Metabolites of Protoberberine Alkaloids in Human Urine following Oral Administration of Coptidis Rhizoma Decoction

Yihui Yang; Ning Kang; Hongjun Xia; Jun Li; Lixia Chen; Feng Qiu

doi:10.1055/s-0030-1250053

Planta Medica, Table of Contents

Planta Med 2010; 76(16): 1859-1863
DOI: 10.1055/s-0030-1250053

Pharmacology

Original Papers
© Georg Thieme Verlag KG Stuttgart · New York

Metabolites of Protoberberine Alkaloids in Human Urine following Oral Administration of Coptidis Rhizoma Decoction

Yihui Yang¹ ^, ³ , Ning Kang² , Hongjun Xia¹ , Jun Li¹ , Lixia Chen¹ , Feng Qiu¹

¹Department of Natural Products Chemistry, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical , University, Shenyang, People's Republic of China
²Department of Biochemistry and Molecular Biology, Shenyang Pharmaceutical University, Shenyang, People's Republic of China
³Department of Medicinal and Natural Medicinal Chemistry, Harbin Medical University, Harbin, People's Republic of China

Abstract

Coptidis Rhizoma has been used as a traditional Chinese herbal medicine to treat typhoid, pharyngolaryngitis, diabetes mellitus, gastroenteritis and secretory diarrhea for more than a thousand years in China. However, there is little information on the in vivo chemical constituents of Coptidis Rhizoma following oral administration. In this paper, the alkaloid constituents in urine were studied in humans following oral administration of Coptidis Rhizoma decoction. Using macroporous adsorption resin chromatography, open ODS column chromatography, and preparative high-performance liquid chromatography, twelve protoberberine alkaloid constituents were isolated. Their structures were elucidated by chemical evidence, enzymatic deconjugation and analyses of mass, ¹H‐NMR and NOESY spectra. The identified alkaloid constituents include berberine (P1), groenlandicine 3-O-β-D-glucuronide (M1), dehydrocheilanthifoline 2-O-β-D-glucuronide (M2), thalifendine 10-O-β-D-glucuronide (M3), jatrorrhizine 3-O-β-D-glucuronide (M4), columbamine 2-O-β-D-glucuronide (M5), berberrubine 9-O-β-D-glucuronide (M6), jatrorrhizine 3-O-sulfate (M7), demethyleneberberine 2-O-sulfate (M8), dehydrocorydalmine 10-O-sulfate (M9), 3,10-demethylpalmatine 10-O-sulfate (M10) and 2,3,10-trihydroxyberberine 2-O-sulfate (M11). No other parent protoberberine alkaloids from Coptidis Rhizoma except for a trace of berberine were found in the urine. These findings suggested that the protoberberine alkaloids, which were absorbed in vivo following oral administration of Coptidis Rhizoma decoction, were mainly conjugated with glucuronic acid or sulfuric acid to form phase II metabolites directly or after biotransformation to phase I metabolites, and finally excreted in urine.

Key words

Coptidis Rhizoma - protoberberine alkaloids - metabolites - urine - humans

Full Text

References

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Feng Qiu

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