Analysis Of Multi-compounds In Jinqi Jiangtang Tablets And Its Effect On The Pharmacokinetics Of Metformin In Diabetic Mice

Purpose: In this study we qualitatively and quantitatively analyzed multi-compounds of Jinqi Jiangtang Tablets(JQJTT)in vivo and in vitro.Moreover,we explored the pharmacokinetic effects of JQJTT on metformin in diabetic mice.This study established a more comprehensive method for the quality control of JQJTT and could provide an experimental basis for the combination of JQJTT and metformin.Methods:(1)An LC-LCQ MS method was used to analyze 21 compounds in the extract of JQJTT.(2)The mice were fed with high fat diet(HFD)and then intraperitoneally injected with freshly prepared streptozocin(STZ)to induce type 2 diabetes.The compounds in diabetic mice plasma and liver after oral administration of JQJTT were qualitatively analyzed by LC-LTQ-Orbitrap MS.(3)The type 2 diabetic mice were orally administered metformin(80 mg/kg)with or without JQJTT(2.5 g/kg)for 2 weeks.The concentration of metformin in the plasma,tissues,urine and bile samples were analyzed by an LC-MS/MS method.The pharmacokinetic parameters were calculated by Win Non Lin software.Non-everted intestinal sac and transfected cell model were used to explain the influence mechanisms of JQJTT on metformin.The SPSS 21.0 statistics software was used in statistical analysis.Result:(1)We developed an LC-LCQ MS method to simultaneously determine the contents of 21 compounds in JQJTT.The validation results of the method were within the requirements of content determination.The content of berberine was highest in the extract of JQJTT,followed by chlorogenic acid.(2)It was found that the mice in model group showed insulin resistance and higher fasting blood glucose(FBG)which was greater than 11 mmol/L.56 compounds were qualitatively identified in the extract of JQJTT.22 compounds and 21 compounds were qualitatively identified in type 2 diabetic mice plasma and liver,respectively.(3)Pharmacokinetic study showed that JQJTT can significantly decreased the concentration of metformin in type 2 diabetic mice plasma,liver,keletal muscle,kidney,intestine,fat,urine and bile samples.In vitro experiments showed that JQJTT can significantly inhibited the absorption of metformin in duodenum.The alkaloids(berberine,palmatine,jatrorrhizine,and coptisine)in JQJTT can significantly inhibited the transport of metformin in r Oct1-MDCK and r Mate1-MDCK cell lines.Conclusion: A quantitative analysis method for 21 compounds in the extract of JQJTT was established,which provided a more comprehensive method for the quality control of JQJTT.The various compounds in plasma and liver of JQJTT could affect the pharmacokinetic characteristics of metformin.The mechanism is mainly due to inhibition of r Oct1-MDCK and r Mate1-MDCK-mediated transport of metformin.