Green tea polyphenol (-)-epigallocatechin gallate reduces matrix metalloproteinase-9 activity following transient focal cerebral ischemia.
Green tea polyphenol (-)-epigallocatechin gallate (EGCG) has been reported to reduce neuronal damage after cerebral ischemic insult. EGCG is known to reduce matrix metalloproteinase (MMP) activity. MMP can play an important role in the pathophysiology of neurological disorders including cerebral ischemia. The purpose of the current study was to investigate whether EGCG shows an inhibitory effect on MMP activity and neural tissue damage following transient focal cerebral ischemia. In the present study, C57BL/6 mice were subjected to 80 min of focal ischemia induced by middle cerebral artery occlusion (MCAO). Animals were killed 24 h after ischemia. EGCG (50 mg/kg) was administered intraperitoneally immediately after ischemia. Gelatin gel zymography showed an increase in the active form of MMP-9 after ischemia. EGCG reduced ischemia-induced up-regulation of the active form of MMP-9. In in situ zymography, EGCG reduced up-regulation of gelatinase activity induced by cerebral ischemia. Co-incubation with EGCG reduced gelatinase activity directly in postischemic brain section. In 2,3,5-triphenyltetrazolium chloride (TTC) assay, brain infarction was remarkable in the middle cerebral artery territory after focal cerebral ischemia. In EGCG-treated mice, infarct volume was significantly reduced compared with vehicle-treated mice. These results demonstrate that EGCG, a green tea polyphenol, may reduce up-regulation of MMP-9 activity and neuronal damage following transient focal cerebral ischemia. In addition to its antioxidant effect, MMP-9 inhibition might be a possible mechanism potentially involved in the neuroprotective effect of a green tea polyphenol, EGCG.
Park
Jong-Wook
JW
Chronic Disease Research Center and Institute for Medical Science, School of Medicine, Keimyung University, Taegu 700-712, South Korea. j303nih@dsmc.or.kr
Hong
Jung-Seok
JS
Lee
Kyoung-Suk
KS
Kim
Hahn-Young
HY
Lee
Jung-Jeung
JJ
Lee
Seong-Ryong
SR
D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005419:Flavonoids / Q000627:therapeutic use; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010636:Phenols / Q000627:therapeutic use; D059808:Polyphenols; D013662:Tea / Q000737:chemistry*; D013778:Tetrazolium Salts / Q000378:metabolism; D015854:Up-Regulation
D005419:Flavonoids; D061965:Matrix Metalloproteinase Inhibitors; D018696:Neuroprotective Agents; D010636:Phenols; D059808:Polyphenols; D013662:Tea; D013778:Tetrazolium Salts; C009591:triphenyltetrazolium; D002392:Catechin; C045651:epigallocatechin gallate; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse