Received for publication April 7, 2008.
Revised August 9, 2008.
Accepted for publication August 11, 2008.

Isolation and Identification of Urinary Metabolites of Berberine in Rats and Humans

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 ODS column chromatography, and preparative high performance liquid chromatography, seven metabolites (HM1-HM7) were isolated from human urine and five metabolites (RM1-RM5) from rat urine following oral administration were isolated.Their structures were elucidated by enzymatic deconjugation and analyses of MS, ¹H-NMR and NOESY spectra. Besides the three known metabolites demethyleneberberine-2-O-sulfate (HM1, RM3), jatrorrhizine-3-O-sulfate (HM5) and thalifendine (RM5), six new metabolites were identified, namely, jatrorrhizine-3-O--D-glucuronide (HM2), thalifendine-10-O--D-glucuronide (HM3), berberrubine-9-O--D-glucuronide (HM4, RM2), 3,10-demethylpalmatine-10-O-sulfate (HM6, RM4), columbamin-2-O--D-glucuronide (HM7), and demethyleneberberine-2,3-di-O--D-glucuronide (RM1). These findings suggest that berberine undergoes a similar biotransformation in rats and humans. Possible metabolic pathways of berberine in rats and humans are proposed.

Key words: metabolite identification, structure elucidation