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一种紫薇树皮提取物的体外抗原毒性活性、体内 ADME 预测和对抗黄曲霉毒素 B 诱导的大鼠肝毒性的保护作用。

In vitro antigenotoxic activity, in silico ADME prediction and protective effects against aflatoxin B induced hepatotoxicity in rats of an Erythrina latissima stem bark extract.

机构信息

Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium; Department of Pharmacognosy, Faculty of Pharmacy, Medical University - Sofia, Str. Dunav 2, 1000, Sofia, Bulgaria.

Natural Products & Food Research and Analysis (NatuRA), Department of Pharmaceutical Sciences, University of Antwerp, Universiteitsplein 1, 2610, Antwerp, Belgium.

出版信息

Food Chem Toxicol. 2020 Jan;135:110768. doi: 10.1016/j.fct.2019.110768. Epub 2019 Aug 31.

Abstract

Stem bark of Erythrina latissima E. Mey (Leguminosae) contains a wide range of prenylated flavonoids able to counteract the genotoxic properties of aflatoxin B (AFB). Thus, the hypothesis was raised that E. latissima stem bark extracts (ELBE) may counteract the in vivo hepatotoxic effects of aflatoxins, contaminants in food and feed. An HPLC-DAD method was developed and validated to determine the level of flavonoid aglycones (11.82%) and glycosides (16.17%). ADME, pharmacokinetic and drug-likeness assessment of major flavonoids of ELBE, using the web tool SwissADME, showed good oral bioavailability. The protective effect of ELBE against AFB induced genotoxicity in the Vitotox assay after metabolic activation was confirmed (IC of 44.32 μg/ml), followed by evaluation of its inhibitory effect on hepatotoxicity in rats induced by the same agent. Male Wistar rats were orally treated with ELBE (20 mg/kg, 50 mg/kg and 100 mg/kg) or curcumin (500 mg/kg) combined with piperine (20 mg/kg) - positive control, for 8 days prior to AFB exposure (1 mg/kg). The ELBE group showed a decreased activity of ALP and γ-GT compared to the AFB group. Histopathological examination of the liver demonstrated ameliorative effects of ELBE. Thus, ELBE could have a protective effect against hepatotoxins such as AFB.

摘要

厚叶木豆(Erythrina latissima E. Mey)的茎皮含有广泛的类异戊二烯黄酮,能够对抗黄曲霉毒素 B(AFB)的遗传毒性。因此,提出了厚叶木豆茎皮提取物(ELBE)可能对抗食品和饲料中污染物黄曲霉毒素体内肝毒性作用的假说。开发并验证了一种 HPLC-DAD 方法来测定类黄酮苷元(11.82%)和糖苷(16.17%)的水平。使用 SwissADME 网络工具对 ELBE 中的主要类黄酮进行 ADME、药代动力学和类药性评估,显示出良好的口服生物利用度。在 Vitotox 测定中,经过代谢激活后,ELBE 对 AFB 诱导的遗传毒性的保护作用得到了证实(IC 为 44.32μg/ml),随后评估了其对同一药物诱导的大鼠肝毒性的抑制作用。雄性 Wistar 大鼠在 AFB 暴露(1mg/kg)前 8 天,经口给予 ELBE(20mg/kg、50mg/kg 和 100mg/kg)或姜黄素(500mg/kg)联合胡椒碱(20mg/kg)-阳性对照。与 AFB 组相比,ELBE 组的 ALP 和 γ-GT 活性降低。肝组织病理学检查显示 ELBE 具有改善作用。因此,ELBE 可能对 AFB 等肝毒素具有保护作用。

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