Taxifolin ameliorates cerebral ischemia-reperfusion injury in rats through
its anti-oxidative effect and modulation of NF-kappa B activation |
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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 |
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Institution: | (1) Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan;(2) Departments of Surgery and Chinese Medicine, Tao-yuan and Hsin-chu General Hospitals, Department of Health, Taipei, Taiwan;(3) National Research Institute of Chinese Medicine, Taipei, Taiwan;(4) Anatomy and Cell Biology, School of Medicine, National Yang-Ming University, Taipei, Taiwan;(5) Institute of Biomedical Sciences, National Chung-Hsing University, Taichung, Taiwan;(6) Department of Chinese Martial Arts, Chinese Culture University, Taipei, Taiwan;(7) Department of Pharmacy, Veterans General Hospital, Taipei, Taiwan;(8) School of Pharmacy, Taipei Medical University, Taipei, Taiwan |
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Abstract: | Summary 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 μg/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-κB) that in turn signaled
up-regulation of inflammatory proteins. NF-κB 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-κB activation that mediates CI/R injury.
Yea-Hwey Wang, Wen-Yen Wang, Chia-Che Chang, and Kuo-Tong Liou contributed equally to this work. |
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Keywords: | cerebral ischemic-reperfusion COX-2 ICAM-1 (CD54) iNOS Mac-1 (CD11b/CD18) nuclear factor kappa B (NF-κ B) reactive oxygen species taxifolin |
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