Magnolol derivative 002C-3 protects brain against ischemia-reperfusion injury via inhibiting apoptosis and autophagy

Neuroprotective agents can rescue ischemic penumbra in cerebral ischemia. However, the clinically effective neuroprotective agents for cerebral ischemic injury remain deficient in clinic so far. This study was undertaken to investigate the brain protective effect of 002C-3 and its potential mechanisms in rats, and its preliminary toxicity in mice. A transient middle cerebral artery occlusion (tMCAO) model in rats was used to evaluate its effect and mechanism, a dose limited experiment was used to evaluate its preliminary toxicity. 10-50 mu g/kg of 002C-3 (single iv bolus after reperfusion) significantly reduced neurological scores, infarct volumes and brain water contents, and the effect was more potent than that of magnolol under the same mole dose; 50 mu g/kg of 002C-3 significantly decreased the number of TUNEL-positive cells, reduced the activity of caspase-3, and lowered the autophagy-related proteins LC3-II and Beclin-1 level in cerebral tissue. At 1000 times dose of high effective dose (ip) 002C-3 failed to show evident toxicity in mice, and the mean body weight of mice treated with 002C-3 was almost the same as that of the vehicle control, but magnolol caused evident toxicity and death. In conclusion, 002C-3 has significant protective effect against cerebral ischemia-reperfusion injury; the effect is more potent than magnolol; this effect is maybe associated with its inhibition of both apoptosis and autophagy; its toxicity is greatly reduced compared to magnolol. These results provided data for its further research and development. (C) 2015 Elsevier Ireland Ltd. All rights reserved.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000350922300032&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701NeurosciencesSCI(E)PubMed3ARTICLEwangyinye@bjmu.edu.cn178-18358