Short Chain (≤C4) Esterification Increases Bioavailability of Rosmarinic Acid and Its Potency to Inhibit Vascular Smooth Muscle Cell Proliferation.
Short Chain (≤C4) Esterification Increases Bioavailability of Rosmarinic Acid and Its Potency to Inhibit Vascular Smooth Muscle Cell Proliferation.
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短链（≤C4）酯化增加了马沙林酸的生物利用度及其抑制血管平滑肌细胞增殖的效力。
DOI：
10.3389/fphar.2020.609756
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发表时间：
2020
影响因子：
5.6
通讯作者：
Liu R
中科院分区：
文献类型：
--
作者：
Blažević T;Reznicek G;Ding L;Yang G;Haiss P;Heiss EH;Dirsch VM;Liu R
迷迭香酸是一种天然酚酸和活性化合物，存在于许多烹饪植物中，如迷迭香、薄荷、罗勒和紫苏。为了改善迷迭香酸的药代动力学特征及其对血管平滑肌细胞增殖的活性，我们产生了一系列具有从C1至C12的增加的烷基链长度的迷迭香酸酯。大鼠血液样品的UHPLC-MS/MS分析显示，口服迷迭香酸丁酯后，迷迭香酸的生物利用度增加最高，高达10.52%，而迷迭香酸以其原始形式给药后仅为1.57%。当在体外添加到血管平滑肌细胞中时，所有迷迭香酸酯都被吸收，保持酯化并抑制血管平滑肌细胞增殖，随着烷基链长度增加到C4，IC 50值下降，迷迭香酸丁酯的IC 50为2.84 µM，如刃天青试验中所示。血管平滑肌细胞被阻滞在细胞周期的G 0/G1期，视网膜母细胞瘤蛋白磷酸化被阻断。与较长烷基链的酯化没有改善吸收，并在体外环境中导致细胞毒性。在这项研究中，我们证明了与适当长度的烷基链（C1-C4）的酯化是一种有前途的方法，以提高迷迭香酸在大鼠体内的生物利用度和在大鼠血管平滑肌细胞的体外生物活性。
Rosmarinic acid is a natural phenolic acid and active compound found in many culinary plants, such as rosemary, mint, basil and perilla. Aiming to improve the pharmacokinetic profile of rosmarinic acid and its activity on vascular smooth muscle cell proliferation, we generated a series of rosmarinic acid esters with increasing alkyl chain length ranging from C1 to C12. UHPLC-MS/MS analysis of rat blood samples revealed the highest increase in bioavailability of rosmarinic acid, up to 10.52%, after oral administration of its butyl ester, compared to only 1.57% after rosmarinic acid had been administered in its original form. When added to vascular smooth muscle cells in vitro, all rosmarinic acid esters were taken up, remained esterified and inhibited vascular smooth muscle cell proliferation with IC50 values declining as the length of alkyl chains increased up to C4, with an IC50 of 2.84 µM for rosmarinic acid butyl ester, as evident in a resazurin assay. Vascular smooth muscle cells were arrested in the G0/G1 phase of the cell cycle and the retinoblastoma protein phosphorylation was blocked. Esterification with longer alkyl chains did not improve absorption and resulted in cytotoxicity in in vitro settings. In this study, we proved that esterification with proper length of alkyl chains (C1–C4) is a promising way to improve in vivo bioavailability of rosmarinic acid in rats and in vitro biological activity in rat vascular smooth muscle cells.
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影响因子：
5.4
作者：
Qiang, Zhiyi;Ye, Zhong;Hauck, Cathy;Murphy, Patricia A.;McCoy, Joe-Ann;Widrlechner, Mark P.;Reddy, Manju B.;Hendrich, Suzanne
通讯作者：
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影响因子：
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作者：
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通讯作者：
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通讯作者：
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作者：
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通讯作者：
Rollins, BJ
影响因子：
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作者：
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通讯作者：
Kastrati, Adnan