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胡芦巴种子中分离出的黄酮苷Vicenin-1对实验小鼠的急性和重复剂量(28天)口服毒性研究。

Acute and repeated doses (28 days) oral toxicity study of Vicenin-1, a flavonoid glycoside isolated from fenugreek seeds in laboratory mice.

作者信息

Kandhare Amit D, Bodhankar Subhash L, Mohan V, Thakurdesai Prasad A

机构信息

Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Paud Road, Pune, 411 038, India.

Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Erandwane, Paud Road, Pune, 411 038, India.

出版信息

Regul Toxicol Pharmacol. 2016 Nov;81:522-531. doi: 10.1016/j.yrtph.2016.10.013. Epub 2016 Oct 20.

DOI:10.1016/j.yrtph.2016.10.013
PMID:27773753
Abstract

Vicenin-1 (fenugreek glycoside) has been proven to possess potent anti-inflammatory and anti-oxidant activity. The objective of the present investigation was to determine in-vivo acute and subacute (28-days repeated dose) oral toxicity of Vicenin-1 isolated from fenugreek seed. Vicenin-1 (93%) was isolated from a hydroalcoholic extract of fenugreek seed and characterized using HPLC, TLC, H NMR and C NMR. Acute oral toxicity (AOT) and subacute toxicity studies of Vicenin-1 were carried out according to OECD 425 (up-and-down procedure) and OCED 407 guidelines in Swiss albino mice. In AOT, Vicenin-1 showed 10% mortality when administered at a dose of 5000 mg/kg. However, when vicenin-1 was administered for at doses of 37.5, 75, or 150 mg/kg 28-days it did not show any mortality at the administered doses. Vicenin-1 (75 mg/kg) did not show observational, behavioral, biochemical or histopathological toxic effects. There were minor alterations in body weight, hematology, and histopathology of mice administered with Vicenin-1 (150 mg/kg), but these changes were within normal laboratory ranges. The highest concentration of Venicin-1 was found in liver (3.46%) followed by lung (0.65%). In conclusion, Vicenin-1 showed median lethal dose (LD) of 4837.5 mg/kg with no-observed-adverse-effect levels (NOAEL) at 75 mg/kg and lowest adverse effect levels (LOAEL) at 150 mg/kg for both sexes of mice during AOT and sub-acute toxicity study, respectively.

摘要

鹰嘴豆芽素 -1(胡芦巴糖苷)已被证明具有强大的抗炎和抗氧化活性。本研究的目的是确定从胡芦巴种子中分离出的鹰嘴豆芽素 -1的体内急性和亚急性(28天重复给药)口服毒性。从胡芦巴种子的水醇提取物中分离出鹰嘴豆芽素 -1(93%),并使用高效液相色谱法(HPLC)、薄层色谱法(TLC)、氢核磁共振(H NMR)和碳核磁共振(C NMR)对其进行表征。根据经合组织425号准则(上下法)和经合组织407号准则,在瑞士白化小鼠中进行了鹰嘴豆芽素 -1的急性口服毒性(AOT)和亚急性毒性研究。在急性口服毒性研究中,当以5000毫克/千克的剂量给药时,鹰嘴豆芽素 -1显示出10%的死亡率。然而,当鹰嘴豆芽素 -1以37.5、75或150毫克/千克的剂量给药28天时,在所给药剂量下未显示任何死亡率。鹰嘴豆芽素 -1(75毫克/千克)未显示出观察到的、行为上的、生化或组织病理学毒性作用。给予鹰嘴豆芽素 -1(150毫克/千克)的小鼠在体重、血液学和组织病理学方面有轻微变化,但这些变化在正常实验室范围内。鹰嘴豆芽素 -1的最高浓度在肝脏中被发现(3.46%),其次是肺(0.65%)。总之,在急性口服毒性和亚急性毒性研究中,鹰嘴豆芽素 -1对雌雄小鼠的半数致死剂量(LD)为4837.5毫克/千克,无观察到不良反应水平(NOAEL)为75毫克/千克,最低不良反应水平(LOAEL)为150毫克/千克。

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