Medicinal Chemistry

The Pharmacokinetics and Metabolism of Neomangiferin, a Major Bioactive Component in Anemarrhena asphodeloides

Abstract

Yu Gao, Huihui Liu, Pei Hu, Mingcang Chen, Xiaoting Tian, Zhixiong Li and Chenggang Huang

As a natural derivative of bioactive xanthone mangiferin, neomangiferin exhibits a wide spectrum of bioactivities. However, studies have yet to elucidate the metabolic pathways and pharmacokinetics of orally administered neomangiferin in vivo. In this study, a simple and accurate high-performance liquid chromatography/diode array detector method was developed and validated to simultaneously determine neomangiferin and its active metabolite mangiferin in plasma after oral and intravenous administration of neomangiferin to rats. Chromatographic separation was performed in a C18 column by using water containing 0.1% formic acid-acetonitrile (88:12, v/v) at a flow rate of 0.7 mL/min. The calibration curves of neomangiferin and mangiferin in rat plasma were linear at 150-15000 (r=0.9999) and 50-1500 ng/mL (r=0.9994), respectively. The relative standard deviations of intraday and inter-day precision were below 10.7%, and accuracy ranged from 94.0 to 105.5% for both analytes. Experimental results showed that intravenously and orally administered neomangiferin was partly metabolized into mangiferin. Tmax of neomangiferin and mangiferin was low (0.05 h), and the two components were eliminated at t1/2 of 0.95 and 0.73 h, respectively. Similar to that of mangiferin, the oral bioavailability of neomangiferin was also low (about 0.32%). Thirty-three metabolites were detected and absolutely or tentatively identified on the basis of mass spectral fragmentation pattern and elution order or were confirmed by using available reference standards. Our findings suggested that neomangiferin undergoes rapid and extensive phases I and II metabolic processes, such as deglycosylation, dehydroxylation, methylation, glycosylation, glucuronidation, and sulfation, in rats. In general, the pharmacokinetic and metabolic profiles, including poor bioavailability, high absorption and elimination rates, extensive biotransformation, of neomangiferin are similar to those of mangiferin to some degrees.