The Primary Study Of The Compatibility Rule In Vivo Of Coptidis Rhizoma Based On Its Hypoglycemic Activity

The compatibility of Coptidis rhizoma significantly improves the metabolism disorder of blood glucose,blood lipid and insulin.However,its compatibility rule remains unclear.Therefore,this research selects Jinqijiangtang tablet as subject.Re-combining Coptidis rhizoma,Astragali radix and Lonicerae Japonicae flos and selecting prediabetes as disease model,the compatibility rule between Coptidis rhizoma,Astragali radix and Lonicerae Japonicae flos in vivo is primarily investigated at aspect of pharmacokinetics and pharmacodynamics.Meanwhile,this research performs a primary exploration about the activities of gingerols in Zingiberis rhizoma towards mitochondria thermogenesis,which makes a foundation of compatibility rule of Coptidis rhizoma and Zingiberis rhizoma at aspect of mitochondria energy metabolism.The main content of our study are as follows:1.The compatibility rule of Coptidis rhizoma,Astragali radix and LoniceraeJaponicae flos in vivo based on pharmacokinetics.Pharmacokinetics is able to reflect the metabolism rule in vivo of drugs.We re-combined the three ingredients in Jinqijiangtang tablet into three groups including Coptidis rhizoma,Astragali radix-Lonicerae Japonicae flos?huangjin group?and Coptidis rhizoma-Astragali radix-Lonicerae Japonicae flos?huangjinlian group?.And prediabetes characterized by insulin metabolism disorder and impaired glucose tolerance was selected as disease model.UPLC-API-MS/MS was applied to determine the contents of representative components in Astragali radix and Lonicerae Japonicae flos to investigate the role of Coptidis rhizoma in pharmacokinetic behavir of Astragali radix and Lonicerae Japonicae flos.By analyzing the pharmacokinetic parameters of 5analysts in Astragali radix and Lonicerae Japonicae flos,it was found that for astragaloside IV,its C_max decreased,T_max increased,AUC_0?t?t increased and T_1/2/2 increased,which means the absorption and elimination of astragaloside IV were accelerated and its absorption degree was increased by Coptidis rhizoma.For formononetin,its T_maxax increased,AUC_0?t?t decreased and T_1/2/2 decreased,which means absorption of formononetin was decelerated,absorption degree was decreased and elimination was accelerated by Coptidis rhizoma.For chlorogenic acid,its C_max decreased,T_maxax increased,AUC_0?t decreased and T_1/2/2 increased,which means Coptidis rhizoma decelerated both absorption and elimination of chlorogenic acid.For caffeic acid,its C_max decreased,T_max increased,AUC_0?t increased and T_1/2/2 increased,which means Coptidis rhizoma decelerated the absorption and elimination but increased the absorption degree of caffeic acid.For luteoloside,its C_max decreased,T_max increased,AUC_0?t decreased and T_1/2/2 increased,which means the absorption rate,absorption degree and elimination of luteoloside were all decreased by Coptidis rhizoma.2.The pharmacodynamic study of activities of Coptidis rhizoma,Astragali radix andLonicerae Japonicae flos on glucose,lipid and insulin metabolism in prediabetes.Only the single use of Coptidis rhizoma could obviously reduce the fasting blood glucose?P<0.05?.Huangjin group and huangjinlian group had lower fasting blood glucose than model group without significant difference.Meanwhile,the serum insulin and HOMA-IR in huangjinlian group was the lowest?P<0.05?,indicating that the combination of Coptidis rhizoma,Astragali radix and Lonicerae Japonicae flos is more beneficial for the use of insulin,promotion of peripheral insulin sensitivity and improvement of insulin resistance.Moreover,three administration forms could reduce serum triglyceride and free fatty acid?P<0.05?.And liver pathology inspection showed that the combination of Coptidis rhizoma,Astragali radix and Lonicerae Japonicae flos exerted the best effect on relieving the fat accumulation in liver.3.The activity of gingerols on mitochondria thermogenesis based on microcalorimetryWith microcalorimetry and pricinpal component analysis,it was found that 6-gingerol,8-gingerol and 6-shogaol all exhibited the role of elevation on mitochondria heat production.In conclusion,this research investigated the intervention of Coptidis rhizoma on pharmacokinetic behavior of components in Astragali radix and Lonicerae Japonicae flos and the therapeutic effects before and after compatibility towards prediabetes.Finally,a primary exploration about gingerols on mitochondria thermogenesis was performed.This research provides a reference for the research about compatibility rule of Coptidis rhizoma in vivo and mechanism underlying diabetes treatment in compatibility at aspect of mitochondria energy metabolism.