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-ε-白藜芦醇包封于多层脂质体中:对大鼠药代动力学参数、生物分布和葡萄糖醛酸缀合物形成的影响。

-ε-Viniferin Encapsulation in Multi-Lamellar Liposomes: Consequences on Pharmacokinetic Parameters, Biodistribution and Glucuronide Formation in Rats.

机构信息

INRAE, Bordeaux INP, UR OENOLOGIE, EA 4577, USC 1366, ISVV, Université de Bordeaux, 33140 Villenave d'Ornon, France.

CNRS, Bordeaux INP, CBMN, UMR 5248, Université de Bordeaux, 33600 Pessac, France.

出版信息

Nutrients. 2021 Nov 24;13(12):4212. doi: 10.3390/nu13124212.

Abstract

-ε-viniferin (εVin) is a resveratrol dimer exhibiting promising biological activities for human health. Its bioavailability being low, the development of encapsulation methods would be used to overcome this issue. The aim of this study was to measure the consequences of the encapsulation of εVin in multilamellar liposomes on its pharmacokinetic parameters, metabolism and tissue distribution in rats. After oral administration of εVin (20 mg/kg body weight), either as free or encapsulated forms, plasmas were sequentially collected (from 0 to 4 h) as well as liver, kidneys and adipose tissues (4 h after administration) and analyzed by LC-HRMS. The glucuronide metabolites (εVG) were also produced by hemisynthesis for their quantification in plasma and tissues. The encapsulation process did not significantly modify the pharmacokinetic parameters of εVin itself. However, a significant increase of the T was noticed for εVG after administration of the encapsulated form as compared to the free form. An accumulation of εVin and εVG in adipose tissues was noticed, and interestingly a significant increase of the latter in the mesenteric one after administration of the encapsulated form was highlighted. Since adipose tissues could represent storage depots, and encapsulation allows for prolonging the exposure time of glucuronide metabolites in the organism, this could be of interest to promote their potential biological activities.

摘要

-ε-白藜芦醇二聚体(εVin)具有多种对人类健康有益的生物活性。但其生物利用度低,因此需要开发包封方法来克服这一问题。本研究旨在测量 εVin 包封在多层脂质体中对其在大鼠体内药代动力学参数、代谢和组织分布的影响。大鼠口服给予 εVin(20mg/kg 体重),无论是游离形式还是包封形式,均连续采集血浆(0 至 4 小时)以及肝脏、肾脏和脂肪组织(给药后 4 小时),并通过 LC-HRMS 进行分析。还通过半合成生成葡萄糖醛酸代谢物(εVG),用于定量检测血浆和组织中的 εVG。包封过程并未显著改变 εVin 本身的药代动力学参数。然而,与游离形式相比,包封形式给药后,εVG 的 T 显著增加。在脂肪组织中发现 εVin 和 εVG 的积累,有趣的是,在给予包封形式后,在肠系膜中发现后者的含量显著增加。由于脂肪组织可能是储存库,并且包封可以延长葡萄糖醛酸代谢物在体内的暴露时间,这可能有助于促进其潜在的生物活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30b6/8708455/eaf102c414ee/nutrients-13-04212-g001.jpg

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