RT Journal Article
SR Electronic
T1 Metabolism of Echinacoside, a Good Antioxidant, in Rats: Isolation and Identification of Its Biliary Metabolites
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 431
OP 438
DO 10.1124/dmd.108.023697
VO 37
IS 2
A1 Jia, Cunqin
A1 Shi, Haiming
A1 Jin, Wei
A1 Zhang, Ke
A1 Jiang, Yong
A1 Zhao, Mingbo
A1 Tu, Pengfei
YR 2009
UL http://dmd.aspetjournals.org/content/37/2/431.abstract
AB Echinacoside (ECH) is one of the major active phenylethanoid glycosides (PEGs) in famous traditional Chinese medicine, Herba Cistanches. Although it has various bioactivities, such as antioxidation, neuroprotection, and hepatoprotection, knowledge about its metabolic fate is scant. In the present study, eight phase II metabolites, 3,4-O-dimethyl-ECH-3-O-β-d-glucuronide (M1); 4,4-O-dimethyl-ECH-3-O-β-d-glucuronide (M2); 3,4-O-dimethyl-ECH-4-O-sulfate ester (M3); 4,4-O-dimethyl-ECH-3-O-sulfate ester (M4); 3,3-O-dimethyl-ECH (M5); 3,4-O-dimethyl-ECH (M6); 4,3-O-dimethyl-ECH (M7); and 4,4-O-dimethyl-ECH (M8), were isolated from rat bile sample after intravenous administration of ECH and identified by mass spectra and NMR spectroscopy, including 1H NMR, 13C NMR, nuclear Overhauser effect difference spectroscopy, and two-dimensional NMR (heteronuclear single quantum correlation, heteronuclear multiple-bond correlation spectroscopy, gradient-selected correlation spectroscopy, and nuclear Overhauser effect spectroscopy). Among them, M5 to M8 were O-di-methylated conjugates; M1 and M2 and M3 and M4 were O-dimethyl glucuronides and O-dimethyl sulfates, respectively. In the three types of metabolites of rat, the major metabolites were the methyl ethers and the glucuronides, whereas the sulfates were minor. The regioselectivity of conjugation for ECH and metabolic pathway of ECH were proposed, which gave insight into the mechanism of ECH for its bioactivities in vivo. The American Society for Pharmacology and Experimental Therapeutics