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Chlorogenic acid ameliorates brain damage and edema by inhibiting matrix metalloproteinase-2 and 9 in a rat model of focal cerebral ischemia.

Abstract
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.
AuthorsKyungjin Lee, Jeong-Sook Lee, Hyeung-Jin Jang, Sung-Moo Kim, Mun Seog Chang, Si Hyung Park, Kwan Su Kim, Jinhyun Bae, Jae-Woo Park, Bumjun Lee, Ho-Young Choi, Chang-Hyun Jeong, Youngmin Bu
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 689 Issue 1-3 Pg. 89-95 (Aug 15 2012) ISSN: 1879-0712 [Electronic] Netherlands
PMID22659584 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2012 Elsevier B.V. All rights reserved.
Chemical References
  • Matrix Metalloproteinase Inhibitors
  • Neuroprotective Agents
  • Chlorogenic Acid
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
Topics
  • Animals
  • Brain Edema (drug therapy, enzymology, pathology)
  • Brain Ischemia (drug therapy, enzymology, pathology)
  • Chlorogenic Acid (pharmacology, therapeutic use)
  • Disease Models, Animal
  • Matrix Metalloproteinase 2 (metabolism)
  • Matrix Metalloproteinase 9 (metabolism)
  • Matrix Metalloproteinase Inhibitors (pharmacology, therapeutic use)
  • Neuroprotective Agents (pharmacology, therapeutic use)
  • Rats
  • Rats, Sprague-Dawley

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