and decrease TNF-alpha, IL-10 and GSH levels.

    “Aqueous root extracts of WS (0.05-0.4 mg/ml) can modulate peripheral blood mononuclear cell (PBMC) and leukemic THP-1 cell viability, increase oxidant scavenging and caspase (8, 9, 3/7) activities, at the same time decrease tumor necrosis factor-alpha (TNF-α), interleukin (IL)-10 and Glutathione (GSH) levels [238].”
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    • cites [238] Nisar, 2014, Ethno-medicinal uses of plants from district Bahawalpur, Pakistan, Curr. Res. J. Biol. Sci. source

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    Premisecitation

    Withaferin-A (2 microM in vitro) prevents IkappaB kinase activation and phosphorylation, blocking NFkappaB translocation, binding of NFkappaB and DNA, and transcription in murine fibrosarcoma L929sA cells.

    “Withaferin-A from the extracts (2 µM in vitro) prevented Iκb kinase activation and phosphorylation, which further blocked the translocation of NFκB, binding of NFκB and DNA, and transcription in murine fibrosarcoma L929sA cells [148].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [148] Kannan, 2016, Ethnomedicinal plants used for Wound Healing purposes by Malayali Tribes of Kalrayan Hills, Salem district, Tamil Nadu, India, Glob. J. Res. Med. Plants Indig. Med.

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    Premisecitation

    Treatment with Withania somnifera (50 mg/kg b.w. for 30 days) in Wistar rats restores balance between myocardial oxidant and antioxidant, anti-apoptotic and pro-apoptotic effects, and reduces histopathologic deterioration of myocardium and TUNEL positivity.

    “Treatment with WS (50 mg/kg b.w. for 30 days) in wister rats significantly restored the balance between myocardial oxidant and antioxidant [31,119,222], anti-apoptotic and pro-apoptotic effects, and further reduced histopathologic deterioration of myocardium and triphosphate nick-end labeling (TUNEL) positivity (apoptosis) in rat models [223].”
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    • cites [31] Ashour, 2012, Evaluation of the potential cardioprotective activity of some Saudi plants against doxorubicin toxicity, Z. Nat. C.

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    • cites [119] Gupta, 2019, Withania somnifera (L.) Dunal ameliorates neurodegeneration and cognitive impairments associated with systemic inflammation, BMC Complement. Altern. Med. source

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    • cites [222] Mohanty, 2015, Herbal folk remedies of Dhenkanal district, Odisha, India, Int. J. Herb. Med.

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    • cites [223] Mohanty, 2016, Withania somnifera Leaf Extract Ameliorates Benzo[a]pyrene-Induced Behavioral and Neuromorphological Alterations by Improving Brain Antioxidant Status in Zebrafish (Danio rerio), Zebrafish source

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    Premisecitation

    Ethanolic extract of Withania somnifera is cytotoxic (99.7 microg/ml), an inducer of apoptosis, and an inhibitor of cell migration and angiogenesis.

    “Ethanolic extract of WS is cytotoxic (99.7 µg/ml), an inducer of apoptosis, and an inhibitor of cell migration and angiogenesis [271].”
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    • cites [271] Prakash, 2014, Withania somnifera alleviates parkinsonian phenotypes by inhibiting apoptotic pathways in dopaminergic neurons, Neurochem. Res. source

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    Premisecitation

    Withaferin-A protects the integrity of the vascular barrier of HUVECs in mice induced by HMGB1 by inhibiting CAMs, hyperpermeability, migration, adhesion of leukocytes, production of TNF-alpha, IL-6 and activation of NFkappaB.

    “Withaferin-A protected the integrity of the vascular barrier of HUVECs in mice, which was induced by High Mobility Group Box 1 (HMGB1) by inhibiting the expression of Calmodulin (CAMs), inflicting hyperpermeability, migration, and adhesion of leukocytes, production of TNF-α, IL-6 and activation of nuclear factor of j-light polypeptide gene enhancer in B-cells (NFκB) [186].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [186] Lopresti, 2019, A randomized, double-blind, placebo-controlled, crossover study examining the hormonal and vitality effects of ashwagandha (Withania somnifera) in aging, overweight males, Am. J. Men. ’S. Health

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    Premisecitation

    Standardized Withania somnifera extracts (1.5% withanolides) at 300 mg/kg prevent doxorubicin-induced cardiotoxicity and restore biochemical changes including reduction in elevated malondialdehyde, catalase, superoxide dismutase activity, calcium content, and Bcl-2 protein levels.

    “Furthermore, standardized WS extracts (1.5% withanolides) at a dose of 300 mg/kg prevented cardiotoxicity induced by doxorubicin and restored several biochemical changes like reduction in elevated malondialdehyde level, catalase, superoxide dismutase activity, calcium content, Bcl-2 protein levels [127].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [127] Heyninck, 2014, Withaferin A inhibits NFkappaB activation by targeting cysteine 179 in IKKbeta, Biochem Pharm. source

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    Premisecitation

    Root extracts of WS cut down lipid peroxidation and nitrite levels and escalated the activity of antioxidant enzymes.

    “[171] validated the same as they presented that root extracts of WS efficiently cut down the lipid peroxidation and nitrite levels and escalated the activity of the antioxidant enzymes.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [171] Kumar, 2014, Glioprotective effects of Ashwagandha leaf extract against lead induced toxicity, BioMed. Res. Int.

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    Interpretationreasoning

    WS extracts acted as a tonic, energy rejuvenator, and stimulant due to the presence of amino acids, proteins, starch, reducing sugar, and steroidal lactones.

    “WS extracts acted as a tonic, energy rejuvenator, and stimulant due to the presence of an array of amino acids, proteins, starch, reducing sugar, and steroidal lactones.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Withanosides and withanolides minimize accumulation of β-amyloid peptides and oligomers in the brain and transport them to the periphery.

    “The withanosides and withanolides present in the plant extract could minimize the accumulation of β-amyloid peptides and oligomers in the brain and transport them to the periphery [181,311].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [181] Kushwaha, 2021, Phytochemicals present in Indian ginseng possess potential to inhibit SARS-CoV-2 virulence: A molecular docking and MD simulation study, Microb. Pathog. source

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    • cites [311] Shah, 2017, Ethnomedicinal uses of plants for the treatment of malaria in Soon Valley, Khushab, Pakistan, J. Ethnopharmacol. source

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    Premisecitation

    WS root extract brings down nitric oxide production by inhibiting activation of stress-induced NADPH-diaphorase in the brain, achieved through activating choline acetyltransferase and suppressing corticosterone release.

    “The root extract has been reported to bring down nitric oxide production by inhibiting the activation of stress-induced Nicotinamide adenine dinucleotide phosphate reduced (NADPH)-diaphorase (NADPH-d) in the brain.”
    • Also stated in: § 1.11. Neuroprotective activity · plain
      “This is achieved through activating choline acetyltransferase and suppressing the release of corticosterone [47].”
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    • cites [47] Bhatt, 2008, Indigenous plants in traditional healthcare system in Kedarnath valley of western Himalaya, Indian J. Tradit. Knowl.

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    Premisecitation

    Withania somnifera protects packed cell volume drop effect and reduces parasite load in malarial mice with MIC 600 mg/kg; leaves and root bark extracts show 50.43% and 29.13% parasite inhibition.

    “WS protected the packed cell volume drop effect and reduced parasite load d in malarial mice with a MIC of 600 mg/kg, leaves and root bark extracts showed 50.43% and 29.13% parasite inhibition [90].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [90] Donkor, 2018, Stroke in the 21st century: a snapshot of the burden, epidemiology, and quality of life, Stroke Res Treat. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    WS extract inhibits lipid peroxidation and revitalizes nerve cells.

    “The extract exhibited the tremendous potential to inhibit lipid peroxidation and revitalize the nerve cells.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Withania somnifera extracts significantly reduce neuronal cell markers (MAP-2, NF-H, GAP-43, PSD-95), glial marker GFAP, and oxidative stress markers of DNA.

    “Several neuronal cell markers [Microtubule-associated protein 2 (MAP-2)], Neurofilament (NF)-H, Growth Associated Protein 43 (GAP-43) and postsynaptic density protein 95 (PSD-95)], markers of glial cells [glial fibrillary acidic protein (GFAP)] and oxidative stress markers of DNA is found to be significantly reduced by WS extracts [162].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [162] Kuboyama, 2002, Axon- or dendrite-predominant outgrowth induced by constituents from Ashwagandha, NeuroReport source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    1000 mg of standardized WS extract showed potent activity in the treatment of anxiety and depression caused by schizophrenia in a human trial, with mild and transient adverse effects.

    “With mild and transient adverse effects, 1000 mg of standardized WS extract showed potent activity in the treatment of anxiety and depression caused by schizophrenia in a human trial [109].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [109] Ghatapanadi, 2011, Documentation of folk knowledge on medicinal plants of Gulbarga district, Karnataka, Indian J. Nat. Prod. Resour.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    WS up-regulates LRP, β-amyloid peptide-degrading protease neprilysin, and dopaminergic D2 receptor.

    “Certain neuronal receptors and their activities were up-regulated when treated with WS such as low-density lipoprotein receptor-related protein (LRP), β-amyloid peptide-degrading protease neprilysin [311], and dopaminergic D2 receptor [286].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [311] Shah, 2017, Ethnomedicinal uses of plants for the treatment of malaria in Soon Valley, Khushab, Pakistan, J. Ethnopharmacol. source

      Not checked in the free run.

    • cites [286] Rampilla, 2015, Ethno-Medicinal Plants in Sacred Groves in East Godavari District, Andhra Pradesh, India, Eur. J. Med. Plants source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationnone given

    The antioxidant property of WS is mainly due to the presence of phenolics.

    “The antioxidant property is mainly due to the presence of phenolics.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    WS heals severely damaged neurons by regenerating neurites and reconstructing synapses.

    “It could heal severely damaged neurons by regenerating neurites and reconstructing synapses [166].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [166] Kulkarni, 2008, Withania somnifera: an Indian ginseng, Prog. neuro-Psychopharmacol. Biol. Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Withanoside-IV induced both axons and dendrites and restored synapses in rat cortical neurons damaged by amyloid-b (dose 10 μM/kg/day).

    “However, withanoside-IV induced both axons and dendrites and restored synapses in rat cortical neurons that were damaged by amyloid-b (Ab) (dose: 10 µM/kg/day) [165,167].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [165] Kuboyama, 2014, Effects of Ashwagandha (roots of Withania somnifera) on neurodegenerative diseases, Biol. Pharm. Bull. source

      Not checked in the free run.

    • cites [167] Kumar, 1995, Free radical-generated neurotoxicity of 6-hydroxydopamine, J. Neurochem. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Pre-treatment with WS inhibited glutamate-induced cell death by upregulating HSP70 and restoring neuronal plasticity in neural CAMs and its polysialylated form.

    “Pre-treatment with WS inhibited cell death by glutamate induction which further induced reversal of glutamate evoked a stress response by upregulating HSP70 and restoring neuronal plasticity in neural CAMs, and its polysialylated form [152].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [152] Khan, 2005, Herbal folklores for male sexual disorders and debilities in western Uttar Pradesh, Indian J. Tradit. Knowl.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    While 15 days of oral administration of hydroalcoholic extract of WS did not improve stroke symptoms, 30 days of oral treatment restored motor functioning in rats subjected to cerebral ischemia.

    “While 15 days of oral administration of the hydroalcoholic extract of WS did not improve the symptoms of stroke, 30 days of oral treatment restored motor functioning in treated rats.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [69] Chengappa, 2018, Adjunctive Use of a Standardized Extract of Withania somnifera (Ashwagandha) to Treat Symptom Exacerbation in Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study, J. Clin. Psychiatry

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Ethanolic root extract of WS restored impaired motor movements, brought down MDA and NO levels, enhanced catalase activity, and revived tyrosine hydroxylase positive neurons, reducing oxidative stress and protecting dopaminergic neurodegradation elicited by PQ and MB toxicity in Swiss albino mice.

    “The ethanolic root extract of WS was reported to restore impaired motor movements, bring down MDA and NO levels, enhance catalase activity and revive tyrosine hydroxylase (TH) positive neurons, all of which in turn reduce oxidative stress and protect dopaminergic neurodegradation elicited by PQ and MB toxicity in Swiss albino mice [273].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [273] Prakasha, 2010, Folk medicine of NR Pura taluk in Chikmagalur district of Karnataka, Indian J. Tradit. Knowl.

      Not checked in the free run.

  • May combine two claims.

    Premisereasoning

    Chronic treatment with root extract of WS suspended in 0.5% carboxymethyl cellulose increased weight and improved motor movement in 3-NP treated rats owing to its anabolic, adaptogenic and antioxidant properties restoring energy balance.

    “Chronic treatment with root extract of WS suspended in 0.5% carboxymethyl cellulose (0.5 ml/100 g b.w.) was found to increase weight and improve motor movement in 3-NP treated rats owing to its anabolic, adaptogenic and anti-oxidant properties that are effective in restoring the energy balance.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Root extracts of WS play a pivotal role against anxiety, depression, senile dementia, cognitive disorder, and other neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease.

    “The root extracts of the plant have been found to play a pivotal role against anxiety, depression, senile dementia, cognitive disorder, and many other neurodegenerative disorders (such as Alzheimer's disease and Parkinson's disease).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Mamsyadi Kwatha, an Ayurvedic compound formulation containing WS, exhibited profound antidepressant activity in Swiss albino mice via reversing behavioral despair and exhibiting anti-reserpine activity.

    “Mamsyadi Kwatha, an Ayurvedic compound formulation (ingredients: Nardostachys jatamansi, W. somnifera, and Hyoscyamus niger in 8:4:1 ratio) exhibited profound antidepressant activity in Swiss albino mice via reversing behavioral despair remarkably and via exhibiting anti-reserpine activity [332].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [332] Sindhu, 2005, Behavioral differences in a rotenone-induced hemiparkinsonism rat model following intranigral or median forebrain bundle infusion, Brain Res source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Intake of Shoden beads for 8 weeks showed increased testosterone and Dehydroepiandrosterone sulfate (DHEA-S) (18%) resulting in sexual and psychological well-being with more vigour and less fatigue in a randomized, double-blind, placebo-controlled, crossover study among overweight males.

    “Intake of Shoden beads for 8 weeks showed increased testosterone and Dehydroepiandrosterone sulfate (DHEA-S) (18%) resulting IN sexual and psychological well-being with more vigour and less fatigue in a randomized, double-blind, placebo-controlled, crossover study among overweight males [189].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [189] Machiah, 2006, Purification of a post-synaptic neurotoxic phospholipase A2 from Naja naja venom and its inhibition by a glycoprotein from Withania somnifera, Biochimie source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    300 mg twice a day of WS root standardized to 1.5% withanolides along with dietary counseling, deep breathing, relaxation techniques, and standard multivitamin significantly improved mental health, concentration, vitality, and social function leading to a better quality of life without serious adverse effects.

    “Three hundred mg twice a day standardized to 1.5% withanolides from WS root along with dietary counseling, deep breathing, relaxation techniques, and standard multivitamin significantly improved mental health, concentration, vitality, and social function leading to a better quality of life without any serious adverse effects [74].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [74] Dar, 2015, Pharmacologic overview of Withania somnifera, the Indian Ginseng, Cell. Mol. life Sci. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    With a dose of 2 g every 8 h, root extract of WS caused lower fatigue scores and improvement in quality of life in breast cancer patients receiving chemotherapy.

    “With a dose of 2 g every 8 h, the root extract of WS caused lower fatigue scores (Schwartz Cancer Fatigue Scale) and improvement in quality of life in breast cancer patients receiving chemotherapy [59].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [59] Blum, 2001, Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson’s disease, ProgNeurobiol

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Withanolide-free root extract of WS up to 10 mg/kg/day in mice protected against stress-induced changes in blood glucose and insulin levels and acted as an antidepressant at higher doses of 33.3 and 100 mg/kg/day.

    “Withanolide free root extract of WS, up to a dose of 10 mg/kg/day in mice can act as triethylene glycol (TEG) in response to stress-triggered changes.It also protected against stress-induced changes in blood glucose and insulin levels and acted as an antidepressant in higher doses of 33.3 and 100 mg/kg/day [86].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [86] Dhawale, 2015, Ethnomedicinal Survey Of Yavatmal District (MS), Asian J. Pharm. Sci. Technol.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    12 hr sleep-deprived rats exhibited neuromotor dysfunction and memory impairments, which could be reverted with pretreatment before sleep deprivation with WS extract for 15 days.

    “In the study, 12 hr sleep-deprived rats were found to exhibit neuromotor dysfunction and memory impairments, which could be reverted with pretreatment before sleep deprivation with WS extract for 15 days.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [204] Marandi, 2015, Antivenom herbal formulations used against snakebites by the Oroan tribals of Latehar, Jharkhand, World J. Pharm. Res

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    In a study involving 60 adults, WS plant extract reduced stress significantly without side effects compared to placebo.

    “In another study, involving 60 adults, the plant extract was found to reduce stress significantly without any side effects compared to the placebo group.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [189] Machiah, 2006, Purification of a post-synaptic neurotoxic phospholipase A2 from Naja naja venom and its inhibition by a glycoprotein from Withania somnifera, Biochimie source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    WSE improved auditory-verbal working memory and social cognition in patients of bipolar disorder with cognitive dysfunction.

    “WSE also improved auditory-verbal working memory and social cognition in patients of bipolar disorder with cognitive dysfunction [70].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [70] Choi, 2015, Withaferin-A inhibits colon cancer cell growth by blocking STAT3 transcriptional activity, J. Cancer Prev. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    20 and 50 mg/kg of aqueous concentrate of WS roots in inbred Charles Foster strain male rats showed a GABA-mimetic effect and can act as a potential antidepressant.

    “In addition, 20 and 50 mg/kg of aqueous concentrate of WS roots in inbred Charles Foster strain male rats could show its GABA-mimetic effect hence can act as a potential antidepressant [52].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [52] Bhattacharya, 2003, Adaptogenic activity of Withania somnifera: an experimental study using a rat model of chronic stress, Pharm. Biochem Behav. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Standard water extract of WS improved cognitive and psychomotor performance in a double-blind, multi-dose, placebo-controlled, crossover study among 20 healthy males, with significant improvements in reaction time, choice, discrimination, card sorting, digit vigilance, and digit symbol substitution.

    “Standard water extract of WS improved cognitive and psychomotor performance in a double-blind, multi-dose, placebo-controlled, crossover study among 20 healthy males.Significant improvements in reaction time, choice, discrimination, card sorting, digit vigilance, and digit symbol substitution were noted [269].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [269] Prabhulkar, 2012, Microbiosensor for Alzheimer’s diseasediagnostics: detection of amyloid beta biomarkers, J. Neurochem. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Acute toxicity (LD50) of total alkaloids isolated from WS roots was 465 mg/kg in rats and 432 mg/kg in mice.

    “In a central nervous system study, the acute toxicity (LD 50 ) of total alkaloids isolated from the roots was 465 mg/kg and 432 mg/kg in rats and mice, respectively.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [200] Manchanda, 2017, Withania somnifera leaf alleviates cognitive dysfunction by enhancing hippocampal plasticity in high fat diet induced obesity model, BMC Complement Alter. Med source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    EuMil reduces glucose intolerance and normalizes male sexual behavior.

    “EuMil is also seen to reduce glucose intolerance and normalize male sexual behavior [407].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [407]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Cardipro, containing WS along with Terminalia arjuna, Phyllanthus emblica, and Ocimum tenuiflorum, improved the condition of coronary artery disease patients, with significant reduction of systolic and diastolic blood pressure, decreased serum cholesterol and triglycerides, and increased HDL cholesterol without marked side effects.

    “WS along with Terminalia arjuna, Phyllanthus emblica (= Emblica officinalis), and Ocimum tenuiflorum (= O. sanctum) in a capsule form (Cardipro) twice daily improved the condition of coronary artery disease (CAD) patients.Following the treatment, a significant reduction of systolic and diastolic blood pressure was observed along with decreased serum cholesterol, triglycerides, and increased high-”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [99] Fahn, 2000, The spectrum of levodopa-induced dyskinesias, Ann. Neurol.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A standardized WS extract (Shoden beads) (240 mg) once daily for 60 days in a double-blind, placebo-controlled, randomized study significantly decreased morning cortisol and depression according to Hamilton Anxiety Rating Scale (HAM-A).

    “A standardized WS extract (Shoden beads) (240 mg) once daily for 60 days in a double-blind, placebo-controlled, randomized study significantly deceased morning cortisol and depression according to Hamilton Anxiety Rating Scale (HAM-A) [190].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [190] Mahajan, 2007, Traditional herbal remedies among the tribes of Bijagarh of West Nimar district, Madhya Pradesh, Indian J. Tradit. Knowl.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    High-concentration full-spectrum extract of WS root (300 mg capsule for 60 days) significantly reduced serum cortisol and provided resistance towards stress in a double-blind, randomized, placebo-controlled trial.

    “High-concentration full-spectrum extract of WS root (300 mg capsule for 60 days) significantly reduced serum cortisol and provided resistance towards stress in a double-blind, randomized, placebo-controlled trial [68].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [68] Chengappa, 2013, Randomized placebo-controlled adjunctive study of an extract of Withania somnifera for cognitive dysfunction in bipolar disorder, J. Clin. Psychiatry source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A root extract of WS reversed TDP-43 proteinopathy in mouse ALS/FTLD and significantly reversed cytoplasmic mislocalization of hTDP-43 when administered orally in hTDP-43 A315T mice.

    “A root extract of WS reversed transactive response DNA binding protein 43 (TARDBP or TDP-43) proteinopathy in mouse ALS/FTLD.The extract significantly reversed the cytoplasmic mislocalization of hTDP-43 when administered in hTDP-43 A315T mice orally and was suggested as a promising therapeutic agent against TDP-43 proteinopathy [96].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [96] Dwivedi, 2000, Modification of coronary risk factors by medicinal plants, J. Med. Aromat. Plant Sci.

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    WS showed an immunomodulatory effect by reducing glial activation, inducing autophagy, preventing NF-κB phosphorylation, and changing expression of multiple cytokines/chemokines.

    “WS showed an immunomodulatory effect by reducing glial activation remarkably, via inducing autophagy, and via preventing nuclear factor kappaB (NF-κB) phosphorylation besides changing the expression of multiple cytokines/chemokines [98].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [98] Esakkimuthu, 2019, Quantitative analysis of medicinal plants used to treat musculoskeletal ailments by non-institutionally trained siddha practitioners of Virudhunagar district, Tamil Nadu, India, J. Ayurveda Integr. Med. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Pretreatment with WS extract improved alertness, recognition memory, and explorative nature among rats.

    “Pre-treatment was also found to improve alertness, recognition memory, and explorative nature among rats.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [204] Marandi, 2015, Antivenom herbal formulations used against snakebites by the Oroan tribals of Latehar, Jharkhand, World J. Pharm. Res

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Treatment with WS improved semen quality and sperm motility of infertile males, reduced oxidative stress, inhibited lipid peroxidation, and increased antioxidants.

    “Treatment with WS improved semen quality and sperm motility of infertile males.It reduced oxidative stress, inhibited lipid peroxidation with an increase in antioxidants [10].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [10] Ahmad, 2010, Withania somnifera improves semen quality by regulating reproductive hormone levels and oxidative stress in seminal plasma of infertile males, Fertil. Steril. source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    Withaferin A at 10 mg/kg in a 4T1 spontaneous/orthotopic mouse mammary carcinoma model inhibits Ras-Mnk and PI3-AKT-mTOR.

    “Inhibition of Ras-Mnk and”
    • Also stated in: § 6. Conclusions · plain
      “PI3-AKT-mTOR, inhibition”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [293] Ritumala, 2019, Traditional Uses of Plants for Human Use-A Case Study from Kirtinagar Region of Garhwal Himalaya, J. Agric. Technol.

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Withanone from WS was predicted to inhibit COVID-19 replication by interacting with N343 to reduce spike glycosylation.

    “Withanone from WS was predicted to inhibit COVID-19 replication by interacting with N343 to reduce spike glycosylation [264].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [264] Perese, 1989, A 6-hydroxydopamine-induced selective parkinsonianrat model, Brain Res. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Selegiline and other drugs for neurodegenerative disease only delay disease progression and provide symptomatic relief.

    “and selegiline, but they are only able to delay the progression of the disease and provide symptomatic relief [390].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [390] Yadav, 2003, Ethanomedicinal uses of some important plants of Jhajjar district, Haryana, India, Environ. Conserv. J. source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    Withaferin A downregulates cancer stem cells.

    “downregulation of cancer”
    • Also stated in: § 6. Conclusions · plain
      “stem cells”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [124] Hamza, 2008, The protective effect of a purified extract of Withania somnifera against doxorubicin-induced cardiac toxicity in rats, Cell Biol. Toxicol. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Four compounds from WS inhibit COVID-19 envelope (E) protein by binding with the pore region and reduce viral replication.

    “Four compounds from WS have been found to inhibit COVID-19 envelope (E) protein by binding with the pore region and reduce viral replication [3].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [3] Alharbi, 2021, Structure Insights of SARS-CoV-2 open state envelope protein and inhibiting through active phytochemical of ayurvedic medicinal plants from Withania somnifera, Saudi J. Biol. Sci. source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    These findings suggest potent antiviral especially anti-SARS-CoV2 activity, but the in silico findings need validation in in vitro and in vivo systems.

    “These findings suggest potent antiviral especially anti-SARS-CoV2 activity but these in silico findings are needed to be validated in”
    Quote in the paperSubstantial claim

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    Withaferin A induces ROS and autophagy.

    “Induction of ROS and”
    • Also stated in: § 6. Conclusions · plain
      “Autophagy”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [303] Sankar, 2007, The neuroprotective effect of Withania somnifera root extract in MPTP-intoxicated mice: an analysis of behavioral and biochemical variables, Cell MolBiolLett

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A preprint predicts withanone from WS could bind with the receptor-binding domain complex of COVID-19 spike protein and human angiotensin-converting enzyme 2 (ACE-2) and concomitantly reduce viral entry.

    “A preprint from Balkrishna et al. [37] predicts withanone from WS could bind with receptor-binding domain (RBD) complex of COVID-19 spike protein and human angiotensin-converting enzyme 2 (ACE-2) and concomitantly reduce viral entry.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [37] Banerjee, 2021, Bacosides from Bacopa monnieri extract: an overview of the effects on neurological disorders, Phytother. Res.: PTR source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    Withaferin A at 4 mg/kg in a 4T1 spontaneous mouse mammary carcinoma model causes phosphorylation and disassembly of Vimentin.

    “Phosphorylation and”
    • Also stated in: § 6. Conclusions · plain
      “disassembly of Vimentin”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [365] Tomita, 2021, Withanolide Derivative 2, 3-Dihydro-3β-methoxy Withaferin-A Modulates the Circadian Clock via Interaction with RAR-Related Orphan Receptor α (RORa), J. Nat. Prod. source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    Withaferin A at 100 μg in MMTV-neu mice inhibits self-renewal of cancer stem cells.

    “self-renewal of cancer stem”
    • Also stated in: § 6. Conclusions · plain
      “cells”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [161] Ku, 2014, Withaferin A is an inhibitor of endothelial protein C receptor shedding in vitro and in vivo, Food Chem. Toxicol. source

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    Withaferin A at 3.6 mg/kg in a Panc-1 xenograft in nude mice inhibits HSP90 and causes degradation of Akt and Cdk4.

    “HSP90 inhibition and”
    • Also stated in: § 6. Conclusions · plain
      “degradation of Akt and”
    • Also stated in: § 6. Conclusions · plain
      “Cdk4”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [302] Sandhu, 2010, Effects of Withania somnifera (Ashwagandha) and Terminalia arjuna (Arjuna) on physical performance and cardiorespiratory endurance in healthy young adults, Int J. Ayurveda Res source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    Withaferin A at 20 μg in a TPA skin cancer model inhibits transcription of the ACC1 gene.

    “inhibition of transcription”
    • Also stated in: § 6. Conclusions · plain
      “of ACC1 gene”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [405]

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Commonly available drugs to treat neurodegenerative diseases include galantamine, donepezil, rivastigmine, and selegiline, but they are only able to delay the progression of the disease and provide symptomatic relief.

    “The commonly available drugs to treat neurodegenerative diseases include galantamine, donepezil, rivastigmine, and selegiline, but they are only able to delay the progression of the disease and provide symptomatic relief [390].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [390] Yadav, 2003, Ethanomedicinal uses of some important plants of Jhajjar district, Haryana, India, Environ. Conserv. J. source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    LD50 of aqueous methanol extract of WS by intraperitoneal administration in mice was 1076 ± 78 mg/kg, and that of an equimolar combination of sitoindosides VII and VIII and withaferin-A was 1564 ± 92 mg/kg.

    “LD 50 of aqueous methanol extract of WS by intraperitoneal (i.p.) administration in mice was 1076 ± 78 mg/kg and that of an equimolar combination of sitoindosides VII and VIII and withaferin-A was 1564 ± 92 mg/kg [117].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [117] Gupta, 2013, Efficacy of Withania somnifera on seminal plasma metabolites of infertile males: a proton NMR study at 800 MHz, J. Ethnopharmacol. source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    Withaferin A at 4 mg/kg in an MDA-MB 231 xenograft in nude mice induces FOXO3a- and Bim-dependent apoptosis.

    “FOXO3a and Bim”
    • Also stated in: § 6. Conclusions · plain
      “dependent apoptosis”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [335] Singh, 2007, Pesticides and metalsinduced Parkinson’s disease: involvement of free radicals andoxidative stress, Cell Mol. Biol.

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    Withaferin A at 8 mg/kg downregulates HPV16 E6 and E7 and increases p53 protein levels.

    “Downregulation of HPV16”
    • Also stated in: § 6. Conclusions · plain
      “E6 and E7, increasing p53”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [232] Mushtaq, 2012, Ethnomedicinal Investigation of Phytomedicines among the local communities of Arid areas of Pakistan, Indian J. Tradit. Knowl.

      Not checked in the free run.

  • May combine two claims. The quote only partly states this claim.

    Premisecitation

    Withaferin A inhibits AKT and inhibits c-MET activation.

    “Inhibition of AKT,”
    • Also stated in: § 6. Conclusions · plain
      “inhibition of c-MET”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [303] Sankar, 2007, The neuroprotective effect of Withania somnifera root extract in MPTP-intoxicated mice: an analysis of behavioral and biochemical variables, Cell MolBiolLett

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Withania somnifera possesses immunomodulation, anti-cancer, anti-depressant, neuroprotective, and other biological properties.

    “Withania somnifera happens to be one of the prime examples of the Rasyana medicinal plant which possesses immunomodulation, anti-cancer, anti-depressant, neuroprotective, and other biological properties [73].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [73] Da Silva, V.G. (2005). Candomblé e umbanda: caminhos da devoção brasileira. Selo Negro.

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    Premisecitation

    Withaferin A at 8 mg/kg in a DRO81-1 xenograft in nude mice inhibits RET proto-oncogene phosphorylation and activation.

    “Inhibition of RET proto-”
    • Also stated in: § 6. Conclusions · plain
      “oncogene phosphorylation”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [232] Mushtaq, 2012, Ethnomedicinal Investigation of Phytomedicines among the local communities of Arid areas of Pakistan, Indian J. Tradit. Knowl.

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    Premisecitation

    Withaferin A at 4 mg/kg in an MDA-MB 231 xenograft in nude mice activates ERK/RSK and CHOP/Elk1 and upregulates DR5.

    “Activation of ERK/RSK and”
    • Also stated in: § 6. Conclusions · plain
      “CHOP/Elk1, upregulation”
    • Also stated in: § 6. Conclusions · plain
      “of DR5”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [401] Muruganandam, 2002, Effect of poly herbal formulation, EuMil, on chronic stress-induced homeostatic perturbations in rats., Indian J. Exp. Biol.

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    Withaferin A at 100 μg in MMTV-neu mice suppresses glycolysis and the tricarboxylic acid (TCA) cycle.

    “Suppression of glycolysis”
    • Also stated in: § 6. Conclusions · plain
      “and Tricarboxylic acid”
    • Also stated in: § 6. Conclusions · plain
      “(TCA) cycle. Inhibition of”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [161] Ku, 2014, Withaferin A is an inhibitor of endothelial protein C receptor shedding in vitro and in vivo, Food Chem. Toxicol. source

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    Premisecitation

    Root and leaf extract at 200 mg/kg b.wt. for 8 weeks normalizes blood glucose, urine sugar, tissue glycogen levels, and glucose-6-phosphatase.

    “Normalized the blood”
    • Also stated in: § 6. Conclusions · plain
      “glucose, urine sugar, tissue”
    • Also stated in: § 6. Conclusions · plain
      “glucose-6-phosphatase”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [376] Vaidyanathan, 2014, Survey of Ethnomedicinal Plants and Folklore Studies On Malayali Tribals Of Vellakadai Village A Part Of Shervaroy Range In Eastern Ghats, Tamil Nadu, Int. J. Recent Sci. Res.

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    Premisecitation

    Glycoproteins at 20 μg/ml inhibit hyphal growth and spore germination.

    “Inhibiting hyphal growth”
    • Also stated in: § 6. Conclusions · plain
      “and spore germination”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [115] Grover, 2012, Blocking Protein kinase C signaling pathway: mechanistic insights into the anti-leishmanial activity of prospective herbal drugs from Withania somnifera, BMC Genom. source

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    Premisecitation

    Aqueous ethanolic root extract attenuates acute stress-induced gastric ulcerations in rats by affecting a reduction in acid-pepsin levels and an increase in gastric mucin activity.

    “Attenuation of acute stress-”
    • Also stated in: § 6. Conclusions · plain
      “induced gastric ulcerations”
    • Also stated in: § 6. Conclusions · plain
      “reduction in acid -pepsin”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [54] Bhogaonkar, 2006, Ethnopharmacology of Banjara tribe of Umarkhed taluka, district Yavatmal, Maharashtra for reproductive disorders, Indian J. Tradit. Knowl.

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    Premisecitation

    Water-ethanol (7:3) root extract at 500 mg/kg antagonizes hippocampal oxidative stress and prevents changes of major oxidative stress biomarkers.

    “Antagonizes hippocampal”
    • Also stated in: § 6. Conclusions · plain
      “oxidative stress”
    • Also stated in: § 6. Conclusions · plain
      “Prevents changes of major”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [18] Alzoubi, 2019, Withania somnifera root powder protects againist post-traumatic stress disorer-induced memory impairment, Mol. Biol. Rep.

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    Premisecitation

    Withaferin A at 10 mg/kg inhibits eIF4E phosphorylation and protein translation.

    “of eIF4E phosphorylation”
    • Also stated in: § 6. Conclusions · plain
      “and protein translation,”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [293] Ritumala, 2019, Traditional Uses of Plants for Human Use-A Case Study from Kirtinagar Region of Garhwal Himalaya, J. Agric. Technol.

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    Premisecitation

    Withaferin A at 10 mg/kg in a Notch1-mutant T-ALL xenograft in NRG mice causes eIF2A-dependent translation inhibition.

    “eIF2A-dependent”
    • Also stated in: § 6. Conclusions · plain
      “translation inhibition”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [304] Saranraj, 2016, Ethnobotanical survey of medicinal plants from Vellore district, Tamil nadu, India, Int. J. Adv. Res. Biol. Sci. source

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    Premisecitation

    WS2 at doses of 150 and 300 mg/kg suppresses cyclophosphamide-induced potentiation of the DTH reaction.

    “cyclophosphamide-”
    • Also stated in: § 6. Conclusions · plain
      “induced potentiation of”
    • Also stated in: § 6. Conclusions · plain
      “DTH reaction was”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6] Agarwal, 1999, Studies on immunomodulatory activity of Withania somnifera (Ashwagandha) extracts in experimental immune inflammation, J. Ethnopharmacol. source

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    Premisecitation

    Methanolic extract at 0.125-2 mg/ml inhibits acid production, biofilm formation of oral bacteria, and acid tolerance.

    “Inhibited acid production,”
    • Also stated in: § 6. Conclusions · plain
      “biofilm formation of oral”
    • Also stated in: § 6. Conclusions · plain
      “bacteria, and acid”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [253] Parida, P.K., Paul, D., and Chakravorty, D. (2021). Free Energy Landscapes and Residue Network Analysis for Six SARS-CoV-2 Targets in Complex with Plausible Phytochemical Inhibitors from Withania somnifera: 1 µS Molecular Dynamics Simulations (Chemrxiv preprint). source

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    Premisecitation

    Root extract at 500 and 1000 mg/kg b.wt. inhibits proteinuria, TNF-α, nephritis, ROS and NO.

    “Inhibited proteinuria, TNF-”
    • Also stated in: § 6. Conclusions · plain
      “α, nephritis, ROS and NO”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [212] Mirjalili, 2009, Steroidal lactones from Withania somnifera, an ancient plant for novel medicine, Molecules source

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    Premisecitation

    Water extract at 5.0 mg/ml in HepG2 cells increases antioxidant activities compared with control untreated cells.

    “Antioxidant activities”
    • Also stated in: § 6. Conclusions · plain
      “increased; they were”
    • Also stated in: § 6. Conclusions · plain
      “compared with the control”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [13] Ahmed, 2018, Antioxidant activity and apoptotic induction as mechanisms of action of Withania somnifera (Ashwagandha) against a hepatocellular carcinoma cell line, J. Int Med Res source

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    Premisecitation

    WST at 1000 mg/kg and WS2 at 300 mg/kg significantly increase white blood cell counts and platelet counts.

    “A significant increase in”
    • Also stated in: § 6. Conclusions · plain
      “white blood cell counts and”
    • Also stated in: § 6. Conclusions · plain
      “platelet counts”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [6] Agarwal, 1999, Studies on immunomodulatory activity of Withania somnifera (Ashwagandha) extracts in experimental immune inflammation, J. Ethnopharmacol. source

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    Premisecitation

    Root extract at 3 g/day orally in human subjects stabilizes blood glucose levels.

    “Stabilized blood glucose”
    • Also stated in: § 6. Conclusions · plain
      “levels”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [24] Andallu, 2000, Hypoglycemic, diuretic and hypocholesterolemic effect of winter cherry (Withania somnifera, Dunal) root, Indian J. Exp. Biol.

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    • cites [27] Anwer, 2008, Effect of Withania somnifera on insulin sensitivity in non-insulin-dependent diabetes mellitus rats, Basic Clin. Pharm. Toxicol. source

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    Premisecitation

    Water extract significantly decreases TNF-α level.

    “TNF-α level significantly”
    • Also stated in: § 6. Conclusions · plain
      “decreased”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [13] Ahmed, 2018, Antioxidant activity and apoptotic induction as mechanisms of action of Withania somnifera (Ashwagandha) against a hepatocellular carcinoma cell line, J. Int Med Res source

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  • The quote only partly states this claim.

    Premisecitation

    Withaferin-A at 2 μM attenuates p38, ERK-1/2, and C jun JNK.

    “Attenuated p38, ERK-1/2,”
    • Also stated in: § 6. Conclusions · plain
      “C jun JNK”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [148] Kannan, 2016, Ethnomedicinal plants used for Wound Healing purposes by Malayali Tribes of Kalrayan Hills, Salem district, Tamil Nadu, India, Glob. J. Res. Med. Plants Indig. Med.

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    Premisecitation

    Methanolic root extract attenuates proliferative, metastatic and angiogenic signals mediated by IL-8 and cyclooxygenase-2 expression and by arresting the cell cycle in G2/M phase.

    “Attenuation of”
    • Also stated in: § 6. Conclusions · plain
      “proliferative, metastatic”
    • Also stated in: § 6. Conclusions · plain
      “arresting cell cycle in G2/”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [36] Balkrishna, A., Pokhrel, S., Singh, J. and Varshney, A. (2020). 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 (Research Square Preprint). DOI:10.21203/rs-17806/v1. source

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    Premisecitation

    Whole extract activates Nrf2, abrogates apoptosis in an Nrf2-dependent manner, and stimulates phase II detoxification enzymes.

    “Activated Nrf2, abrogated”
    • Also stated in: § 6. Conclusions · plain
      “apoptosis in a Nrf2-”
    • Also stated in: § 6. Conclusions · plain
      “stimulated phase II”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [223] Mohanty, 2016, Withania somnifera Leaf Extract Ameliorates Benzo[a]pyrene-Induced Behavioral and Neuromorphological Alterations by Improving Brain Antioxidant Status in Zebrafish (Danio rerio), Zebrafish source

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    Premisecitation

    Hydro-alcoholic root extract at 50 mg/kg produces myocardial adaptive changes (augmentation of endogenous antioxidants).

    “Produced myocardial”
    • Also stated in: § 6. Conclusions · plain
      “adaptive changes”
    • Also stated in: § 6. Conclusions · plain
      “(augmentation of”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [222] Mohanty, 2015, Herbal folk remedies of Dhenkanal district, Odisha, India, Int. J. Herb. Med.

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    Premisecitation

    Chloroform-methanol root extraction at 20 μg/ml enhances neuronal survival following an in vitro injury that mimics TBI, involving Bax downregulation at the mRNA and protein levels.

    “Enhancement of neuronal”
    • Also stated in: § 6. Conclusions · plain
      “vitro injury that mimics TBI”
    • Also stated in: § 6. Conclusions · plain
      “mRNA and protein levels”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [310] Shah, 2015, Combinations of Ashwagandha leaf extracts protect brain-derived cells against oxidative stress and induce differentiation, PLoS One source

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    Premisecitation

    Withaferin-A at 1.882 μg per mouse (I.V.) inhibits TNF-α and IL-1b.

    “Inhibited TNF-α and IL-1b”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [164] Kuboyama, 2006, Withanoside IV and its active metabolite, sominone, attenuate Abeta(25–35)-induced neurodegeneration, Eur. J. Neurosci. source

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    Premisecitation

    Withaferin A at 12 mg/kg in an A20 allograft in Balb/c mice inhibits HSP90.

    “HSP90 inhibition”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [210] Minhas, 2012, Therapeutic effect of Withania somnifera on pristane-induced model of SLE, Inflammopharmacology source

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    Premisecitation

    Aqueous extract at 200 and 400 mg/kg b.wt./day for 5 weeks blocks the rise in the homeostasis model assessment of insulin resistance and improves the insulin sensitivity index.

    “Blocked the rise in”
    • Also stated in: § 6. Conclusions · plain
      “homeostasis model”
    • Also stated in: § 6. Conclusions · plain
      “insulin sensitivity index”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [375] Umair, 2019, Ethnomedicinal uses of the local flora in Chenab riverine area, Punjab province Pakistan, J. Ethnobiol. Ethnomed. source

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    Premisecitation

    Hydro-alcoholic root extract at 50 mg/kg restores LDH and creatine phosphokinase activity.

    “Restoration of LDH and”
    • Also stated in: § 6. Conclusions · plain
      “creatine phosphokinase”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [222] Mohanty, 2015, Herbal folk remedies of Dhenkanal district, Odisha, India, Int. J. Herb. Med.

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    Premisecitation

    Withaferin A at 10 mg/kg downregulates c-FLIP.

    “downregulation of c-FLIP”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [293] Ritumala, 2019, Traditional Uses of Plants for Human Use-A Case Study from Kirtinagar Region of Garhwal Himalaya, J. Agric. Technol.

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    Premisecitation

    Withanolides (F5 and F6 fractions) at 60 and 15 μg/ml cause apoptosis, externalization of phosphatidylserine and cell cycle arrest, decreased mitochondrial potential, increased ROS, and occurrence of DNA nicks.

    “Apoptosis, externalization”
    • Also stated in: § 6. Conclusions · plain
      “of phosphatidylserine and”
    • Also stated in: § 6. Conclusions · plain
      “occurrence of DNA nicks,”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [67] Chaudhary, 2003, Evaluation of Withania somnifera in a middle cerebral artery occlusion model of stroke in rats, Clin. Exp. Pharmacol. Physiol. source

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    Premisecitation

    Whole extract at 30, 60 and 90 mg/kg/day for 60 days has cardiotropic and cardioprotective effects.

    “Cardiotropic and”
    • Also stated in: § 6. Conclusions · plain
      “cardioprotective”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [246] Panda, 2018, Ethnobotanical study of medicinal plants in Jajpur district of Odisha, India, J. Pharmacogn. Phytochem.

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    • cites [277] Pushpakarani, 2014, Ethnomedicines used by Kaniyakaran tribes in Kaniyakumari district-Southern Western Ghats of Tamil Nadu, India, J. Appl. Pharm. Sci. source

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    Premisecitation

    Aqueous ethanolic root extract at 25 and 50 mg/kg inhibits the significant increase in plasma corticosterone levels induced by CS.

    “Inhibition of the”
    • Also stated in: § 6. Conclusions · plain
      “significant increase in”
    • Also stated in: § 6. Conclusions · plain
      “plasma corticosterone”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [54] Bhogaonkar, 2006, Ethnopharmacology of Banjara tribe of Umarkhed taluka, district Yavatmal, Maharashtra for reproductive disorders, Indian J. Tradit. Knowl.

      Not checked in the free run.

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    Premisecitation

    Fruits of Withania somnifera contain fatty acids, sterols, tocopherols, and hydrocarbons (squalene).

    “Fruits”
    • Also stated in: § 6. Conclusions · plain
      “Fatty acids”
    • Also stated in: § 6. Conclusions · plain
      “Hydrocarbons (squalene)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [44] Bhatia, 2015, Traditional phytoremedies for the treatment of menstrual disorders in district Udhampur, J&K, India, J. Ethnopharmacol. source

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    Premisecitation

    Withania somnifera root extract standard powder enhanced GSH levels in adult Drosophila melanogaster.

    “Enhanced GSH levels”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [206] Marwat, 2008, Ethnophytomedicines for treatment of various diseases in DI Khan district, Sarhad J. Agric.

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    Premisecitation

    Dry leaf powder at 35 mg/250 g BW reduces stress levels.

    “Reduction of stress levels”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [203] Manjunath, 2015, Standardized extract of Withania somnifera (Ashwagandha) markedly offsets rotenone-induced locomotor deficits, oxidative impairments and neurotoxicity in Drosophila melanogaster, J. Food Sci. Technol. source

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    Premisecitation

    An 11:1 extract from Withania somnifera root reduced oxidative stress in transgenic mice carrying G93A sod1 mutant.

    “Reduce oxidative stress”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [97] Elufioye, 2017, Plants-derived neuroprotective agents: cutting the cycle of cell death through multiple mechanisms, Evid. -Based Complement. Altern. Med.: eCAM source

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    • cites [98] Esakkimuthu, 2019, Quantitative analysis of medicinal plants used to treat musculoskeletal ailments by non-institutionally trained siddha practitioners of Virudhunagar district, Tamil Nadu, India, J. Ayurveda Integr. Med. source

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    Premisecitation

    Methanol:Chloroform (3:1) root extract at 0.016-0.25 μg/ml inhibits acetylcholinesterase activity in SK-N-MC cells.

    “| | | | | Internalization of Aβ 1-42 by | Inhibits | |”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [181] Kushwaha, 2021, Phytochemicals present in Indian ginseng possess potential to inhibit SARS-CoV-2 virulence: A molecular docking and MD simulation study, Microb. Pathog. source

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    Premisecitation

    Ethanolic root extract reduces Parkinsonism in mice.

    “| Ethanolic root extract | Parkinsonism | Mice | Increase in striatum dopamine | [306] |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [306] Satoh, 1996, Free radical-independent protection by nerve growth factor and Bcl-2 of PC12 cells from hydrogen peroxide-triggered apoptosis, J. Biochem source

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    Premisecitation

    Glycowithanolides decrease reperfusion-induced changes in mice.

    “| Glycowithanolides | Manage stroke and post-stroke syndromes | Charles-Foster (CF) male | Decrease in reperfusion, hypoperfusion induced | [374] |”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [374] Umair, 2017, An ethnobotanical survey of indigenous medicinal plants in Hafizabad district, Punjab-Pakistan, PLoS One source

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    Premisecitation

    Glycowithanolides decrease hypoperfusion-induced changes in mice.

    “| Glycowithanolides | Manage stroke and post-stroke syndromes | Charles-Foster (CF) male | Decrease in reperfusion, hypoperfusion induced | [374] |”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [374] Umair, 2017, An ethnobotanical survey of indigenous medicinal plants in Hafizabad district, Punjab-Pakistan, PLoS One source

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    Premisecitation

    Root extract reduces ALS/FTLD in hTDP-43 A315T mice.

    “| Root extract | amyotrophic lateral sclerosis (ALS)/ | hTDP-43 A315T mice | depression cluster subscores Decrease in cytoplasmic mislocalization of hTDP-43 | [96] |”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [96] Dwivedi, 2000, Modification of coronary risk factors by medicinal plants, J. Med. Aromat. Plant Sci.

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    Premisecitation

    Standard root extract reduces schizophrenic depression and anxiety in humans.

    “| Standard root extract | Schizophrenic depression and anxiety | Human | Decrease in single item depression, anxiety | [109] |”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [109] Ghatapanadi, 2011, Documentation of folk knowledge on medicinal plants of Gulbarga district, Karnataka, Indian J. Nat. Prod. Resour.

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    Premisecitation

    Root powder reduces PTSD induced memory impairment in rats.

    “| Root powder | PTSD induced memory impairment | Rats | Decrease in PTSD induced oxidative stress | [18] |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [18] Alzoubi, 2019, Withania somnifera root powder protects againist post-traumatic stress disorer-induced memory impairment, Mol. Biol. Rep.

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    Premisecitation

    Aqueous extract of root (Withaferin A) reduces H2O2 and Aβ induced AD in PC12 cells.

    “| Aqueous extract of root | H 2 O 2 and Aβ induced AD | PC12 cells | Increase in cell viability | [172] |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [172] Kumar, 2015, Ethnobatanical study of some common plants from district hamirpur of Himachal Pradesh (India, Int J. Adv. Res

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    Premisecitation

    Aqueous extract of root reduces sleep deprivation effects in rats.

    “| Aqueous extract of root | Sleep deprivation | Rats | Increase in alertness, recognition memory, and | [204] |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [204] Marandi, 2015, Antivenom herbal formulations used against snakebites by the Oroan tribals of Latehar, Jharkhand, World J. Pharm. Res

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    Hydro-alcoholic extract reduces MCA induced cerebral ischemia in male Wistar rats.

    “| Hydro-alcoholic extract | MCA induced cerebral ischemia | Male Wistar rats | Increase in motor functioning | [69] |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [69] Chengappa, 2018, Adjunctive Use of a Standardized Extract of Withania somnifera (Ashwagandha) to Treat Symptom Exacerbation in Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Study, J. Clin. Psychiatry

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    Premisecitation

    Withaferin A reduces 3-NP induced HD in rats.

    “| Withaferin A | 3-NP induced HD | Rats | Increase in free radical scavenging activity | [53,306] |”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [53] Bhattacharya, 2014, Socio-environmental surveys of Tinchuley and Takdah: two emerging ecotourism hamlets of North Bengal, India, Int. Lett. Nat. Sci.

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    • cites [306] Satoh, 1996, Free radical-independent protection by nerve growth factor and Bcl-2 of PC12 cells from hydrogen peroxide-triggered apoptosis, J. Biochem source

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    Premisecitation

    Root extract reduces 3-NP induced HD in rats.

    “| Root extract | 3-NP induced HD | Rats | Decrease in lipid peroxidation and nitrite levels, | [171] |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [171] Kumar, 2014, Glioprotective effects of Ashwagandha leaf extract against lead induced toxicity, BioMed. Res. Int.

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    Premisecitation

    Standard root extract decreases anxiety in humans.

    “| Standard root extract | Schizophrenic depression and anxiety | Human | Decrease in single item depression, anxiety | [109] |”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [109] Ghatapanadi, 2011, Documentation of folk knowledge on medicinal plants of Gulbarga district, Karnataka, Indian J. Nat. Prod. Resour.

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    Premisecitation

    Methanolic root extracts reduce behavioral changes in male Sprague-Dawley rats.

    “| Methanolic root extracts | Behavioral changes | Male Spradue-Dawley rats | Decrease in morphine/ethanol mediated | [40] |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [40] Benjamin, 2019, Heart disease and stroke statistics—2019 update: a report from the American Heart Association, Circulation source

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    Premisecitation

    Root extract reduces stroke induced vasospasm in rats.

    “| Root extract | Stroke induced vasospasm | Rats | Increase in cAMP | [374] |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [374] Umair, 2017, An ethnobotanical survey of indigenous medicinal plants in Hafizabad district, Punjab-Pakistan, PLoS One source

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    Premisecitation

    WSE increases social cognition in humans.

    “| Standard WS extract (WSE) | bipolar disorder | Human (53 patients) | Increase in auditory-verbal working memory, social | [70] |”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [70] Choi, 2015, Withaferin-A inhibits colon cancer cell growth by blocking STAT3 transcriptional activity, J. Cancer Prev. source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S1 (asserted), S3 (load-bearing), S4 (based). The quote only partly states this claim.

    Premisecitation

    WS extract reduces bipolar disorder in humans (60 patients).

    “| WS extract | bipolar disorder | Human (60 patients) | Increase in thyroid function | [108] |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [108] Gauttam, 2013, Development of polyherbal antidiabetic formulation encapsulated in the phospholipids vesicle system, J. Adv. Pharm. Technol. Res source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    WSE decreases symptoms in humans.

    “| Standard WS extract (WSE) | schizophrenia | Human (66 patients) | Decrease in symptoms, stress | [71] |”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [71] Chopra, 2010, Ayurveda–modern medicine interface: A critical appraisal of studies of Ayurvedic medicines to treat osteoarthritis and rheumatoid arthritis, J. Ayurveda Integr. Med. source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    WS extracts decrease glial activation NF-κB phosphorylation in OD1 G93A mice.

    “| WS extracts | frontotemporal lobar degeneration (FTLD) ALS | OD1 G93A mice | Increase in immunomodulatory effect, autophagy, | [97,98] |”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [97] Elufioye, 2017, Plants-derived neuroprotective agents: cutting the cycle of cell death through multiple mechanisms, Evid. -Based Complement. Altern. Med.: eCAM source

      Not checked in the free run.

    • cites [98] Esakkimuthu, 2019, Quantitative analysis of medicinal plants used to treat musculoskeletal ailments by non-institutionally trained siddha practitioners of Virudhunagar district, Tamil Nadu, India, J. Ayurveda Integr. Med. source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    WSE increases auditory-verbal working memory in humans.

    “| Standard WS extract (WSE) | bipolar disorder | Human (53 patients) | Increase in auditory-verbal working memory, social | [70] |”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [70] Choi, 2015, Withaferin-A inhibits colon cancer cell growth by blocking STAT3 transcriptional activity, J. Cancer Prev. source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    WSE decreases stress in humans.

    “| Standard WS extract (WSE) | schizophrenia | Human (66 patients) | Decrease in symptoms, stress | [71] |”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [71] Chopra, 2010, Ayurveda–modern medicine interface: A critical appraisal of studies of Ayurvedic medicines to treat osteoarthritis and rheumatoid arthritis, J. Ayurveda Integr. Med. source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    Standard WS extract (WSE) reduces bipolar disorder in humans (53 patients).

    “| Standard WS extract (WSE) | bipolar disorder | Human (53 patients) | Increase in auditory-verbal working memory, social | [70] |”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [70] Choi, 2015, Withaferin-A inhibits colon cancer cell growth by blocking STAT3 transcriptional activity, J. Cancer Prev. source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    Compound Herbal Preparation (CHP) that includes WS reduces ADHD in human child patients (73 patients).

    “| Compound Herbal Preparation | attention deficit hyperactivity disorder | Human (73 child patients) | Increase in attention, cognition, impulse control | [154] |”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [154] Khan, 2008, Ethnomedicinal uses of Eclipta prostrta Linn, Indian J. Tradit. Knowl.

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    Standard WS extract (WSE) reduces schizophrenia in humans (66 patients).

    “| Standard WS extract (WSE) | schizophrenia | Human (66 patients) | Decrease in symptoms, stress | [71] |”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [71] Chopra, 2010, Ayurveda–modern medicine interface: A critical appraisal of studies of Ayurvedic medicines to treat osteoarthritis and rheumatoid arthritis, J. Ayurveda Integr. Med. source

      Not checked in the free run.

  • The quote only partly states this claim.

    Premisecitation

    WS extract increases thyroid function in humans.

    “| WS extract | bipolar disorder | Human (60 patients) | Increase in thyroid function | [108] |”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [108] Gauttam, 2013, Development of polyherbal antidiabetic formulation encapsulated in the phospholipids vesicle system, J. Adv. Pharm. Technol. Res source

      Not checked in the free run.

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.”
8 of 8

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Opposite Bcl-2 and Bax effects reported for Parkinson's model

    Major

    The text says WS root extract restores Bcl-2 and lowers Bax in the Parkinson's disease model. Table 6 reports a decrease in Bcl-2 and an increase in Bax for root extract neuroprotection, reversing the stated mechanism.

  • Diabetes treatment duration differs between text and table

    Minor

    The discussion gives five days for aqueous extract at 200 and 400 mg/kg. Table 5 gives five weeks for the same doses and extract.

  • Huntington's disease experiment identified as both rats and mice

    Minor

    The discussion identifies the 3-NP Huntington's disease experiment as using male Wistar rats, while Table 6 calls the animals mice for the same cited root-extract study.

  • Sleep-deprivation study alternates between root and leaf extract

    Minor

    The discussion describes the extract in the sleep-deprived-rat study as aqueous root extract. Table 5 identifies the extract for that study, cited as [204], as leaf extract.

  • Conclusion denies clinical stroke drugs after naming one

    Minor

    The conclusion says no clinical drugs are available for treating ischemic stroke patients, whereas the stroke section explicitly names plasminogen activator as a clinically administered drug for ischemic stroke. The narrower claim that no *neuroprotective* drugs are available is consistent, but the conclusion does not retain that qualification.

5 of 5

Cites

Flagged first, then by citations

114 of the 482 references couldn’t be matched to a known paper.

Research works printed but not linked: 46

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  2. Alzoubi, 2019, Withania somnifera root powder protects againist post-traumatic stress disorer-induced memory impairment, Mol. Biol. Rep., 1
  3. Balkrishna, A., Pokhrel, S., Singh, J. and Varshney, A. (2020). 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 (Research Square Preprint). DOI:10.21203/rs-17806/v1. · DOI
  4. Bharat, 1970, 27-deoxy-withaferin from W. somnifera, Acad. Bras. Cienc., 42, 401
  5. Deb, 2014, Traditional Phyto-Therapy with Herbal Compositions Used by Folk-Practitioners of Tripura (North-East) for treatment of various diseases, Indo Am. J. Pharm. Res., 4, 1221
  6. Dhawale, 2015, Ethnomedicinal Survey Of Yavatmal District (MS), Asian J. Pharm. Sci. Technol., 5, 188
  7. Dutta, 2018, Protective effects of Withania somnifera extract in SOD1G93A mouse model of amyotrophic lateral sclerosis, Exp. Neurol., 309, 193, 10.1016/j.expneurol.2018.08.008 · DOI · Paper page
  8. Fahn, 2000, The spectrum of levodopa-induced dyskinesias, Ann. Neurol., 4, 2
  9. Fatima, 2014, Study of traditional ethnoflora used by the bhills of kelwandi region in Ahmednagar district, Maharashtra J. Adv. Appl. Sci. Technol., 1, 25
  10. Gangadharappa, 2018, Ethnomedicinal plants and their utilization by villagers in Koppal district of Karnataka, J. Pharmacogn. Phytochem., 450
  11. Ghosh, 2017, Traditional use of plants against leprosy in India: A review of the recent literature, J. Innov. Pharm. Biol. Sci., 4, 55
  12. Guruprasad, 2013, Indigenous knowledge on medicinal plants among the Iruliga tribal population of Western Ghats areas, Karnataka, India, J. Anthropol., 9, 195
  13. Husain, 2018, Ethnomedicinal significance of two important shrubs, Viz Withania somnifera (L.) and Datura metal (L.) (Family solanaceae) of chhattisgarh, India, Indian J. Sci. Res., 9, 37
  14. Ismail, 2010, Ethnomedicinal survey for important plants of district Lodhran, Punjab, Pakistan, BIOL (E-J. Life Sci.), 1, 52
  15. Kannan, 2016, Ethnomedicinal plants used for Wound Healing purposes by Malayali Tribes of Kalrayan Hills, Salem district, Tamil Nadu, India, Glob. J. Res. Med. Plants Indig. Med., 5, 203
  16. Krishna, 2014, Ethnomedicinal uses of some plant species by tribal healers in Adilabad district of Telangana state, India World J. Pharm. Res., 3, 545
  17. Kumar, 2014, Traditional uses of some medicinal plants of Hamirpur district of Himachal Pradesh for the treatment of diabetes, Int J. Adv. Res, 2, 131
  18. Kumar, 2015, Ethnobatanical study of some common plants from district hamirpur of Himachal Pradesh (India, Int J. Adv. Res, 3, 492
  19. Kumar, 2015, Chem. Pharmacol. Withania somnifera: Update CELLMED, 5
  20. Kumhar, 2017, Enumeration of ethno-medicinal plants of Sidhi district (Madhya Pradesh, Int. J. Bot. Stud., 2, 121
  21. Laddimath, 2016, Ethno-medicinal plants used to treat some psychological (mental) disorders by traditional practitioners of Vijayapur (Bijapur) district of Karnataka, India J. Ethnobiol. Ethnomed., 3, 1
  22. Majeed, 2011, Exploration of ethnomedicinal values of imperative plants of district gujrat, pakistan, Middle-East J. Sci. Res., 7, 397
  23. Majumdar, 1955, Withania somnifera Dunal. Part II: alkaloidal constituents and their chemical characterization, Ind. J. Pharm., 17, 158
  24. Mallick, 2012, Medicinal plants used by the tribals of Ratanpur village of Bankura, West Bengal, Int. J. life Sci., 1, 82
  25. Mallick, 2014, Study of ethnomedicinal values of some shrub in Rourkela steel city and its surroundings, Sundergarh, Odisha, Int J. Appl. Biol. Pharm. Tech., 5, 123
  26. Manikandan, 2013, Ethnomedicinal flora of Ivanur Panchayat in Cuddalore district, Tamil Nadu, India, Int. Res. J. Plant Sci., 3, 39
  27. Marandi, 2015, Antivenom herbal formulations used against snakebites by the Oroan tribals of Latehar, Jharkhand, World J. Pharm. Res, 4, 1971â
  28. Marwat, 2008, Ethnophytomedicines for treatment of various diseases in DI Khan district, Sarhad J. Agric., 24, 305
  29. Mulay, 2012, Plants in child care in Ahmednagar district, Maharashtra (India), Recent Res. Sci. Technol., 4, 11
  30. Patil, 2010, Traditional Medicolore in Badwani District (MP) India, J. Phytol., 2, 49
  31. Qureshi, 2011, Ethnomedicinal uses of plants by the people of Kadhi areas of Khushab, Punjab, Pakistan, Pak. J. Bot., 43, 121
  32. Ramesh, 2019, Ethnomedicinal uses of some medicinal plants collecetd from Amrabad tiger reserve forest, J. Emerg. Technol. Innov. Res., 6, 461
  33. Rani, 2019, Ethanobotanical survey and traditional uses of medicinal plants in jind district of Haryana, India, Plant Arch., 19, 1241
  34. Ritumala, 2019, Traditional Uses of Plants for Human Use-A Case Study from Kirtinagar Region of Garhwal Himalaya, J. Agric. Technol., 6, 42
  35. Shaikh, 2014, Ethnobotanical study of folk medicinal plants used by villagers in Nanded district of Maharashtra (India), Int J. Ayur Herb. Med, 4, 1585
  36. Sharma, 1985, Effects of long-term administration of the roots of ashwagandha and shatavari in rats, Indian Drugs, 29, 133
  37. Sharma, 2014, Comprehensive ethno-botanical survey and cytomorphological status of some important medicinal plants from Himachal Pradesh–A north Indian state, World J. Pharm. Res, 3, 681
  38. Shinwari, 2013, Biological screening of indigenous knowledge based plants used in diarrheal treatment, Pak. J. Bot., 45, 1375
  39. Shivakumar, 2014, Phyto-ethno-medicinal knowledge of folklore people in Kappathgudda Region of Gadaga District, Karnataka, South India, Int J. Sci. Technol., 3, 3080
  40. Singh, 2006, Contribution ofgenomics and proteomics in understanding the role of modifyingfactors in Parkinson’s disease, Indian J. Biochem., 43
  41. Singh, 2007, Pesticides and metalsinduced Parkinson’s disease: involvement of free radicals andoxidative stress, Cell Mol. Biol., 53, 19
  42. Sinkar, 2019, Medicinal plants used for the treatment of various skin disorders by a rural community in Warud Region of Maharashtra, Pharma Innov. J., 8, 791
  43. Sundaram, 2019, Potential of medicinal plants for curing human ailments in Natham, Dindigul district, Tamil Nadu, India, Pharma Innov. J., 8, 512
  44. Uddin, 2012, Phytochemical and pharmacological profile of Withania somnifera Dunal: a review, J. Appl. Pharm. Sci., 2, 170
  45. Vaidyanathan, 2014, Survey of Ethnomedicinal Plants and Folklore Studies On Malayali Tribals Of Vellakadai Village A Part Of Shervaroy Range In Eastern Ghats, Tamil Nadu, Int. J. Recent Sci. Res., 5, 1368
  46. Wagh, 2014, Ethnomedicinal uses of underground plants parts in Jhabua district, Madhya Pradesh, India, Adv. Biol. Res, 8, 151

Cited by

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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
ORCID
Venue
Biomedicine & Pharmacotherapy
Publisher
Elsevier BV
Published
2021-11
Volume
143
Pages
112175
ISSN
0753-3322 (ISSN-L)
DOI
10.1016/j.biopha.2021.112175
OpenAlex
W3202927745
Semantic Scholar
ec84dcb6db4982eddc14b54954dd39a9a43f8c4f
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
Licence
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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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