11-羟基甘草萜醇类化合物的制备及体外抗氧化活性研究

Preparation and in vitro Antioxidant Activity of 11-hydroxylic Glycyrrhetol Derivatives

为提高甘草次酸(Ib)的抗氧化活性,对其化学结构进行修饰,制备11-羟基甘草萜醇类衍生物。各化合物的抗氧化活性由肝微粒体中的细胞色素P450/NADPH氧化系统做体外抗氧化实验模型进行测定。微粒体中的自由基由探针物DCFH-DA的氧化程度进行检测。维生素E作为阳性对照物。通过还原反应获得甘草萜醇类两种光学异构体———11α-羟基物(2)和11β-羟基物(3)。这两种化合物显示出较强的抗氧化活性,以1.0 mg/mL浓度,分别抑制自由基浓度为50%和51%。相同条件下,先导物Ib和维生素E分别抑制31%和32%的自由基活性。以上结果显示,对先导物Ib的C11位羰基和C30位羧基进行还原修饰,可显著提高其抗氧化活性,这种修饰将能增强先导物对自由基损伤有关病理性病变(如AS)的防治潜能。

Chemical modification was performed to glycyrrhetinic acid（Ib） for improving its antioxidant property. 11- Hydroxylic glycyrrhetol derivativestwo optical isomers-the compounds 2 and 3 were obtained by the reaction of reduction. Their in vitro antioxidant activities were studied using a cytochrome P450/NADPH reductase system from rat liver microsomes. The generation of microsomal free radicals was followed by oxidation of the DCFH-DA probe, while evaluating the capacity to inhibit reactive oxygen species （ROS） formation. The two optical isomers-compounds 2 and 3 exhibited strong antioxidant activities ,and at a concentration of 1.0 mg/mL,they inhibited ROS formation by 50% and 51% , respectively. In the same conditions, the lead compound （Ib） and the reference vitamin E inhibited ROS activity by 31% and 32%. Our results suggested that the chemical reduction of the 11 -keto and 30-carboxyl groups into hydroxyl function can increase the antioxidant activity and anti-atherosclerotic potency of Ib significantly.