PT  - JOURNAL ARTICLE
AU  - Cunqin Jia
AU  - Haiming Shi
AU  - Wei Jin
AU  - Ke Zhang
AU  - Yong Jiang
AU  - Mingbo Zhao
AU  - Pengfei Tu
TI  - Metabolism of Echinacoside, a Good Antioxidant, in Rats: Isolation and Identification of Its Biliary Metabolites
AID  - 10.1124/dmd.108.023697
DP  - 2009 Feb 01
TA  - Drug Metabolism and Disposition
PG  - 431--438
VI  - 37
IP  - 2
4099  - http://dmd.aspetjournals.org/content/37/2/431.short
4100  - http://dmd.aspetjournals.org/content/37/2/431.full
SO  - Drug Metab Dispos2009 Feb 01; 37
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