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
Weitere Informationen

Publikationsverlauf

received Nov. 21, 2009 revised April 22, 2010

accepted May 23, 2010

Publikationsdatum:
14. Juni 2010 (online)

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.

References

  • 1 State Administration of Traditional Chinese Medicine of the People's Republic of China .Zhong Hua Ben Cao. Shanghai; Shanghai Scientific and Technology Press 2006: 525-538
  • 2 Chinese Pharmacopoeia Committee .Pharmacopoeia of the People's Republic of China, Vol. 1. Beijing; Chemical Industry Press 2005: 213-214
  • 3 Duan F J. Prescriptions of Chinese Material Medica. Shanghai; Shanghai Scientific and Technology Press 1995 66 75-76 84
  • 4 Yan D, Jin C, Xiao X H, Dong X P. Antimicrobial properties of berberines alkaloids in Coptis chinensis Franch by microcalorimetry.  J Biochem Biophys Methods. 2008;  70 845-849
  • 5 Iizuka N, Miyamoto K, Okita K, Tangoku A, Hayashi H, Yosino S, Abe T, Morioka T, Hazama S, Oka M. Inhibitory effect of Coptidis Rhizoma and berberine on the proliferation of human esophageal cancer cell lines.  Cancer Lett. 2000;  148 19-25
  • 6 Yokozawa T, Ishida A, Kashiwada Y, Cho E J, Kim H Y, Ikeshiro Y. Coptidis Rhizoma: protective effects against peroxynitrite-induced oxidative damage and elucidation of its active components.  J Pharm Pharmacol. 2004;  56 547-556
  • 7 Yokozawa T, Ishida A, Cho E J, Nakagawa T. The effects of Coptidis Rhizoma extract on a hypercholesterolemic animal model.  Phytomedicine. 2003;  10 17-22
  • 8 Wang Y, Li Z, Liu J, Jiang J D. Berberine is a novel cholesterol-lowering drug working through a unique mechanism distinct from statins.  Nat Med. 2004;  10 1344-1351
  • 9 Yin J, Hu R, Chen M, Tang J, Li F, Yang Y, Chen J. Effects of berberine on glucose metabolism in vitro.  Metabolism. 2002;  51 1439-1443
  • 10 Kong W, Wei J, Abidi P, Lin M, Inaba S, Li C, Wang Y, Wang Z, Si S, Pan H, Wang S, Wu J, Lau C W, Yao X Q, Chen Z Y, Ko W H, Huang Y. Cardiovascular actions of berberine.  Cardiovasc Drug Rev. 2001;  19 234-244
  • 11 Fang X P, Wang T Z, Zhang H, Shuai H, Li D, Xie C K. Quantitative determination of 5 alkaloids in plants of Coptis from China.  Zhongguo Zhong Yao Za Zhi. 1989;  14 33-35 63
  • 12 Huang X P, Li L Y, Qu X Y, Cui G L. Fingerprints of Rhizoma Coptidis from Shizhu by HPLC.  Zhong Yao Cai. 2006;  29 666-669
  • 13 Shen M P, Sun Q, Wang H. Studies on the intravenous pharmacokinetics and oral absorption of berberine HCL in beagle dogs.  Chin Pharmacol Bull. 1993;  9 64-67
  • 14 Yu C, Zhang H, Pan J F, Hong Y C, Ren J Y, Zhu D Y, Xu X R. Determination and preliminary studies of metabolism of berberine in human urine after oral administration.  Chin J Clin Pharmacol. 2000;  16 36-39
  • 15 Zuo F, Nakamura N, Akao T, Hattori M. Pharmacokinetics of berberine and its main metabolites in conventional and pseudo germ-free rats determined by liquid chromatography/ion trap mass spectrometry.  Drug Metab Dispos. 2006;  34 2064-2072
  • 16 Pan J F, Yu C, Zhu D Y, Zhang H, Zeng J F, Jiang S H, Ren J Y. Identification of three sulfate-conjugate metabolites of berberine chloride in health volunteers' urine after oral administration.  Acta Pharmacol Sin. 2001;  21 77-82
  • 17 Zhu M, Han F, Chen H, Peng Z, Chen Y. Identification of palmatine and its metabolites in rat urine by liquid chromatography/tandem mass spectrometry.  Rapid Commun Mass Spectrom. 2007;  21 2019-2022
  • 18 Zhang Y, Wu W, Han F, Chen Y. LC/MS/MS for identification of in vivo and in vitro metabolites of jatrorrhizine.  Biomed Chromatogr. 2008;  22 1360-1367
  • 19 Qiu F, Zhu Z Y, Kang N, Piao S J, Qin G Y, Yao X S. Isolation and identification of urinary metabolites of berberine in rats and humans.  Drug Metab Dispos. 2008;  36 2159-2165
  • 20 Mizuno M, Kojima H, Iinima M, Tanaka T, Goto K. Coumarin derivatives in Coptis trifolia.  Phytochemistry. 1992;  31 717-719
  • 21 Denis B, Ragai K I. Synthesis of flavonoid sulfates: stepwise sulfation of positions 3, 7, and 4′ using N,N′-dicyclohexylcarbodiimide and tetrabutylammonium hydrogen sulfate.  Tetrahedron. 1987;  43 5197-5202
  • 22 Qin H L, Li Z H, Wang P, Yang J R. Establishment of the control substance of plant drug and fingerprints of Coptis chinensis.  Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2004;  26 622-627
  • 23 Tong S, Yan J, Lou J. Preparative isolation and purification of alkaloids from Corydalis yanhusuo W. T. Wang by high speed counter-current chromatography.  J Liq Chromatogr Relat Technol. 2005;  28 2979-2989
  • 24 Chen J, Wang F, Liu J, Lee F S, Wang X, Yang H. Analysis of alkaloids in Coptis chinensis Franch by accelerated solvent extraction combined with ultra performance liquid chromatographic analysis with photodiode array and tandem mass spectrometry detections.  Anal Chim Acta. 2008;  613 184-195

Feng Qiu

Department of Natural Products Chemistry
School of Traditional Chinese Materia Medica
Shenyang Pharmaceutical University Mail Box 81

No. 103 Road WenHua

110016 Shenyang

People's Republic of China

Telefon: + 86 24 23 98 64 63

Fax: + 86 24 23 99 39 94

eMail: fengqiu2000@tom.com