槐角黄酮衍生物制备工艺及其降脂作用研究

Research on preparation technology and lipid-lowering effect of flavonoids derivatives from Fructus Sophorae

目的:通过对槐角的黄酮提取物及其衍生物制备工艺研究,对比药物降脂作用,探索中药创新的研究思路。方法:槐角通过乙醇提取、大孔吸附树脂法得到槐角总黄酮;槐角总黄酮通过酸水解工艺得到槐角总黄酮苷元;再从槐角总黄酮苷元中分离出主要有效成分染料木素,染料木素通过结构修饰得到单体化合物三甲基染料木素;采用高脂血症小鼠模型进行药物降脂活性的对比试验,考察小鼠血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白(LDL-C)和高密度脂蛋白(HDL-C)含量。结果:槐角黄酮提取物及其衍生物各剂量组能明显降低小鼠高脂血症模型中TC、TG与LDL-C的含量,同时升高HDL-C的含量;各剂量组(0. 15 g/kg、0. 3 g/kg、0. 6 g/kg)较模型组均显著降低了小鼠血清TC水平,量效关系明显;各0. 6 g/kg组较模型组均显著降低了小鼠血清TG水平;三甲基染料木素0. 3 g/kg、0. 6 g/kg组和其余0. 6 g/kg组较模型组均显著降低了小鼠血清LDL-C水平;相同剂量下,三甲基染料木素组的效果明显。结论:通过从中药中筛选出有效部位,在有效部位中分离出有效成分,有效成分经过结构修饰而得到疗效更好的药物,这是中药新药创新的一种可行的思路。

Objective: To study the preparation technology and the lipid-lowering effect of flavonoids extract and its derivatives from Fructus Sophorae,and explore the valuable strategy of new development of Traditional Chinese medicine. Methods: The total flavonoids of Fructus Sophorae were obtained by ethanol extraction from Fructus Sophorae and macroporous resin purification. Then the total flavone glycosides of Fructus Sophorae were obtained from the total flavonoids by acid hydrolysis treatment. The main active ingredient genistein was isolated to obtained trimethyl genistein by structure modification. The hyperlipidemic mice model was established for lipid lowering experiment,and serum levels of TC,TG,LDL-C and HDL-C were determined. Results: The contents of TC,TG,LDL-C in hyperlipidemic mice model were significantly decreased and the contents of HDL-C was significantly increased in all groups. Compared with the model group,the serum levels of TC in all dose groups( 0. 15 g/kg,0. 3 g/kg,0. 6 g/kg) were significantly decreased,serum level of TG was significantly decreased in 0. 6 g/kg group,and the serum level of LDL-C was significantly decreased in trimethyl genistein groups at doses of 0. 3 g/kg and 0. 6 g/kg. The trimethyl genistein showed stronger effect than others at the same dose. Conclusions: Purification of active fraction from TCM,isolation of active compound from active fraction,and structural modification of active compound to develop effective drugs is a practical strategy in new TCM R&D.