Absorption, tissue distribution, tissue metabolism and safety of alpha-mangostin in mangosteen extract using mouse models

Abstract

The commercially available herbal products as the form of extract were usually mixtures containing various compounds. In spite of the purported efficacy in each active constituent, the coexisting constituents in the herbal extract might interfere with the efficacy and safety and affect the pharmacokinetic properties of active constituents. To compare for the pharmacokinetic properties of alpha-mangostin, a major bioactive compound, in mangosteen extract and pure alpha-mangostin, the pharmacokinetics as well as tissue distribution, in vitro metabolism, plasma protein binding and safety evaluation were conducted in mice because a mouse model is required a small amount of compounds and useful to develop disease models. The absorption of alpha-mangostin was increased and hepatic metabolism of alpha-mangostin was decreased in mice treated with mangosteen extract. However, the intestinal metabolism alpha-mangostin is comparable and still extensive in mice treated with alpha-mangostin and mangosteen extract. Intraperitorial LC50 of alpha-mangostin and mangosteen extract was 150 and 231 mg/kg, respectively. These findings may be valuable to explain the different pharmacokinetics and safety of alpha-mangostin and mangosteen extract. Furthermore, these findings are useful to design the efficacy and safety investigation of alpha-mangostin or mangosteen extract in mice with disease models or combination therapies to extrapolate into the clinical levels. (C) 2014 Elsevier Ltd. All rights reserved.