PT - JOURNAL ARTICLE AU - Vladimír Kr̆en AU - Jitka Ulrichová AU - Pavel Kosina AU - David Stevenson AU - Petr Sedmera AU - Věra Přikrylová AU - Petr Halada AU - Vilím šsimánek 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