鹰嘴豆中3种异黄酮及其溴乙基化衍生物与胰岛素体外协同降糖活性研究

Synergistic hypoglycemic activity in vitro of three kinds of isoflavone in chickpea and its bromine ethoxylated structure modification and insulin

目的通过对鹰嘴豆中3种异黄酮类化合物染料木素、鹰嘴豆芽素A、刺芒柄花素进行溴乙氧基化结构修饰,研究其对正常Hep G2细胞糖消耗及胰岛素抵抗Hep G2细胞糖消耗的影响及与胰岛素的协同作用。方法对3种异黄酮类化合物进行溴乙氧基化结构修饰,检测其对正常Hep G2细胞糖消耗的影响;建立Hep G2细胞胰岛素抵抗模型作为降糖活性筛选模型,研究衍生物降糖活性,并给予生理胰岛素浓度以研究其之间存在的协同作用。结果合成了4个溴乙氧基化衍生物,其中化合物b具有较好的降糖活性,与阳性药盐酸二甲双胍相比,差异无统计学意义(P>0.05),母体化合物及衍生物与胰岛素均存在协同作用,可明显增加化合物的降糖活性。结论通过溴乙氧基化,获得了降糖活性较好的异黄酮类衍生物,并且可以与胰岛素产生协同作用,为基于中药的创新型降糖药物的研发提供了一定的参考和借鉴。

Objective Through the bromine ethoxylated structure modification of three isoflavones which was genistein,biochanin A,formononetin in chickpea,we studied the influence of glucose consumption of Hep G2 cell and insulin-resistance of Hep G2 cell and the synergistic effect with insulin. Methods The three kinds of isoflavones were modified by the bromine ethoxylated structure modification,and the effect of the glucose consumption of normal Hep G2 cell was detected. We established the insulin-resistance of Hep G2 cell as a screening model for hypoglycemic activity,and studied the hypoglycemic activity of these derivatives,and given the physiological insulin concentration to study the synergistic effect between them. Results Four derivatives of bromine ethoxylated derivatives were synthesized,and the compound B had good hypoglycemic activity,and the difference was not statistically significant（ P〉0. 05） compared with the positive drug metformin hydrochloride. The parent compounds and its derivatives had synergistic effect with the insulin,and could increase the activity of the hypoglycemic activity of the compounds obviously. Conclusion The isoflavone derivatives with good hypoglycemic activity were obtained by the bromine ethoxylated structure modification,and it can be synergistic with insulin. It would provide reference for the research and development of innovative hypoglycemic agents based on traditional Chinese medicine.