Abstract
Ganoderic acid D (GD) is the major active triterpenoid in Ganoderma lucidum, a medicinal fungus used daily. However, the metabolic fate of GD remains unknown. To know whether GD is extensively metabolized, we first investigated the metabolism of GD in vitro and in vivo. The metabolic profiles of the bile samples obtained from rats in vivo were almost the same as those obtained in vitro. Using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry, a total of 25 metabolites were identified from the bile sample. Few metabolites were found in the urine samples. These results indicated that biliary rather than renal clearance was the major route of excretion. The major metabolites were identified by comparison with the standard reference compounds. Metabolites at low concentrations were identified by interpreting the mass spectra. Both phase I and phase II metabolites were observed. The metabolic transformation included reduction, monohydroxylation, dihydroxylation, trihydroxylation, oxidation, desaturation, sulfation, and glucuronidation. The main metabolic soft spots in the chemical structure of GD were the 3-carbonyl group, angular methyl groups, the 7-hydroxy group, and the 26-carboxylic acid moiety. Overall, this study gives us an insight into the metabolism of GD, an active oxygenated tetracyclic triterpenoid.
Footnotes
This work was supported by the National Natural Science Foundation of China [Grant 30701077]; the National Science and Technology Major Project “Key New Drug Creation and Manufacturing Program,” China [Grants 2009ZX09308-005, 2009ZX09311-001, 2009ZX09502-020, 2009ZX09304-002]; and the Major Projects of Knowledge Innovation Program of the Chinese Academy of Sciences [Grant KSCX2-YW-R-166].
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
↵ The online version of this article (available at http://dmd.aspetjournals.org) contains supplemental material.
ABBREVIATIONS:
- GD
- ganoderic acid D
- UPLC
- ultra-performance liquid chromatography
- Q-TOF
- quadrupole time-of-flight
- MS
- mass spectrometry
- MDF
- mass defect filter.
- Received July 11, 2012.
- Accepted August 31, 2012.
- U.S. Government work not protected by U.S. copyright
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