Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 66, Issue 46, Pages 12227-12235Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.8b03763
Keywords
norathyriol; pharmacokinetics; bioavailability; metabolism; HPLC-MS/MS
Funding
- National Natural Science Foundation of China [81030065]
- National Natural Science Foundation for Young Scientists of China [81603280]
- Strategic Priority Scientific and Technological Project of Chinese Academy of Science [XDA12040203]
- National Science and Technology Major Project of the Ministry of Science and Technology of China [2018ZX09731016-003, 2018ZX09201001-001-008]
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Norathyriol, an aglycone of mangiferin, is a bioactive tetrahydroxyxanthone present in mangosteen and many medicinal plants. However, the biological fate of norathyriol in vivo remains unclear. In this study, the absorption and metabolism of norathyriol in rats were evaluated through HPLC-MS/MS. Results showed that norathyriol was well absorbed, as indicated by its absolute bioavailability of 30.4%. Besides, a total of 21 metabolites of norathyriol were identified in rats, including methylated, glucuronidated, sulfated and glycosylated conjugates, which suggested norathyriol underwent extensive phase II metabolism. Among those metabolites, 15 metabolites were also identified in hepatocytes incubated with norathyriol, indicating the presence of hepatic metabolism. Furthermore, glucuronide and sulfate conjugates, rather than their parent compound, were found to be the main forms existing in vivo after administration of norathyriol, as implicated by the great increase of exposure of norathyriol determined after hydrolysis with beta-glucuronidase and sulfatase. The information obtained from this study contributes to better understanding of the pharmacological mechanism of norathyriol.
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