title: Metabolic profile of 1,5-dicaffeoylquinic acid in rats, an in vivo and in vitro study.
abstract: To explore the metabolism of 1,5-dicaffeoylquinic acid (1,5-DCQA) in rats, liquid chromatography-mass spectrometry in parallel to diode-array detection was used for the rapid detection/characterization of the metabolites formed in bile, urine, and plasma of rats following oral administration of 1,5-DCQA (160 mg/kg). The methylation and glucuronidation of 1,5-DCQA occurring in vitro using rat liver and small intestinal microsomes and cytosols were studied in comparison with those occurring in vivo, and the enzymes involved were also determined. In addition, the anti-HIV (human immunodeficiency virus) activity of three important metabolites was preliminarily evaluated in MT-4 cells infected with HIV-1. A total of 22 metabolites in vivo and in vitro were identified, including four isomeric O-mono-methylated metabolites (M8-M11), nine isomeric O-di-methylated metabolites (M3, M6, M22, and M12-M17), four isomeric O-mono-methyl-glucuronidated metabolites (M2 and M19-M21), four isomeric O-di-methyl-glucuronidated metabolites (M1, M4, M5, and M7), and one glucuronidated metabolite (M18). The O-methylation positions of three important metabolites (M8, M9, and M12) were determined (3''-, 3'-, and 3',3''-) by comparing with synthesized standards. The efficacy experiments showed that M8, M9, and M12 could inhibit HIV replication with IC(50) values of about 25, 25, and 46 microM, respectively. These results suggest that O-methylation and glucuronidation are two important metabolic pathways of 1,5-DCQA, that both rat liver and small intestine can catalyze such reactions by catechol-O-methyltransferase and UDP-glucuronosyltransferases, and that the HIV-1 inhibitory activity of M8, M9, and M12 is comparable to or slightly weaker than that of 1,5-DCQA.
authors.affiliation: Laboratory of Drug Metabolism and Pharmacokinetics, Beijing Institute of Transfusion Medicine, 27 Taiping Road, Beijing 100850, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Zhiyun
authors.initials: Z
authors.lastname: Meng
authors.forename: Junxing
authors.initials: J
authors.lastname: Dong
authors.forename: Liangping
authors.initials: L
authors.lastname: Yan
authors.forename: Libo
authors.initials: L
authors.lastname: Zou
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Tang
authors.forename: Guifang
authors.initials: G
authors.lastname: Dou
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000378:metabolism* / Q000494:pharmacology; D002934:Cinnamates / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019380:Anti-HIV Agents; D002934:Cinnamates; C100257:cynarine