Berberine In Human And Rat Metabolites

In this paper, we mainly investigated the metabolites of berberine in humans and in rats.Berberine is a quaternary ammonium alkaloid isolated from some clinically-important medicinal plants, including Hydrastis canadensis , Coptis chinensis and et al. Berberine has been demonstrated to have pharmaclogical activities such as antibacteria ,antifungi, antihypertention, antidiabetes, inhibition of ventricular tachyarrhythmias, et al . However berberine's metabolic transformation in humans and animals hitherto is not clear due to its poor absorptivity in gastrointestinal tract. Up to now ,only one literature published in 2002 reported three metabolites isolated from the humans urine after oral administration.Based on survey of published literatures and preliminary test, we decided to study the berberine's metabolites from human urine after oral administration and rat urine after peritoneal injection .Through the polyporous resin column chromatography ,ODS column chromatography, preparative HPLC chromatography , Sephadex LH20 column chromatography, seven metabolites (PUM1-7) were isolated from human urine and two metabolites (RUM 1-2) distinguished from human urine were isolated from rat urine. The structures of nine metabolites were elucidated by1H-NMR, ESI-MS, NOE spectroscopy , and they were Demethy leneberberine-2-O-sulfate (PUM1), Jatrorrhizine-3-O- -D-glucuro nide(PUM2), Thalifendine-10-O-p-D-glucuronide(PUM3), Berberru bine-9-O- -D-glucuronide(PUM4), Jatrorrhizine-3-0-sulfate(PUM5) 3,10-Demethylpalmatine- 10-O-sulfate(PUM6), Columbamine -2-0-p-D-glucuronide (PUM7), Demethyleneberberine-2,3-O- -D-diglucuronide(RUMl), Thalifendine(RUM2), respectively. Among them, six metabolites, PUM2, PUM3, PUM4, PUM6, P UM7, and RUM1 were new compounds.