刺梨乙醇提取物对黄嘌呤氧化酶的抑制作用及分子作用机制

Inhibitory effect and molecular mechanism of alcohol extract from Rosa roxburghii Tratt towards xanthine oxidase

以刺梨果实为原料提取刺梨乙醇提取物,利用超高效液相色谱串联质谱(UHPLC-ESI-HRMS/MS)分析刺梨乙醇提取物的主要成分,测定其体外黄嘌呤氧化酶(XOD)的抑制率,并采用分子对接和分子动力学模拟研究其主要成分的可能分子作用机制。结果表明:刺梨乙醇提取物中主要包含有机酸类、多酚类、黄酮类、萜类等化合物,其中刺梨苷2和(-)儿茶素是含量最丰富的成分,分别占干物质总质量的19.64%和8.83%;刺梨乙醇提取物对XOD具有较好的抑制作用,半抑制浓度(IC_(50))为8.17μg/mL;在刺梨乙醇提取物含量较高的成分中,(-)儿茶素与XOD的对接活性较高,分子动力学模拟表明其能通过范德华力、氢键等与XOD多个氨基酸残基相互作用,形成构象稳定的复合物,抑制XOD的活性位点。

The ethanol extract of Rosa roxburghii Tratt analyzed by UHPLC-ESI-HRMS/MS. Meanwhile, the inhibitory effect of the extract towards xanthine oxidase(XOD) Rosa roxburghii Tratt was investigated in vitro. The potential active components and mechanism were investigated by molecular docking and molecular dynamics. The result showed phenolics, flavonoids and terpenoids were the main components in the ethanol extract of Rosa roxburghii Tratt, among which kajiichigoside 2 and(-) catechin were the most abundant components, accounting for 19.64% and 8.83% of dry matter, respectively. The ethanol extract of Rosa roxburghii Tratt had a good inhibitory effect on xanthine oxidase with ICvalue of 8.17 μg/mL. Among the components with higher content of ethanol extract of Rosa roxburghii Tratt,(-) catechin has higher docking activity. Molecular dynamics simulations showed that it could interact with multiple amino acid residues of XOD by van der Waals force and hydrogen bond, forming conformational stable complexes and inhibiting the active site of XOD.