Effects of Gut Microbiota Modulation on the Oral Pharmacokinetics of Major Components From Guanxinshutong Capsules in Rats
Yihang Lu, Xiaoya Wang, Xinmeng Wang, Yu He, Jiehong Yang, Chang Li, Haitong WanABSTRACT
Background
Guanxinshutong capsule (GXST), derived from Mongolian medicine, is widely used for coronary heart disease. However, the influence of gut microbiota on the bioavailability of its major components remains unknown. This study compared the impact of gut microbiota on the pharmacokinetics of GXST's major components.
Methods
Plasma samples were collected from normal and broad‐spectrum antibiotic (ABX)‐pretreated rats after oral GXST administration. An ultrahigh performance liquid chromatography‐mass spectrometry (UHPLC–MS) method was established and validated (specificity, stability, recovery, and matrix effect) to quantify nine major components. Pharmacokinetic parameters were fitted using a non‐compartmental model.
Results
The validated UHPLC–MS method met analytical criteria. Gut microbiota notably influenced the bioavailability of ellagic acid, ferulic acid, salvianolic acid B, tricin, cryptotanshinone, and tanshinone IIA. Relative bioavailabilities (normal/ABX‐pretreated) were ellagic acid 69.9%, ferulic acid 38.3%, salvianolic acid B 44.3%, tricin 51.6%, cryptotanshinone 144.2%, and tanshinone IIA 81.6%. Notably, the relative bioavailabilities of ferulic acid, salvianolic acid B, and tricin were reduced by approximately 50%.
Conclusions
A sensitive UHPLC–MS method for simultaneous quantification of nine GXST components in rat plasma was validated. These findings provide new insights for pharmacokinetic studies of Traditional Chinese Medicine (TCM) and natural products.