RESUMO
BACKGROUND: caffeine is a major constituent in numerous foods, beverages, dietary supplements and medications.Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Sav, and Salvia miltiorrhiza Bunge are traditional medicines commonly used in Asia. OBJECTIVES: to compare the pharmacokinetics of caffeine in humans before and after consuming an aqueous extract of A. dahurica or S. miltiorrhiza, and to propose a mechanistic explanation for in vivo caffeine metabolism inhibition based on in vitro data obtained with human liver microsomes. METHODS: Each of the four human volunteers was given a single oral dose of caffeine before and after consuming an A. dahurica or S. miltiorrhiza extract. Saliva samples were collected from the volunteers at pre-determined time points after receiving caffeine. The saliva samples were analyzed for unchanged caffeine using liquid chromatography. RESULTS: A. dahurica and S. miltiorrhiza extracts were capable of inhibiting caffeine metabolism in the human volunteers. In a separate study, cytochrome (CYP) 1A2-mediated caffeine demethylase activity was studied in incubation containing human liver microsomes, ß-nicotinamide adenine dinucleotide phosphate, and an herbal extract (or a pure bioactive chemical from the herbs). In all cases, CYP1A2 activity was decreased with an increasing inhibitor concentration, confirming the inhibition of caffeine metabolism in vivo. Caffeine metabolism inhibition most likely involved the competitive and/or non-competitive mechanism. CONCLUSION: Because a high level of caffeine in the plasma may result in adverse health effects in humans, care must be exercised when caffeine is consumed together with A. dahurica or S. miltiorrhiza.