The Study Of Quantitative In Vivo Metabolic Phenomenon Of Scutellarein Group Of Erigeron Breviscapus:Multicompounds Producing Same Metabolites

Objective:To study the quantitative relationship between multi-source normalization in rats and the anti-ischemic stroke activity of protoplasts and metabolites in the scutellaria chinensis group,and to find the true active form of breviscapus in vivo.Methods:?1?Establish LC-MS method for the determination of scutellarin,scutellarein,hispidulin and internal standard quercetin in plasma,brain,liver,kidney and stomach tissue samples?2?Different groups The scutellarin 80 mg/kg,40 mg/kg,20 mg/kg,scutellarin 49.5 mg/kg,breviscapine 40 mg/kg+scutellarein 24.8 Mg/kg,Dengzhanxixin Granules 800 mg/kg?including 80 mg/kg scutellarin?.Pharmacokinetic?PK?parameters were obtained to quantitatively describe the metabolic processes of the compound in the wild scutellarin group.?3?Establish a model of angiogenesis and an antioxidant model of chicken chorioallantoic membrane,evaluate the pharmacological activity of the prototype and metabolites,and the pharmacological activity of the drug combination,and quantitatively describe the pharmacological action intensity of the prototype and metabolites.?4?Construct a PK-PD model to find the interaction between the prototype and the metabolically active concentration and duration of the metabolites and the active ingredients.Result:?1?The linear range of scutellarin,scutellarein and hispidulin in plasma samples was 5-2000 ng/mL?R²>0.99?,and the linear range in brain tissue samples was 25-10000ng/g.?R²>0.99?,in other tissues?liver,kidney,stomach?samples linear range is 50-10000ng/g?R²>0.99?,the LLOQ is 5 ng/mL,25 ng/g,50 ng/g.The precision is less than15%and the accuracy is within 85%-115%.?2?After the administration of breviscapine by intragastric administration,the high concentration?80 mg/kg?was metabolized in the body,and the C_max values of scutellarin,scutellarin and hispidulin in the blood and target organs were 351.89 and 642.79,respectively.,286.80 ng/mL.The administration of scutellarein49.5 mg/kg,breviscapine 40 mg/kg+scutellarein 24.8 mg/kg,the blood concentration of the prototype and metabolites increased slightly,and the half-life side was longer,which was superior to breviscapine.80 mg/kg);breviscapine granules 800 mg/kg administered intragastrically,the half-life of target organs increased,the prototypic bioavailability increased,and the drug was better than breviscapine?80 mg/kg?.?3?The EC₅₀ value of the angiogenesis induced by the chicken embryo chorioallantoic membrane?Scutellaren534.76ng/mL,Scutellarein 193.58 ng/mL,hispidulin 6117.54 ng/mL?.?4?Integrating the PK and PD data,it is difficult to achieve an effective concentration of a single compound,but after the combination of drugs?1:1:1 m/m/m?,the compound of the scutellarein group has a synergistic relationship,when the EC₅₀ value is The CI index value was 0.47 at 203.58ng/mL,and the drug could reach half the effective concentration in the body.Conclusion:The multi-normalization phenomenon of the compound in the scutellarein group can be quantitatively described.The metabolites and prototypes are the main forms in the body.The synergistic effect of the combination of metabolites can be used to determine the metabolic concentration of the drug in the body.