葛根黄酮提高桑白皮降糖活性及其机制研究

Effect and Mechanism of Pueraria Flavonoids on Improving Hypoglycemic Effects of Mulberry Root Barks

目的:葛根黄酮(PF)对桑白皮提取物(ME)降糖活性的增效作用研究及其机制探讨。方法:4组大鼠(每组5只)分别灌胃给予含淀粉(2 g.kg-1)的桑白皮提取物(ME,34.5 mg.kg-1)、葛根黄酮(PF,211.5 mg.kg-1)、桑葛复方提取物(ME-PF,250 mg.kg-1)或蒸馏水,给药后于0～2 h内取血测定其血糖水平;另取2组大鼠(每组5只)施行在体单向肠灌流实验,在ME的主要药效成分1-脱氧野尻霉素(1-deoxynojirimycin,DNJ)相同浓度(10μmol.L-1)下以ME或ME-PF进行灌流,以LC-MS/MS法测定灌流液中DNJ的浓度。结果:PF与ME联用时,可显著抑制大鼠餐后血糖水平的升高,与仅给淀粉组比较,2 h内的总血糖血糖浓度-时间曲线下面积(AUC)水平从(8.71±2.26)h.mmol.L-1下降至(5.16±1.42)h.mmol.L-1,其下降幅度达40.8%,而单独使用ME和PF时血糖AUC的下降幅度较小,分别为13.6%[(7,52±1.00)h.mmol.L-1]和11.8%(7.68±2.22 h.mmol.L-1)。肠灌流结果表明,ME-PF中DNJ的平均有效渗透系数Peff值(3.5×10-3)cm.min-1,明显低于单独使用桑白皮的Peff值(7.5×10-3)cm.min-1,(P<0.05);肠吸收率亦有显著差别(P<0.01),分别为14.8%,31.6%。结论:葛根黄酮能显著提高桑白皮提取物降低餐后血糖的作用,这很可能与其抑制桑白皮提取物中DNJ的肠道吸收,从而提高具有α-糖苷酶抑制活性的DNJ的肠道浓度有关。

Objective： The aim of the study was to investigate the effect and its mechanism of pueraria flavonoids （PF） on improving the hypoglycemic effect of mulberry root bark （Morus alba L. ） extract （ME）. Method： Four groups of rats （n = 5 for each） were given with starch （2 g·kg-1） in combination with ME （34.5 mg·kg-1）, PF （2il.5 mg·kg-1）, mixture of ME andPF （ME-PF250mg·kg-1） or water, respectively. 1- deoxynojlrimycin （DNJ） , the main active component of ME for inhibition of a-glycosidase activity, was 20 mg·kg-1 in ME and ME-PF groups. The rat blood glucose levels were assayed in 2 hr after dosing. Another two groups of rats （ n = 5 for each） were used for single-pass small intestinal perfusion of ME and ME-PF, respectively, at DNJ equivalent concentration of 10 umol·kg-1. The DNJ concentrations in perfusion samples w, ere determined by LC- MS/MS methods. Result： When ME was given in combination with PF, the increased blood glucose levels in rats after dosing with starch were significantly depressed. The area under the blood glucose concentration-time curve （AUC） from time 0 to 2 h of rats in ME-PF group was decreased by 40.8% , in comparison with those when given with only starch. While, the AUC in ME and PF groups were decreased by 13.6%, 11.8%, respectively. Intestinal perfusion experiment showed that the transportation rate of DNJ was significantly different （ P 〈 0.05 ） between the two groups ME-PF and ME, with effective permeability （Peii） values of 3.5 ×10 -3, 7.5 × 10 -3 cm2 mln , respectively. The percentage of transportation of DNJ were also significantly different （P 〈 0. 01 ） , with 14.8%, 31.6%, respectively. Conclusion： PF could significantly improve the hypoglyeemic effects of ME, for depress elevation of postprandial blood glucose, this may probably related with that PF could strongly decrease the absorption of DNJ in the small intestine, and resulting higher DNJ concentration in small intestine could display a relative stronger α-glycosidase inhibition activity.