- 作者: 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
- 作者服務機構: 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
- 中文摘要: --
- 英文摘要: 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 malondial-dehyde 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-I and ICAM-I 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-κΒ) that in turn signaled up-regulation of inflammatory proteins. NF-κΒ 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.
- 中文關鍵字: --
- 英文關鍵字: cerebral ischemic-reperfusion, COX-2, ICAM-1 (CD54), iNOS, Mac-1 (CD11b/CD18), nuclear factor kappa B (NF-κΒ), reactive oxygen species, taxifolin