Theaflavin ameliorates cerebral ischemia-reperfusion injury in rats through its anti-inflammatory effect and modulation of STAT-1.
Theaflavin, a major constituent of black tea, possesses biological functions such as the antioxidative, antiviral, and anti-inflammatory ones. The purpose of this study was to verify whether theaflavin reduces focal cerebral ischemia injury in a rat model of middle cerebral artery occlusion (MCAO). Male Sprague-Dawley rats were anesthetized and subjected to 2 hours of MCAO followed 24 hours reperfusion. Theaflavin administration (5, 10, and 20 mg/kg, i.v.) ameliorated infarct and edema volume. Theaflavin inhibited leukocyte infiltration and expression of ICAM-1, COX-2, and iNOS in injured brain. Phosphorylation of STAT-1, a protein which mediates intracellular signaling to the nucleus, was enhanced 2-fold over that of sham group and was inhibited by theaflavin. Our study demonstrated that theaflavin significantly protected neurons from cerebral ischemia-reperfusion injury by limiting leukocyte infiltration and expression of ICAM-1, and suppressing upregulation of inflammatory-related prooxidative enzymes (iNOS and COX-2) in ischemic brain via, at least in part, reducing the phosphorylation of STAT-1.
Cai
Fei
F
Department of Pharmacology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Li
Cai-Rong
CR
Wu
Ji-Liang
JL
Chen
Jian-Guo
JG
Liu
Chao
C
Min
Qing
Q
Yu
Wei
W
Ouyang
Chang-Han
CH
Chen
Jin-He
JH
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D044946:Biflavonoids / Q000494:pharmacology*; D001929:Brain Edema / Q000188:drug therapy / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism*; D002392:Catechin / Q000494:pharmacology*; D002544:Cerebral Infarction / Q000188:drug therapy / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000235:genetics; D018836:Inflammation Mediators / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis / Q000235:genetics; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D050794:STAT1 Transcription Factor / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D044946:Biflavonoids; D018836:Inflammation Mediators; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494081:Stat1 protein, rat; D018799:Intercellular Adhesion Molecule-1; C056068:theaflavin; D008315:Malondialdehyde; D002392:Catechin; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat