Ferulic acid regulates the AKT/GSK-3beta/CRMP-2 signaling pathway in a middle cerebral artery occlusion animal model.
- Author:
Sang A GIM
1
;
Jin Hee SUNG
;
Fawad Ali SHAH
;
Myeong Ok KIM
;
Phil Ok KOH
Author Information
- Publication Type:Original Article
- Keywords: Ferulic acid; neuroprotection; Akt; GSK-3beta; CRMP-2
- MeSH: Angelica sinensis; Animals; Brain Injuries; Brain Ischemia; Cerebral Cortex; Coumaric Acids; Glycogen Synthase; Glycogen Synthase Kinase 3; Humans; Infarction, Middle Cerebral Artery; Ligusticum; Male; Middle Cerebral Artery; Neuroprotective Agents; Phosphorylation; Proteins; Rats; Semaphorin-3A
- From:Laboratory Animal Research 2013;29(2):63-69
- CountryRepublic of Korea
- Language:English
- Abstract: Ferulic acid, a component of the plants Angelica sinensis (Oliv.) Diels and Ligusticum chuanxiong Hort, exerts a neuroprotective effect by regulating various signaling pathways. This study showed that ferulic acid treatment prevents the injury-induced increase of collapsin response mediator protein 2 (CRMP-2) in focal cerebral ischemia. Glycogen synthase kinase-3beta (GSK-3beta) regulates CRMP-2 function through phosphorylation of CRMP-2. Moreover, the pro-apoptotic activity of GSK-3beta is inactivated by phosphorylation by Akt. This study investigated whether ferulic acid modulates the expression of CRMP-2 and its upstream targets, Akt and GSK-3beta, in focal cerebral ischemia. Male rats were treated immediately with ferulic acid (100 mg/kg, i.v.) or vehicle after middle cerebral artery occlusion (MCAO), and then cerebral cortices were collected 24 hr after MCAO. MCAO resulted in decreased levels of phospho-Akt and phospho-GSK-3beta, while ferulic acid treatment prevented the decrease in the levels of these proteins. Moreover, phospho-CRMP-2 and CRMP-2 levels increased during MCAO, whereas ferulic acid attenuated these injury-induced increases. These results demonstrate that ferulic acid regulates the Akt/GSK-3beta/CRMP-2 signaling pathway in focal cerebral ischemic injury, thereby protecting against brain injury.
