ABSTRACT
Objective: To investigate the pharmacokinetic and pharmacodynamic changes of Yangyin Tongnao Granules (YTG) in cerebral ischemia reperfusion rats after the compatibility of main effective parts (total alkaloids, total flavonoids, total saponins and total phenolic acids). Methods: By using the orthogonal design to research the main effective parts of YTG, nine different dosage ratios combinations were formed, which were used for oral administration in cerebral ischemia reperfusion rats. High performance liquid chromatography-diode array detector (HPLC-DAD) was used to determine the concentration of puerarin, ferulic acid, and ligustrazine in rat plasma at different time points. The non-compartmental model was used to fit the pharmacokinetic parameters by Drug and Statistics (DAS) 3.2.6 software. The total quantum statistical moment analysis method and comprehensive evaluation method were used to evaluate the total pharmacokinetic characteristics. Meanwhile, the content of superoxide dismutase (SOD) and catalase (CAT) were determined by enzyme-linked immunosorbent assay (ELISA) kits. Finally, the PK-PD model and the quantitative equations between drug concentration and efficacy were obtained. Results: The pharmacokinetic characteristics of puerarin, ferulic acid and ligustrazine in cerebral ischemia-reperfusion rats were different. Total statistical moment and comprehensive score study showed that different combinations had different effects on ACUT, mean retention time (MRT), and comprehensive evaluation. The effective parts inhibited the reduction of oxidation indexes such as SOD and CAT. Sigmoid-Emax models were adopted in all PK-PD models, and the fitting results had a good correlation with the measured data. The R values were more than 0.85. Conclusion: Compatibility of YTG activity parts had a certain effect on their pharmacokinetic behaviors and antioxidation in model rats. The total quantum statistical moment analysis and comprehensive evaluation method can be used to study the pharmacokinetics of multi-component traditional Chinese medicine prescriptions. PK-PD model could be used to predict and evaluate the correlation between pharmacokinetics and pharmacodynamics of traditional Chinese medicine prescriptions.
ABSTRACT
Objective: Multi-objectively optimizing the extraction technology for three indicator flavonoids in the formula of Yangyin Tongnao Granules. Methods: Taking the extraction yield of puerarin, calycosin, and formononetin in the formula of Yangyin Tongnao Granules as the detecting indicators, the extraction technology was investigated by 4 factors 3 levels orthogonal test design method. Using R language, combining the entropy weight method to give weight, and establishing the BP neural network model, using the genetic algorithm to target the optimization of network, so as to get the best extraction technology for puerarin, calycosin, and formononetin. Results: The optimization of extraction technology was as follows: ethanol concentration was 85%, extraction time was 1.5 h, extraction temperature was 80℃, and ethanol dosage was 25 times. Under the condition, the predictive value of model comprehensive evaluation was 0.389, the predictive value of the average comprehensive evaluation obtained in the experiment was 0.394, the relative error was 1.27%. So it had a better network prediction. Conclusion: Combining the feasibility and repeatability of the extraction yield and extraction technology for the three index component to establish the mathematical model for analyzing and predicting the extraction technology of puerarin, calycosin, and formononetin in the formula of Yangyin Tongnao Granules and providing a new reference to realize the multi-objective optimization of the extraction technology for the active constituents in Chinese materia medica.