J Agric Food Chem. 2018 Apr 11;66(14):3700-3707. doi: 10.1021/acs.jafc.8b00373. Epub 2018 Mar 28.
Grape seed extract contains a high content of proanthocyanidins that can be depolymerized into C-4-substituted (epi)catechin derivatives in the presence of nucleophiles. However, the biological and medicinal values of depolymerization products have been rarely investigated. Recently, we developed a novel depolymerization product (-)-epicatechin-4β- S-captopril methyl ester (ECC) derived from the reaction of grape seed proanthocyanidin extract with captopril in the presence of acidified methanol. A central composite design was employed to select the most appropriate depolymerization temperature and time to obtain the target product ECC with a high yield. A total of 16 metabolites of ECC in rat urine, feces, and plasma were identified using liquid chromatography quadrupole time-of-flight tandem mass spectrometry. The in vivo results suggested that ECC could release captopril methyl ester and epicatechin, followed by the generation of further metabolites captopril and epicatechin sulfate conjugates. Therefore, ECC may be used as a potential prodrug with synergistic or additive hypotensive effects.
葡萄籽提取物含有丰富的原花青素，在亲核试剂存在下可以解聚为 C-4 取代（表）儿茶素衍生物。然而，解聚产物的生物学和药用价值很少被研究。最近，我们开发了一种新型的解聚产物（-）-表儿茶素-4β-S-卡托普利甲酯（ECC），它是由葡萄籽原花青素提取物在酸化甲醇存在下与卡托普利反应得到的。采用中心复合设计选择最合适的解聚温度和时间，以获得高产率的目标产物 ECC。使用液相色谱四极杆飞行时间串联质谱法鉴定了大鼠尿、粪和血浆中 ECC 的 16 种代谢物。体内结果表明，ECC 可释放卡托普利甲酯和表儿茶素，随后生成进一步的代谢物卡托普利和表儿茶素硫酸酯缀合物。因此，ECC 可能作为一种具有协同或相加降压作用的潜在前药。
