This review focuses on the specific biological effects of optically pure silymarin flavo-nolignans, mainly silybins A and B, isosilybins A and B, silychristins A and B, and their 2,3-dehydro derivatives. The chirality of these flavonolignans is also discussed in terms of their analysis, preparative separation and chemical reactions. We demonstrated the specific activities of the respective diastereomers of flavonolignans and also the enantiomers of their 2,3-dehydro derivatives in the 3D anisotropic systems typically represented by biological systems. In vivo, silymarin flavonolignans do not act as redox antioxidants, but they play a role as specific ligands of biological targets, according to the "lock-and-key" concept. Estrogenic, antidiabetic, anticancer, antiviral, and antiparasitic effects have been demonstrated in optically pure flavonolignans. Potential application of pure flavonolignans has also been shown in cardiovascular and neurological diseases. Inhibition of drug-metabolizing enzymes and modulation of multidrug resistance activity by these compounds are discussed in detail. The future of "silymarin applications" lies in the use of optically pure components that can be applied directly or used as valuable lead structures, and in the exploration of their true molecular effects.

• Klíčová slova
• Silybum marianum, chirality, dehydroflavonolignan, diastereomer, flavonoid, flavonolignan, isosilybin, milk thistle, silibinin, silybin, silychristin, silydianin, silymarin,
• MeSH
• antiinfekční látky chemie   farmakologie   MeSH
• antioxidancia chemie   farmakologie   MeSH
• fytogenní protinádorové látky chemie   farmakologie   MeSH
• lidé MeSH
• silibinin chemie   farmakologie   MeSH
• stereoizomerie MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• antiinfekční látky MeSH
• antioxidancia MeSH
• fytogenní protinádorové látky MeSH
• silibinin MeSH

2,3-Dehydrosilybin A and 2,3-dehydrosilybin B are a pair of enantiomers formed by the oxidation of the natural flavonolignans silybin A and silybin B, respectively. However, the antioxidant activity of 2,3-dehydrosilybin molecules is much stronger than that of their precursors. Here, we investigated the biotransformation of pure 2,3-dehydrosilybin A and 2,3-dehydrosilybin B in isolated human hepatocytes, and we also aimed to identify human UDP-glucuronosyltransferases (UGTs) and sulfotransferases (SULTs) with activity toward their respective enantiomers. After incubation with hepatocytes, both 2,3-dehydrosilybin A and 2,3-dehydrosilybin B were converted to hydroxyl derivatives, methylated hydroxyl derivatives, methyl derivatives, sulfates, and glucuronides. The products of direct conjugations predominated over those of oxidative metabolism, and glucuronides were the most abundant metabolites. Furthermore, we found that recombinant human UGTs 1A1, 1A3, 1A7, 1A8, 1A9, and 1A10 were capable of catalyzing the glucuronidation of both 2,3-dehydrosilybin A and 2,3-dehydrosilybin B. UGTs 1A1 and 1A7 showed the highest activity toward 2,3-dehydrosilybin A, and UGT1A9 showed the highest activity toward 2,3-dehydrosilybin B. The sulfation of 2,3-dehydrosilybin A and B was catalyzed by SULTs 1A1*1, 1A1*2, 1A2, 1A3, 1B1, 1C2, 1C4, and 1E1, of which SULT1A3 exhibited the highest activity toward both enantiomers. We conclude that 2,3-dehydrosilybin A and B are preferentially metabolized by conjugation reactions, and that several human UGT and SULT enzymes may play a role in these conjugations.

• Klíčová slova
• UDP-glucuronosyltransferase, dehydrosilybin, glucuronidation, metabolism, silybin, sulfation, sulfotransferase,
• Publikační typ
• časopisecké články MeSH

Numerous chronic diseases including cancer, cardiovascular, chronic respiratory or neurodegenerative diseases, diabetes mellitus, retinal damage, and others are associated with oxidative stress [...].

• Publikační typ
• úvodníky MeSH