Pharmacokinetic study of Ninjin'yoeito: Absorption and brain distribution of Ninjin'yoeito ingredients in mice

Abstract

Ethnopharmacological relevanceNinjin'yoeito (NYT), a Japanese traditional Kampo medicine, has been reported to exert various clinical benefits such as relief from fatigue, malaise, anorexia, frailty, sarcopenia, and cognitive dysfunction. Recently, some review articles described the pharmacological effects of NYT and additionally indicated the possibility that multiple ingredients in NYT contribute to these effects. However, pharmacokinetic data on the ingredients are essential in addition to data on their pharmacological activities to accurately determine the active ingredients in NYT. Aim of the studyThis study assessed the in vivo pharmacokinetics of NYT using mice. Materials and methodsTarget liquid chromatography–mass spectrometry (LC–MS) and wide target LC–MS or LC–tandem MS of NYT ingredients in plasma and the brain after oral administration of NYT were performed. Imaging MS was performed to investigate the detailed brain distributions of NYT ingredients. ResultsThe concentrations of 13 ingredients in plasma and schizandrin in the brain were quantified via target LC–MS, and the wide target analysis illustrated that several ingredients are absorbed into blood and transported into the brain. Imaging MS revealed that schizandrin was homogenously dispersed in the NYT-treated mouse brain. ConclusionThese results should be useful for clarifying the active ingredients of NYT and their mechanisms of actions.