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

Abstract

Infarction 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 microg/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-kappaB) that in turn signaled up-regulation of inflammatory proteins. NF-kappaB 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 anti-oxidative effect, which in turn modulates NF-kappaB activation that mediates CI/R injury.

• Authors: Yea-Hwey Wang, Wen-Yen Wang, Chia-Che Chang, Kuo-Tong Liou, Yen-Jen Sung, Jyh-Fei Liao, Chieh-Fu Chen, Shiou Chang, Yu-Chang Hou, Yueh-Ching Chou, Yuh-Chiang Shen
• Journal: Journal of biomedical science (J Biomed Sci) Vol. 13 Issue 1 Pg. 127-41 (Jan 2006) ISSN: 1021-7770 [Print] England
• PMID: 16283433 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Antioxidants
• Flavonols
• Macrophage-1 Antigen
• NF-kappa B
• Reactive Oxygen Species
• Intercellular Adhesion Molecule-1
• Nitric Oxide
• Quercetin
• taxifolin
• Nitric Oxide Synthase Type II
• Cyclooxygenase 2

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (chemistry, metabolism, therapeutic use)
• Antioxidants (therapeutic use)
• Brain Ischemia (drug therapy, pathology)
• Cerebral Cortex (metabolism)
• Cyclooxygenase 2 (metabolism)
• Flavonols (chemistry, metabolism, therapeutic use)
• Intercellular Adhesion Molecule-1 (metabolism)
• Leukocytes (metabolism)
• Macrophage-1 Antigen (metabolism)
• Male
• Microglia (metabolism)
• Molecular Structure
• NF-kappa B (metabolism)
• Neutrophils (metabolism)
• Nitric Oxide (metabolism)
• Nitric Oxide Synthase Type II (metabolism)
• Quercetin (analogs & derivatives, chemistry, metabolism, therapeutic use)
• Rats
• Rats, Long-Evans
• Reactive Oxygen Species (metabolism)
• Reperfusion Injury (drug therapy, pathology)