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羟基肉桂酸衍生物对高胆固醇血症的影响:与依泽替米贝的比较——基于Caco-2细胞系的渗透性测定和傅里叶变换红外光谱分析

Hydroxycinnamic acid derivatives effect on hypercholesterolemia, comparison with ezetimibe: Permeability assays and FTIR spectroscopy on Caco-2 ​cell line.

作者信息

Ressaissi Asma, Serralheiro Maria Luísa M

机构信息

Universidade de Lisboa, Faculdade de Ciências, BioISI - Biosystems & Integrative Sciences Institute, Campo Grande, C8, 1749-016, Lisboa, Portugal.

Universidade de Lisboa, Faculdade de Ciências, Departamento de Química e Bioquímica, Campo Grande, 1749-016, Lisboa, Portugal.

出版信息

Curr Res Pharmacol Drug Discov. 2022 May 4;3:100105. doi: 10.1016/j.crphar.2022.100105. eCollection 2022.

Abstract

High blood cholesterol levels may increase the risk of developing atherosclerosis. Since intestinal cholesterol absorption plays a major role in maintaining total body cholesterol homeostasis, the aim of the present study was to compare the effect of ezetimibe and three hydroxycinnamic acid derivatives (rosmarinic acid, chlorogenic acid and m-coumaric acid) that are present in several medicinal plants on cholesterol absorption in the intestinal Caco-2 ​cells. In addition to the permeability assays, studies on alteration of the biochemical properties of Caco-2 ​cells under the effect of ezetimibe and hydroxycinnamic acid derivatives was evaluated using FTIR accompanied with multivariate analysis by PCA. The cholesterol permeability assays showed that these compounds could decrease cholesterol permeability with a percentage ranging from 76.98 to 96.6% with the highest inhibition for ezetimibe. whereas the FTIR studies didn't show similar changes between ezetimibe and the three hydroxycinnamic acid derivatives in protein and nucleic acids region, suggesting that these compounds have hypocholesterolemic effect. Nevertheless, each compound originated a different change on Caco-2 treated cells suggesting a different mode of action.

摘要

高血胆固醇水平可能会增加患动脉粥样硬化的风险。由于肠道胆固醇吸收在维持全身胆固醇稳态中起主要作用,本研究的目的是比较依泽替米贝和几种药用植物中存在的三种羟基肉桂酸衍生物(迷迭香酸、绿原酸和间香豆酸)对肠道Caco-2细胞胆固醇吸收的影响。除了渗透性测定外,还使用傅里叶变换红外光谱(FTIR)并结合主成分分析(PCA)的多变量分析,评估了依泽替米贝和羟基肉桂酸衍生物对Caco-2细胞生化特性改变的研究。胆固醇渗透性测定表明,这些化合物可降低胆固醇渗透性,降低百分比范围为76.98%至96.6%,其中依泽替米贝的抑制作用最强。而FTIR研究表明,依泽替米贝与三种羟基肉桂酸衍生物在蛋白质和核酸区域没有相似的变化,表明这些化合物具有降胆固醇作用。然而,每种化合物对经处理的Caco-2细胞产生了不同的变化,表明其作用方式不同。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca95/9111184/29e02a7d6193/ga1.jpg

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