RESUMO
Scutellaria baicalensis is one of the most widely used herbal medicines in East Asia. Because baicalein and baicalin are major components of this herb, it is important to understand the effects of these compounds on drug metabolizing enzymes, such as cytochrome P450 (CYP), for evaluating herb-drug interaction. The effects of baicalin and baicalein on activities of ethoxyresorufin O-deethylase (EROD), methoxyresorufin O-demethylase (MROD), benzyloxyresorufin O-debenzylase (BROD), p-nitrophenol hydroxylase and erythromycin N-demethylase were assessed in rat liver microsomes in the present study. In addition, the pharmacokinetics of caffeine and its three metabolites (i.e., paraxanthine, theobromine and theophylline) in baicalin-treated rats were compared with untreated control. As results, EROD, MROD and BROD activities were inhibited by both baicalin and baicalein. However, there were no significant differences in the pharmacokinetic parameters of oral caffeine and its three metabolites between control and baicalin-treated rats. When the plasma concentration of baicalin was determined, the maximum concentration of baicalin was below the estimated IC50 values observed in vitro. In conclusion, baicalin had no effects on the pharmacokinetics of caffeine and its metabolites in vivo, following single oral administration in rats.
RESUMO
INTRODUCTION: Numerous drugs and toxicants must be metabolized to an active form. Metabolic activation by host tissues, such as the liver, has been well studied. However, drug and toxicant metabolism by the intestinal microbiota is an unexplored, but essential, field of study in pharmacology and toxicology. The taxonomic diversity and sheer numbers of the intestinal microbiota, and their capacity to metabolize xenobiotics, underscore the importance of this mode of metabolism. AREAS COVERED: Metabolism by the intestinal microbiota has focused on the natural products of glycosides hydrolyzed by intestinal microbiota enzymes, but not by host tissues. Metabolism of synthetic drugs by the intestinal microbiota has been less-intensively investigated. This review provides an overview of xenobiotic metabolism by the intestinal microbiota of both natural products and synthetic drugs. EXPERT OPINION: Metabolism by the intestinal microbiota might result in a different metabolite profile than that produced by host tissues. This could potentially result in either activation or inactivation of the pharmacological and/or toxicological actions of the compound in question. The contribution of the intestinal microbiota to drug metabolism remains relatively unexplored. Therefore, studies of xenobiotic metabolism by the intestinal microbiota need to be included in new drug development as well as classical studies of host tissue metabolism.
