Abstract
Bornyl gallate (BG) is a potential drug candidate synthesized by the reaction of two natural products, gallic acid and borneol. Previous studies have strongly suggested that BG is worthy of further investigation due to antioxidant, antiatherosclerosis activities, and obvious activity of stimulating intersegmental vessel growth in zebrafish. This work was designed to elucidate the metabolic profile of BG through analyzing its metabolites in vitro and in vivo by a chromatographic separation coupled with a mass spectrometry. The metabolites of BG were characterized from the rat liver microsome incubation solution, as well as rat urine and plasma after oral administration. Chromatographic separation was performed on an Agilent TC-C18 column (250 mm × 4.6 mm, 5 μm) with gradient elution using methanol and water containing 0.2% (V : V) formic acid as the mobile phase. Metabolites identification involved analyzing the retention behaviors, changes of molecular weights and MS/MS fragment patterns of BG and the metabolites. Five compounds were identified as isomers of hydroxylated BG metabolites in vitro. The major metabolites of BG in rat urine and plasma proved to be BG-O-glucuronide and O-methyl BG-O-glucuronide. The proposed method confirmed to be a reliable and sensitive alternative for characterizing metabolic pathways of BG.
Highlights
Traditional Chinese medicine (TCM), which serves as a resource of bioactive compounds for drug discovery, is attracting increasing global attention [1]
Ionization of the parent drug BG was much better in the negative mode than that in the positive mode, and the difference between the chromatograms of blank samples and those of samples after oral dosing was more noticeable in the negative mode
The daughter ion at m/z 169 was generated due to the McLafferty rearrangement cleavage based on gallic acid group
Summary
Traditional Chinese medicine (TCM), which serves as a resource of bioactive compounds for drug discovery, is attracting increasing global attention [1]. It is generally prescribed as a combination of several herbal species and/or minerals to improve therapeutic effects. Besides the reported antioxidant activity of bornyl gallate [12], previous studies in our laboratory showed that BG has obvious activity of stimulating intersegmental vessel growth in zebrafish and potential for antiatherosclerosis by suppressing monocyte activation and foam cell formation [13] These results strongly suggest that BG is worthy of further investigation. We firstly analyzed the in vitro metabolites of BG after incubating with rat liver microsome (RLM), subsequently investigated the metabolic profiles of BG in rat plasma and urine, and tentatively identified in vivo metabolites by comparing MS/MS fragment patterns and change of molecular mass with those of the parent drug
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