Chlorogenic acid ameliorates brain damage and edema by inhibiting matrix metalloproteinase-2 and 9 in a rat model of focal cerebral ischemia.
Chlorogenic acid (CGA) has been reported to have various beneficial effects on the cardiovascular and central nervous systems. The purpose of the current study was to investigate whether CGA has protective effects against cerebral ischemia and whether these effects are due to modification of brain edema-related vascular factors. In a rat model of transient middle cerebral artery occlusion (MCAo, 2h of occlusion followed by 22 h of reperfusion), we measured infarct volume and performed behavioral test to evaluate the effects of CGA on brain damage and sensory-motor functional deficits. Brain water content and Evans blue extravasation were measured to evaluate brain edema and blood brain barrier (BBB) damage. Lipid peroxidation (LPO) and the expressions and activities of matrix metalloproteinase (MMP)-2 and MMP-9 were measured to investigate the mechanisms of action. Intraperitoneal injection of CGA (3, 10, and 30 mg/kg) at 0 h and 2h after MCAo dose-dependently reduced infarct volume and sensory-motor functional deficits. It also reduced brain water content and Evans blue extravasation. Mechanistically, CGA reduced LPO and MMPs expressions and activities. These results suggest that CGA reduces brain damage, BBB damage and brain edema by radical scavenging activity and the inhibitory effects on MMP-2 and MMP-9.
College of Oriental Medicine, Kyung Hee University, Seoul 130 701, Republic of Korea.
Kyungjin
K
Lee
Jeong-Sook
JS
Lee
Hyeung-Jin
HJ
Jang
Sung-Moo
SM
Kim
Mun Seog
MS
Chang
Si Hyung
SH
Park
Kwan Su
KS
Kim
Jinhyun
J
Bae
Jae-Woo
JW
Park
Bumjun
B
Lee
Ho-Young
HY
Choi
Chang-Hyun
CH
Jeong
Youngmin
Y
Bu
D000818:Animals; D001929:Brain Edema / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002726:Chlorogenic Acid / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley
D061965:Matrix Metalloproteinase Inhibitors; D018696:Neuroprotective Agents; D002726:Chlorogenic Acid; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9