Stereoselective metabolism of silybin diastereoisomers in the glucuronidation process

• Published in: Journal of pharmaceutical and biomedical analysis Vol. 34; no. 5; pp. 1071 - 1078
• Main Authors: Han, Y.H., Lou, H.X., Ren, D.M., Sun, L.R., Ma, B., Ji, M.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 10.03.2004; Elsevier Science
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Biological and medical sciences; Fundamental and applied biological sciences. Psychology; General pharmacology; Glucuronidation; Glucuronides - chemistry; Glucuronides - metabolism; Medical sciences; Pharmacology. Drug treatments; Plant Extracts - chemistry; Plant Extracts - metabolism; Seeds; Silybin; Silymarin - chemistry; Silymarin - metabolism; Stereoisomerism; Stereoselective metabolism; UV, HPLC/MS, NMR spectrometry; Silybin; Stereoselective metabolism; Glucuronidation; UV, HPLC/MS, NMR spectrometry; Drug; Stereoselective metabolism; Silybin; UV; HPLC/MS; Digestive system; Hepatoprotector; Metabolite; Liver; HPLC chromatography; Ox; Glucuronic acid conjugation; NMR spectrometry; Microsome; Metabolism; Flavonoid; Stereoselectivity; Polyphenol; Vertebrata; Mammalia; Silibinin; Artiodactyla; Ungulata; NMR spectrometry; Glucuronidation
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2003.12.002

A separation method for the hepatoprotective drug silybin and its metabolites by RP-HPLC was described. Based on this separation, the stereoselectivity of the metabolism of silybin was investigated by incubation of the drug and its two diastereoisomers with bovine liver microsomes. Information about the structures of these metabolites was obtained, using UV, HPLC/MS and NMR spectra. Four major metabolites (M1, M4 of silybin A and M2, M5 of silybin B), were prepared by preparative HPLC, and their configurations were accomplished by NMR spectra. A HPLC method was used to quantify the metabolites. The results showed that silybin was extensively metabolized and the major sites for glucuronidation were the C-20, C-7, at phenolic OH groups. Furthermore, the results obtained reveal that there was significant stereoselectivity in the glucuronidation process of silybin. Silybin B was glucuronidated at a more efficient rate than its diastereoisomer, and glucuronidation of silybin B was much preferred at the 20 position, while that of silybin A was similar at both 7 and 20 position.