PT  - JOURNAL ARTICLE
AU  - Kr̆en, Vladimír
AU  - Ulrichová, Jitka
AU  - Kosina, Pavel
AU  - Stevenson, David
AU  - Sedmera, Petr
AU  - Přikrylová, Věra
AU  - Halada, Petr
AU  - šsimánek, Vilím
TI  - Chemoenzymatic Preparation of Silybin β-Glucuronides and Their Biological Evaluation
DP  - 2000 Dec 01
TA  - Drug Metabolism and Disposition
PG  - 1513--1517
VI  - 28
IP  - 12
4099  - http://dmd.aspetjournals.org/content/28/12/1513.short
4100  - http://dmd.aspetjournals.org/content/28/12/1513.full
SO  - Drug Metab Dispos2000 Dec 01; 28
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