As shown in Fig. 1 (right panel), the condensation between taxifolin and coniferyl alcohol has two possible outcomes, thereby
generating two different molecules that differ based on the position of the primary alcohol, which can either extend out of the page, or face into the page. Thus, silybin B has the alcohol protruding from the page and the benzene ring faces into the page, while silybin A has the opposite configuration. Since there are two different stereocenters that differ between silybin A and silybin B, they are called diastereoisomers. Since there is inconsistency in the literature with respect to naming silymarin-derived compounds, we adopt the recommendations of Kroll et al.19: Silymarin is the entire extract containing seven flavonolignans and taxifolin. Silibinin is a mixture of silybin A and silybin B in a 1:1 ratio. The remaining flavonolignans GSK3235025 molecular weight are: isosilybin A, isosilybin B, silychristin, isosilychristin, and silydianin. The flavonoid found in silymarin is taxifolin. The structures of the eight compounds are shown in Fig. 2. In a typical preparation of silymarin, the approximate percentages of the eight major components DZNeP ic50 are silybin A (16%), silybin B (24%), isosilybin A (6%), isosilybin B (4%), silydianin (16%), silychristin (12%), isosilychristin
(2%), and taxifolin (2%).20 The product composition totals are less than 100% because a typical extract is usually labeled as 70% to 80% silymarin, with the remainder consisting of uncharacterized medchemexpress polyphenols and aliphatic fatty acids such
as oleic and palmitic acids. Silymarin is fat soluble, with an oral bioavailability of 30%-50%. In healthy subjects, oral dosing of silymarin results in low plasma concentrations of flavonolignans between 50-300 ng/mL because the parent compounds are rapidly metabolized to glucuronide and sulfate conjugates which are not thought to have biological activity.21-25 Plasma levels typically achieve maximum concentration after ∼1-2 hours, with an estimated half-life of 4-6 hours.21, 24, 25 Approximately 20%-40% is conjugated and excreted in the bile, 3%-8% excreted in the urine, and the remainder excreted unabsorbed in the feces.26 In cirrhosis patients, the peak serum concentration and time to peak concentration are delayed, suggesting that impaired biliary excretion may be associated with reduced clearance of conjugated silibinin.26 This has also been observed for cirrhosis patients with chronic HCV, who have 3- to 5-fold higher plasma concentrations of flavonolignan conjugates as compared to healthy subjects.6, 27, 28 Silymarin may induce cytochrome P450, isoform 3A429 and p-glycoprotein,30 which may alter the pharmacokinetics of oral contraceptive pills. Metabolism of other drugs may also be affected, including antihistamines, benzodiazepines, protease-inhibitors, and cholesterol-lowering agents.