RT Journal Article
SR Electronic
T1 Chemoenzymatic Preparation of Silybin β-Glucuronides and Their Biological Evaluation
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1513
OP 1517
VO 28
IS 12
A1 Kr̆en, Vladimír
A1 Ulrichová, Jitka
A1 Kosina, Pavel
A1 Stevenson, David
A1 Sedmera, Petr
A1 Přikrylová, Věra
A1 Halada, Petr
A1 šsimánek, Vilím
YR 2000
UL http://dmd.aspetjournals.org/content/28/12/1513.abstract
AB Chemoenzymatic glucuronidation of the optically pure silybin A (1) using ovine liver glucuronyl transferase afforded three β-glucuronides of silybin, substituted at phenolic OH groups at the positions C-20 (2), C-7 (3), and C-5 (4) formed in the yields 27, 62.5, and 2.5%, respectively. Using these standards, it was shown that the main silybin conjugate in humans is its 20-β-d-glucuronate (2), while the C-7 regioisomer (3) was formed in lower proportion. The rate of conjugation of (natural) silybin diastereomers 10S, 11S and 10R, 11R, and therefore also their metabolism in humans is rather different. The radical scavenging activity of 2 is considerably lower than that of its aglycone (1); however, the activity of 3 is higher than in the silybin. These findings corroborate the hypothesis that, at physiological pH, the exclusive target for one-electron oxidation of the silybin molecule is theo-methoxy-phenolic structure at C-19, C-20. This is first pharmacological study using optically pure silybin. The American Society for Pharmacology and Experimental Therapeutics