Pharmacokinetic study of Yindan Xinnaotong soft capsule after oral administration in rats and its network pharmacology-based analysis on cardiovascular diseases

Abstract

Abstract Background Yindan Xinnaotong soft capsule (YDXNT) is a Chinese herbal preparation, which was used to treat coronary disease, angina, hyperlipidemia and stroke in the clinic. The chemical ingredients of YDXNT have been investigated, but the pharmacokinetic study of the absorbed components of YDXNT and the exploration of their effect on cardiovascular diseases (CVD) are still insufficient. Method A sensitive and accurate quantitative method based on ultra-high performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-QQQ MS) was established and validated, which was then applied to the pharmacokinetic study of the potential active compounds in the plasma of rats after oral administration of YDXNT. Then the measured analytes were regarded as effective compounds and their potential targets and mechanism of action were predicted after the construction and analysis of compound-target network of YDXNT and CVD. Results The UHPLC-MS based quantitative method was verified to have acceptable linearity, specificity, accuracy, precision, matrix effect, extract recovery and stability for pharmacokinetic analysis, and 15 absorbed compounds in rat plasma after oral administration of YDXNT was studied. Different types of compounds showed various pharmacokinetic characteristics, for instance, ginkgolides with higher maximum plasma concentration (Cmax), flavonoid presenting concentration-time curve with double peaks, phenolic acids with shorter time to reach maximum plasma concentration (Tmax), saponins with long elimination half-life (t1/2) and tanshinones showing fluctuant plasma concentration. Then a network pharmacology-based analysis indicated that those potential active compounds of YDXNT interacted with targets such as MAPK1 and MAPK8, and intervened in the MAPK signaling pathway to display its therapeutic effect on CVD. Conclusion The pharmacokinetics combined network pharmacological analysis provides the potential pharmacological compounds and their integrating mechanism of YDNXT against CVD.