Flavonolignan 2,3-dehydroderivatives: Preparation, antiradical and cytoprotective activity.

Abstract

The protective constituents of silymarin, an extract from Silybum marianum fruits, have been extensively studied in terms of their antioxidant and hepatoprotective activities. Here, we explore the electron-donor properties of the major silymarin flavonolignans. Silybin (SB), silychristin (SCH), silydianin (SD) and their respective 2,3-dehydroderivatives (DHSB, DHSCH and DHSD) were oxidized electrochemically and their antiradical/antioxidant properties were investigated. Namely, Folin-Ciocalteau reduction, DPPH and ABTS(+) radical scavenging, inhibition of microsomal lipid peroxidation and cytoprotective effects against tert-butyl hydroperoxide-induced damage to a human hepatocellular carcinoma HepG2 cell line were evaluated. Due to the presence of the highly reactive C3-OH group and the C-2,3 double bond (ring C) allowing electron delocalization across the whole structure in the 2,3-dehydroderivatives, these compounds are much more easily oxidized than the corresponding flavonolignans SB, SCH and SD. This finding was unequivocally confirmed not only by experimental approaches, but also by density functional theory (DFT) calculations. The hierarchy in terms of ability to undergo electrochemical oxidation (DHSCH~DHSD>DHSB>>SCH/SD>SB) was consistent with their antiradical activities, mainly DPPH scavenging, as well as in vitro cytoprotection of HepG2 cells. The results are discussed in the context of the antioxidant vs. prooxidant activities of flavonolignans and molecular interactions in complex biological systems.

• Authors: Michaela Pyszková, Michal Biler, David Biedermann, Kateřina Valentová, Marek Kuzma, Jiří Vrba, Jitka Ulrichová, Romana Sokolová, Miloš Mojović, Ana Popović-Bijelić, Martin Kubala, Patrick Trouillas, Vladimír Křen, Jan Vacek
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 90 Pg. 114-25 (Jan 2016) ISSN: 1873-4596 [Electronic] United States
• PMID: 26582372 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Antioxidants
• Flavonolignans
• Silymarin
• Silybin
• silidianin
• silychristin

Topics

• Animals
• Antioxidants (pharmacology)
• Cytoprotection
• Electron Spin Resonance Spectroscopy
• Flavonolignans (chemistry, pharmacology)
• Hep G2 Cells
• Humans
• Male
• Rats
• Silybin
• Silymarin (pharmacology)
• Structure-Activity Relationship