title: Ultra-performance liquid chromatography and time-of-flight mass spectrometry analysis of ginsenoside metabolites in human plasma.
abstract: American ginseng is a commonly used herbal medicine in the United States. When ginseng is taken orally, its active components, ginsenosides, are reportedly biotransformed by intestinal microbiota. Previous pharmacokinetic evaluations of ginseng in humans have focused on its parent constituents. However, the metabolites, especially those transformed by intestinal microbiota, have not been carefully studied. We used an ultra-performance liquid chromatography/time-of-flight mass spectrometry (UPLC/TOF-MS) method to determine 15 ginsenosides and/or metabolites and their bioavailability in humans. Six healthy human subjects received a single oral dose of 10 g of American ginseng root powder, after which samples of their blood were collected at 0, 2, 4, 7, 9 and 12 h for measurement of ginsenoside/metabolite levels in plasma. Ginsenosides Rb1, Rd, Rg2 and compound K (C-K) were detected in human plasma samples at different time points. The Rb1 concentration peak was 19.90 ± 5.43 ng/ml at 4 h. C-K was detected from 7 h to 12 h with 7.32 ± 1.35 ng/ml at 12 h. Since the last time point was at 12 h, C-K peak level was not observed. The areas under the concentration curves (AUC) from 0 to 12 h were 155.0 ± 19.5 ng⋅h/ml for Rb1 and 26.4 ± 6.4 ng⋅h/ml for C-K, respectively. The gradual decrease of Rb1 levels and the delayed increase in levels of C-K observed in human subjects supported previous reports that enteric microbiota played a key role in transforming Rb1 to C-K.
authors.affiliation: Tang Center for Herbal Medicine Research and Department of Anesthesia and Critical Care, University of Chicago, IL 60637, USA. czwang@dacc.uchicago.edu
authors.forename: Chong-Zhi
authors.initials: CZ
authors.lastname: Wang
authors.forename: Karen E
authors.initials: KE
authors.lastname: Kim
authors.forename: Guang-Jian
authors.initials: GJ
authors.lastname: Du
authors.forename: Lian-Wen
authors.initials: LW
authors.lastname: Qi
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Wen
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.forename: Brent A
authors.initials: BA
authors.lastname: Bauer
authors.forename: Marc B
authors.initials: MB
authors.lastname: Bissonnette
authors.forename: Mark W
authors.initials: MW
authors.lastname: Musch
authors.forename: Eugene B
authors.initials: EB
authors.lastname: Chang
authors.forename: Chun-Su
authors.initials: CS
authors.lastname: Yuan
mesh_terms: D000284:Administration, Oral; D002851:Chromatography, High Pressure Liquid; D005260:Female; D036145:Ginsenosides / Q000008:administration & dosage / Q000097:blood* / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D005894:Panax / Q000737:chemistry*
chemical_list: D036145:Ginsenosides
references.citation: Am J Chin Med. 2010;38(3):485-93
references.pmid: 20503467
references.citation: Curr Drug Metab. 2010 Jan;11(1):1-3
references.pmid: 20307256
references.citation: Drug Metab Dispos. 2009 Dec;37(12):2290-8
references.pmid: 19786509
references.citation: Pharmacol Res. 2010 Mar;61(3):219-25
references.pmid: 19914380
references.citation: Biochem Pharmacol. 1999 Dec 1;58(11):1685-93
references.pmid: 10571242
references.citation: Drug Metab Dispos. 2003 Aug;31(8):1065-71
references.pmid: 12867496
references.citation: J Pharm Pharmacol. 2006 Aug;58(8):1007-19
references.pmid: 16872547
references.citation: Am J Chin Med. 2009;37(6):1139-52
references.pmid: 19938222
references.citation: BMC Complement Altern Med. 2008 Aug 19;8:50
references.pmid: 18713456
references.citation: Biopharm Drug Dispos. 2006 Jan;27(1):39-45
references.pmid: 16302287
references.citation: J Pharm Biomed Anal. 2010 Dec 1;53(4):946-57
references.pmid: 20667431
references.citation: J Pharmacol Sci. 2004 Jun;95(2):153-7
references.pmid: 15215638
references.citation: J Clin Pharmacol. 2008 May;48(5):599-609
references.pmid: 18319359
references.citation: Phytochem Anal. 2008 Sep-Oct;19(5):444-52
references.pmid: 18473328
references.citation: Phytochemistry. 2011 Jun;72(8):689-99
references.pmid: 21396670
references.citation: J Pharm Biomed Anal. 2010 May 1;52(1):66-72
references.pmid: 20079592
references.citation: Adv Food Nutr Res. 2009;55:1-99
references.pmid: 18772102
references.citation: Phytochemistry. 2008 Aug;69(11):2237-44
references.pmid: 18550132
references.citation: Am J Chin Med. 2009;37(6):1179-89
references.pmid: 19938225
references.citation: Am J Chin Med. 2010;38(1):205-18
references.pmid: 20128055
references.citation: Am J Chin Med. 2007;35(4):543-58
references.pmid: 17708622
references.citation: J Chromatogr A. 2009 Mar 13;1216(11):2195-203
references.pmid: 19041979
references.citation: JAMA. 2001 Jul 11;286(2):208-16
references.pmid: 11448284
references.citation: Ann Intern Med. 2004 Jul 6;141(1):23-7
references.pmid: 15238367
references.citation: Nat Prod Rep. 2011 Mar;28(3):467-95
references.pmid: 21258738
references.citation: J Agric Food Chem. 2006 Mar 22;54(6):2261-6
references.pmid: 16536605
references.citation: Am J Chin Med. 2010;38(5):949-60
references.pmid: 20821825