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Safety, toxicity and pharmacokinetic assessment of oral Withaferin-A in mice.

التفاصيل البيبلوغرافية
العنوان: Safety, toxicity and pharmacokinetic assessment of oral Withaferin-A in mice.
المؤلفون: Gupta SK; Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India.; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Jadhav S; Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India., Gohil D; Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India.; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Panigrahi GC; Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India.; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Kaushal RK; Department of Pathology, Tata Memorial Hospital, Parel, Mumbai 400012, Maharashtra, India.; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Gandhi K; Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India., Patil A; Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India.; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Chavan P; Composite Laboratory, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India.; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India., Gota V; Department of Clinical Pharmacology, ACTREC, Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India.; Homi Bhabha National Institute, BARC Training School Complex, Anushakti Nagar, Mumbai 400094, Maharashtra, India.
المصدر: Toxicology reports [Toxicol Rep] 2022 May 18; Vol. 9, pp. 1204-1212. Date of Electronic Publication: 2022 May 18 (Print Publication: 2022).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Ireland Ltd Country of Publication: Ireland NLM ID: 101630272 Publication Model: eCollection Cited Medium: Internet ISSN: 2214-7500 (Electronic) Linking ISSN: 22147500 NLM ISO Abbreviation: Toxicol Rep Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [Ireland] : Elsevier Ireland Ltd., [2014]-
مستخلص: Withaferin-A (WA) is the principle component of Withania somnifera (Ashwagandha). It has several biological activities including anti-cancer, anti-diabetic, neuroprotective, hepatoprotective and immune-modulatory properties. The acute and sub-acute toxicity of oral WA was investigated in mice. In the acute toxicity study, up to 2000 mg/kg of WA was well tolerated without any signs of toxicity or death. In the sub-acute toxicity study, mice were orally administered 10, 70 and 500 mg/kg of WA respectively, daily for 28 days. Upon physiological, serum chemistry, hematology and histopathogical examination, no features suggestive of drug-induced toxicity were observed at any dose levels, thereby confirming the No-Observed Adverse Effect Level (NOAEL) to be at least 500 mg/kg. Furthermore, the oral bioavailability of WA was evaluated using single intravenous and oral doses of 10 mg/kg and 70 mg/kg respectively using sparse sampling strategy. Bioanalysis was carried out using a validated LC-MS/MS method. The AUC of WA was found to be 3996.9 ± 557.6 ng/mL*h and 141.7 ± 16.8 ng/mL*h for the intravenous and oral routes of administration respectively. The oral bioavailability was determined to be 1.8%. To conclude, WA was found to be extremely safe even at high doses, with a low oral bioavailability.
Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(© 2022 The Authors.)
References: Cell Biol Toxicol. 2016 Oct;32(5):373-90. (PMID: 27250656)
Int Immunopharmacol. 2020 Jul;84:106575. (PMID: 32416453)
J Pharm Biomed Anal. 2013 Jun;80:203-12. (PMID: 23584079)
Acta Oncol. 1996;35(1):95-100. (PMID: 8619948)
Toxicol Appl Pharmacol. 2015 Dec 1;289(2):297-312. (PMID: 26408225)
Afr J Tradit Complement Altern Med. 2011;8(5 Suppl):208-13. (PMID: 22754076)
Asian Pac J Trop Biomed. 2013 Apr;3(4):253-66. (PMID: 23620848)
Mol Cancer Ther. 2014 Dec;13(12):2930-40. (PMID: 25236891)
J Ovarian Res. 2020 Jul 19;13(1):79. (PMID: 32684166)
J Ayurveda Integr Med. 2020 Jan - Mar;11(1):68-72. (PMID: 30904387)
J Ayurveda Integr Med. 2016 Mar;7(1):30-7. (PMID: 27297507)
Molecules. 2021 Jun 17;26(12):. (PMID: 34204308)
Int J Mol Sci. 2016 Mar 04;17(3):290. (PMID: 26959007)
Altern Med Rev. 2000 Aug;5(4):334-46. (PMID: 10956379)
Int J Mol Sci. 2019 Oct 25;20(21):. (PMID: 31731424)
Front Plant Sci. 2017 Aug 09;8:1390. (PMID: 28848589)
Food Chem Toxicol. 1995 Mar;33(3):223-31. (PMID: 7896233)
Int J Cancer. 1970 Mar 15;5(2):244-52. (PMID: 5449164)
Proc Natl Acad Sci U S A. 2018 Aug 21;115(34):E8096-E8103. (PMID: 30082386)
Biofactors. 2018 Nov;44(6):507-517. (PMID: 30367690)
Cell Death Dis. 2021 Feb 11;12(2):174. (PMID: 33574236)
Nutrients. 2018 Aug 08;10(8):. (PMID: 30096807)
Biomed Pharmacother. 2018 Oct;106:1428-1440. (PMID: 30119216)
Biomed Chromatogr. 2019 Sep;33(9):e4573. (PMID: 31062367)
Biochem Pharmacol. 2020 Mar;173:113602. (PMID: 31404528)
Molecules. 2022 Feb 22;27(5):. (PMID: 35268576)
Phytother Res. 2013 Aug;27(8):1169-78. (PMID: 22996349)
Curr Cancer Drug Targets. 2013 Jul;13(6):640-50. (PMID: 23607597)
فهرسة مساهمة: Keywords: Acute toxicity; No-Observed Adverse Effect Level (NOAEL); Pharmacokinetics; Sub-acute toxicity; Withaferin-A; Withania somnifera
تواريخ الأحداث: Date Created: 20221215 Latest Revision: 20221222
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9742883
DOI: 10.1016/j.toxrep.2022.05.012
PMID: 36518386
قاعدة البيانات: MEDLINE
الوصف
تدمد:2214-7500
DOI:10.1016/j.toxrep.2022.05.012