The mechanism of (+) taxifolin's protective antioxidant effect for ·OH-treated bone marrow-derived mesenchymal stem cells

Abstract

The natural dihydroflavonol (+) taxifolin was investigated for its protective effect on Fenton reagent-treated bone marrow-derived mesenchymal stem cells (bmMSCs). Various antioxidant assays were used to determine the possible mechanism. These included ·OH-scavenging, 2-phenyl-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide radical-scavenging (PTIO·-scavenging), 1, 1-diphenyl-2-picryl-hydrazl radical-scavenging (DPPH·-scavenging), 2, 2'-azino-bis (3-ethylbenzo-thiazoline-6-sulfonic acid) radical-scavenging (ABTS+·-scavenging), Fe3+-reducing, and Cu2+-reducing assays. The Fe2+-binding reaction was also investigated using UV-Vis spectra. The results revealed that cell viability was fully restored, even increasing to 142.9±9.3% after treatment with (+) taxifolin. In the antioxidant assays, (+) taxifolin was observed to efficiently scavenge ·OH, DPPH· and ABTS+· radicals, and to increase the relative Cu2+- and Fe3+-reducing levels. In the PTIO·-scavenging assay, its IC50 values varied with pH. In the Fe2+-binding reaction, (+) taxifolin was found to yield a green solution with two UV-Vis absorbance peaks: λmax =433 nm (ε =5.2×102 L mol-1 cm -1) and λmax =721 nm (ε=5.1×102 L mol-1 cm -1). These results indicate that (+) taxifolin can act as an effective ·OH-scavenger, protecting bmMSCs from ·OH-induced damage. Its ·OH-scavenging action consists of direct and indirect antioxidant effects. Direct antioxidation occurs via multiple pathways, including ET, PCET or HAT. Indirect antioxidation involves binding to Fe2+.