Exploring pharmacokinetics and herb-drug interactions of an herbal extract mixture derived from Poria cocos and Morus alba L.

Abstract

Purpose Poria cocos and Morus alba L., recognized as traditional Chinese medicines (TCMs), have gained attention for their diverse pharmacological effects. An herbal extract mixture (named as NB-02) combining these two botanicals has been developed for the prevention and treatment of Alzheimer's disease (AD). To ensure the efficacy and safety of NB-02, we aimed to evaluate the pharmacokinetic profile and herb-drug interaction potential of the major bioactive compounds, poricoic acid A (PAA) and quinic acid (QA), in NB-02.Methods The plasma concentration profiles of PAA and QA were assessed in rats following oral administration of the extract mixture while evaluating the dose and sex-related pharmacokinetic characteristics. Also, potential herb-drug interactions of the extract mixture were evaluated through cytochrome P450 (CYP) and uridine 5'-diphospho-glucuronosyltransferase (UGT) inhibition assays. P-glycoprotein (P-gp) substrate and inhibitor prediction was conducted in silico.Results A pharmacokinetic study revealed a dose-dependent increase in plasma levels of PAA and QA. PAA exhibited no sex-specificity, whereas QA demonstrated elevated plasma levels in female rats. Furthermore, NB-02 showed no significant inhibitory effects on the activities of both CYP and UGT enzymes. Also, PAA and QA were predicted to be P-gp non-inhibitors.Conclusion The investigation of the pharmacokinetic properties and herb-drug interactions of the major bioactive compounds, PAA and QA, would provide valuable insights into the pharmacological effects and potential clinical application of NB-02.