Taxifolin ameliorates cerebral ischemia-reperfusion injury in rats through its anti-oxidative effect and modulation of NF-kappa B activation

Abstract

SummaryInfarction in adult rat brain was induced by middle cerebral arterial occlusion (MCAO) followed by reperfusion to examine whether taxifolin could reduce cerebral ischemic reperfusion (CI/R) injury. Taxifolin administration (0.1 and 1.0 lg/kg, i.v.) 60 min after MCAO ameliorated infarction (by 42%±7% and 62%±6%, respectively), which was accompanied by a dramatic reduction in malondialdehyde and nitrotyrosine adduct formation, two markers for oxidative tissue damage. Overproduction of reactive oxygen species (ROS) and nitric oxide (NO) via oxidative enzymes (e.g., COX-2 and iNOS) was responsible for this oxidative damage. Taxifolin inhibited leukocyte infiltration, and COX-2 and iNOS expressions in CI/R-injured brain. Taxifolin also prevented Mac-1 and ICAM-1 expression, two key counter-receptors involved in firm adhesion/transmigration of leukocytes to the endothelium, which partially accounted for the limited leukocyte infiltration. ROS, generated by leukocytes and microglial cells, activated nuclear factor-kappa B (NF-jB) that in turn signaled up-regulation of inflammatory proteins. NF-jB activity in CI/R was enhanced 2.5-fold over that of sham group and was inhibited by taxifolin. Production of both ROS and NO by leukocytes and microglial cells was significantly antagonized by taxifolin. These data suggest that amelioration of CI/R injury by taxifolin may be attributed to its antioxidative effect, which in turn modulates NF-jB activation that mediates CI/R injury.

Flavanonol Taxifolin Attenuates Proteasome Inhibition-Induced Apoptosis in Differentiated PC12 Cells by Suppressing Cell Death Process

“…In contrast to this report, taxifolin has been shown to do not prevent H 2 O 2 -induced cell death in PC12 cells [19]. Taxifolin inhibits cerebral ischaemia-reperfusion injury in rats through suppression of leukocyte infiltration and by inhibition of cyclooxygenase-2 and the expression of inducible nitric oxide synthase [20]. Taxifolin glycoside reduces the microbial component-or IL-1b-induced production of cytokines and formation of reactive oxygen species and nitric oxide in dendritic cells of bone marrow and spleen [21].…”

Taxifolin Inhibits Receptor Activator of NF-κB Ligand-Induced Osteoclastogenesis of Human Bone Marrow-Derived Macrophages in vitro and Prevents Lipopolysaccharide-Induced Bone Loss in vivo

“…The induction of NFATc1 upregulates the osteoclast-specific genes expression, such as TRAP, MMP-9, and CTK. Previous studies have shown, taxifolin exerted its biological effect via modulating NF-κB signaling [22,31]. In the present research, we observed that the taxifolin treatment inhibits the RANKL-induced NF-κB pathway activation, which was accomplished by the suppression of IκBα and NF-κB p65 phosphorylation.…”

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.…”