Details

Autor(en) / Beteiligte

• Gupta, Saurabh Kumar
• Jadhav, Shraddha
• Gohil, Dievya
• Panigrahi, Girish Ch
• Kaushal, Rajiv Kumar
• Gandhi, Khushboo
• Patil, Anand
• Chavan, Preeti
• Gota, Vikram

Titel

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

Ist Teil von

• Toxicology reports, 2022, Vol.9, p.1204-1212

Ort / Verlag

Ireland: Elsevier B.V

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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. [Display omitted] •In acute toxicity study Withaferin-A was found to be safe up to 2000 mg/kg.•The observed LD50 of Withaferin-A was > 2000 mg/kg body weight.•Based on repeat dose toxicity 500 mg/kg of Withaferin-A was considered as NOAEL dose.•The oral bioavailability of Withaferin-A was found to be 1.8%.