油橄榄果提取物体外降脂活性成分筛选及作用机制探究

Screening of in vitro lipid-lowering active ingredients from Olea europaea L. fruit extract and preliminary study on the mechanism

中文关键词:  油橄榄果  谱效关系  羟基酪醇  断氧化马钱子苷  分子对接

英文关键词:Olea europaea L. fruit  spectral effect relationship  hydroxytyrosol  secoxyloganin  molecular docking

中文摘要:

      目的 探究油橄榄果提取物体外降脂活性物质基础, 并初步探讨活性成分在体内的降脂作用机制。方法 建立17个油橄榄果提取物样品高效液相色谱(high performance liquid chromatography, HPLC)叠加图谱, 以牛磺胆酸钠结合能力评价各样品的降脂活性, 通过建立样品共有峰与降脂活性的谱效关系, 筛选潜在的降脂活性成分; 并应用计算机虚拟筛选技术预测靶蛋白, 结合分子对接预测其作用靶点, 初步研究其降脂机制。结果 17个油橄榄果提取物样品均具有不同程度降脂能力, 峰P6、P10、P13、P14、P15、P17、P19和P20为潜在的降脂活性成分, 其中P6和P13鉴定为羟基酪醇和断氧化马钱子苷, 二者分别与多不饱和脂肪酸脂氧合酶ALOX15和钠/葡萄糖共转运蛋白1的残基存在氢键、疏水相互作用及静电相互作用, 进而发挥结合抑制作用。结论 油橄榄果提取物中活性成分不仅能通过与牛磺胆酸钠结合, 而且还能与靶蛋白结合发挥降脂作用, 具有多成分、多靶点、多途径的特点, 本研究结果可为后续研究提供理论依据。

英文摘要:

      Objective To explore the active substance basis of in vitro lipid-lowering activity of Olea europaea L. fruit extract, and preliminarily investigate the mechanism of lipid-lowering action of active ingredient. Methods High performance liquid chromatography (HPLC) fingerprints of 17 Olea europaea L. fruit extract samples were established. The lipid-lowering activity of each sample according to the binding ability of sodium taurocholic acid was evaluated. The spectral relationship between the common peaks and lipid-lowering activity was established to screen the potential lipid-lowering active ingredients. Computer virtual screening technology was used to predict the target protein, and molecular docking was used to predict the target of action, and the mechanism of lipid-lowering was preliminarily studied. Results The 17 samples all had different lipid-lowering abilities. The P6, P10, P13, P14, P15, P17, P19 and P20 were potential lipid-lowering active components, and P6 and P13 were identified as hydroxytyrosol and secoxyloganin. They had hydrogen bonding, hydrophobic interaction and electrostatic interaction with residues of polyunsaturated fatty acid lipoxygenase ALOX15 and sodium/glucose cotransporter 1, respectively, and thus exerted binding inhibition. Conclusion The active ingredient in Olea europaea L. fruit extract can not only bind with sodium taurocholate, but also bind with target protein to play a lipid-lowering effect, which has the characteristics of multi-component, multi-target and multi-pathway, the results of this study can provide theoretical basis for subsequent research.