Abstract
The urinary metabolites of berberine, an isoquinoline alkaloid isolated from several Chinese herbal medicines, were investigated in rats and humans. Using macroporous adsorption resin chromatography, open octadecyl silane column chromatography and preparative high-performance liquid chromatography, we isolated seven metabolites (HM1-HM7) from human urine and five metabolites (RM1-RM5) from rat urine after oral administration. Their structures were elucidated by enzymatic deconjugation and analyses of mass spectrometry, 1H NMR, and nuclear Overhauser effect spectroscopy spectra. Besides the three known metabolites demethyleneberberine-2-O-sulfate (HM1 and RM3), jatrorrhizine-3-O-sulfate (HM5), and thalifendine (RM5), six new metabolites were identified, namely, jatrorrhizine-3-O-β-d-glucuronide (HM2), thalifendine-10-O-β-d-glucuronide (HM3), berberrubine-9-O-β-d-glucuronide (HM4 and RM2), 3,10-demethylpalmatine-10-O-sulfate (HM6 and RM4), columbamin-2-O-β-d-glucuronide (HM7), and demethyleneberberine-2,3-di-O-β-d-glucuronide (RM1). These findings suggest that berberine undergoes similar biotransformation in rats and humans. Possible metabolic pathways of berberine in rats and humans are proposed.
Footnotes
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This study was supported by the Educational Foundation of Liaoning Province (20060877) and the Science and Technology Foundation of Shenyang (1063306-1-00).
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doi:10.1124/dmd.108.021659.
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ABBREVIATIONS: HPLC, high-performance liquid chromatography; ODS, octadecyl silane; EtOH, ethanol; MeOH, methanol; ESI, electrospray ionization; DMSO-d6, deuterated dimethyl sulfoxide; MS, mass spectrometry; NOESY, nuclear Overhauser effect spectroscopy; LC/MSn, liquid chromatography-mass spectrometry at stage n.
- Received April 6, 2008.
- Accepted August 11, 2008.
- The American Society for Pharmacology and Experimental Therapeutics
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