Neuroprotective effect of nobiletin on cerebral ischemia-reperfusion injury in transient middle cerebral artery-occluded rats.

Abstract

Nobiletin, a citrus polymethoxylated flavone, is reported to possess various pharmacological activities such as anticancer, anti-inflammation, and antioxidant effects. Recently, nobiletin was shown to provide therapeutic benefit for the treatment of Alzheimer׳s disease by activating cAMP-response element-binding protein (CREB). In the present study, we investigated whether nobiletin could protect the brain against ischemia-reperfusion (I/R) injury and improve functional outcome in cerebral I/R model rats, since CREB activation is known to protect neuronal cells in cerebral ischemia. Nobiletin was injected twice at 0 and 1h after the start of reperfusion in transient middle cerebral artery occlusion (t-MCAO) rats. Cerebral I/R induced prominent brain damage in the ischemic hemisphere of t-MCAO rat brains; however, nobiletin treatment significantly reduced the infarct volume and suppressed the brain edema. Immunohistochemical and TUNEL staining indicated that nobiletin treatment significantly suppressed neutrophil invasion into the ischemic region and significantly decreased apoptotic brain cell death in ischemic hemisphere, suggesting that the anti-inflammatory effect and anti-apoptotic effect should be regarded as the neuroprotective mechanism of nobiletin. Moreover, nobiletin treatment ameliorated motor functional deficits in the ischemic rats compared with those deficits of the vehicle-treated group. These results indicate that nobiletin is a potential neuroprotectant for the treatment of cerebral I/R injury.

• Authors: Nodoka Yasuda, Takayuki Ishii, Dai Oyama, Tatsuya Fukuta, Yurika Agato, Akihiko Sato, Kosuke Shimizu, Tomohiro Asai, Tomohiro Asakawa, Toshiyuki Kan, Shizuo Yamada, Yasushi Ohizumi, Naoto Oku
• Journal: Brain research (Brain Res) Vol. 1559 Pg. 46-54 (Apr 22 2014) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 24534366 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Flavones
• Neuroprotective Agents
• nobiletin

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacokinetics, pharmacology)
• Apoptosis (drug effects)
• Brain (drug effects, pathology)
• Brain Edema (drug therapy, etiology, pathology)
• Disease Models, Animal
• Flavones (pharmacokinetics, pharmacology)
• Infarction, Middle Cerebral Artery (complications, drug therapy, pathology)
• Ischemic Attack, Transient (complications, drug therapy, pathology)
• Male
• Motor Activity (drug effects)
• Neurons (drug effects, pathology)
• Neuroprotective Agents (pharmacokinetics, pharmacology)
• Neutrophils (drug effects, pathology)
• Rats
• Rats, Wistar
• Reperfusion Injury (complications, drug therapy, pathology)
• Treatment Outcome