胡椒酸己二醇单酯的降血脂作用及其与牛血清白蛋白相互作用研究

Study on the Anti-hyperlipidemic Activity of 1.6-Hexanediol Piperinic-monoester and Its Interaction with Bovine Serum Albumin

以胡椒碱为起始原料,经水解和酯化反应合成了胡椒酸己二醇单酯,纯度为99.43%,总产率为36.21%,其化学结构经IR、~1HNMR、CNMR、UV和元素分析予以表征。同时建立Wistar大白鼠高脂模型评价降血脂活性,并采用紫外分光光度法和荧光光谱法研究胡椒酸己二醇单酯与牛血清白蛋白(BSA)相互作用。研究结果表明,胡椒酸己二醇单酯显著降低Wistar大白鼠血清中的总胆固醇(TC)水平,显著升高了高密度脂蛋白胆固醇(HDL-C)水平,降低了甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)水平;在模拟生理条件下(pH 7.40),胡椒酸己二醇单酯与牛血清白蛋白形成内源性荧光猝灭,主要为静态猝灭;猝灭常数随温度升高而降低,结合位点数n分别为1.36(25℃)和1.33(37℃);通过热力学参数分析,胡椒酸己二醇单酯与牛血清白蛋白的相互作用是吉布斯自由能降低和熵增加的自发过程,主要是疏水作用力。

Using piperine as the starting material, the unreported 1,6-hexanediol piperinic-monoester was synthesized by hydrolysis and esterification, with a purity of 99.43% and a total yield of 36.21%.Its chemical structure was characterized by IR,~1HNMR,CNMR,UV and elemental analysis.At the same time, a Wistar rat hyperlipidemia model was established to evaluate the antihyperlipidemic activity, and the binding effect of the compound to bovine serum albumin(BSA)was further studied by fluorescence spectroscopy and ultraviolet spectroscopy.The experimental results showed that the compound significantly reduced the level of TC in the serum of high-fat model Wistar rats, significantly increased the level of HDL-C,and decreased the levels of TG and LDL-C.Under the simulated physiological conditions of pH 7.40,the compound formed endogenous fluorescence quenching with BSA,and the main type was static quenching;the quenching constant decreased with the increase of temperature, and the number of binding sites n was 1.36(25 ℃) and 1.33(37 ℃),respectively.Through thermodynamic parameter analysis, the interaction between the compound and BSA was found to be a spontaneous process of Gibbs free energy decrease and entropy increase, and the main force was hydrophobic force.