Dihydroquercetin (taxifolin) and other flavonoids as inhibitors of free radical formation at key stages of apoptosis

Abstract

Formation of free radicals in mitochondria plays a key role in the development of apoptosis, which includes formation of superoxide by the respiratory chain, formation of radicals by cytochrome c-cardiolipin complex in the presence of hydrogen peroxide or lipids, and chain lipid peroxidation resulting in cytochrome c release from mitochondria and initiation of the apoptotic cascade. In this work the effect of taxifolin (dihydroquercetin) and some other antioxidants on these three radical-producing reactions was studied. Peroxidase activity of the complex of cytochrome c with dioleyl cardiolipin estimated by chemiluminescence with luminol decreased by 50% with quercetin, taxifolin, rutin, Trolox, and ionol at concentrations 0.7, 0.7, 0.8, 3, and 10 microM, respectively. The lipid radical production detected by coumarin C-525-activated chemiluminescence decreased under the action of rutin and taxifolin in a dose-dependent manner, so that a 50% inhibition of chemiluminescence was observed at the antioxidant concentrations of 3.7 and 10 microM, respectively. Thus, these two radical-producing reactions responsible for apoptosis onset are inhibited by antioxidants at rather low concentrations. Experiments performed on liver slices and mash showed that taxifolin, quercetin, naringenin, and Trolox have low inhibitory effect on the lucigenin-dependent chemiluminescence in the tissue only at concentrations higher than 100 microM.

Acetylcholinesterase and carbonic anhydrase isoenzymes I and II inhibition profiles of taxifolin

“…Researchers have demonstrated that taxifolin decreased the production of lipid radicals in a concentration-dependent manner and reduced the peroxidase activity of the complex of cytochrome c combined with dioleoyl cardiolipin, which is critical for the onset of apoptosis. Taxifolin also ameliorated cerebral ischemiareperfusion injury by inhibiting oxidative enzymes and reducing the overproduction of ROS 27,28 . Taxifolin inhibited recombinant human aldose reductase and the accumulation of sorbitol in human erythrocyte in diabetes.…”

Adsorption of Monovalent Ions to Phosphatidylcholine-Cardiolipin Membranes

“…Cardiolipin (diphosphatidylglycerol, CL) is an anionic phospholipid component of the cell membrane in many types of bacteria and in eukaryotic mitochondrial membranes (8,9). The structure consists of a glycerol-based phospholipid containing four acyl chains and three hydrophilic groups (10).…”

In vitro cultures of carnivorous plants from the Drosera and Dionaea genus for the production of biologically active secondary metabolites

“…Their basic function is to protect the cells from oxidative stress due to their strong antioxidant properties and ability to scavenge free radicals (Lin et al, 2002;Vladimirov et al, 2009). The most interesting function of this group of compounds is their antimicrobial properties.…”