This study was designed to investigate the effect of 002C-3, a derivative of magnolol, on transient cerebral middle occlusion （tMCAO） in a mice model and to identify the underlying mechanisms. 002C-3 （100 and 150 p...This study was designed to investigate the effect of 002C-3, a derivative of magnolol, on transient cerebral middle occlusion （tMCAO） in a mice model and to identify the underlying mechanisms. 002C-3 （100 and 150 pg/kg, i.v. after ending occlusion） significantly reduced neurological deficit scores, infarct volumes, and brain water contents after 1.5 h MCAO and 24 h reperfusion. 002C-3 （75 150μg/kg） decreased the exudation of Evans blue from brain capillaries. 002C-3 （100 μg/kg） significantly inhibited the activity of MMP-9 and MMP-2 in the injured hemisphere. 002C-3 decreased the expression of autophagy-associated proteins, Beclin-1 and LC3B-Ⅱ, and increased the level of p62 in injured hemisphere. 002C-3 （100 pg/kg） significantly increased the expression of p-CaMKIV and p-HDAC4 in injured hemisphere. In conclusion, 002C-3 shows a neuroprotective effect on tMCAO injury in mice, and its mechanisms may be associated with alleviation of blood-brain barrier damage caused by the activation of MMPs, inhibition of autophagy, and stimulation of calcium signals related to cell survival. These findings suggest that 002C-3 is a neuroprotective agent that acts on multiple pathways.展开更多
基金National Natural Science Foundation of China(Grant No.81302763,81573333)Beijing Natural Science Foundation(Grant No.7144218)
文摘This study was designed to investigate the effect of 002C-3, a derivative of magnolol, on transient cerebral middle occlusion （tMCAO） in a mice model and to identify the underlying mechanisms. 002C-3 （100 and 150 pg/kg, i.v. after ending occlusion） significantly reduced neurological deficit scores, infarct volumes, and brain water contents after 1.5 h MCAO and 24 h reperfusion. 002C-3 （75 150μg/kg） decreased the exudation of Evans blue from brain capillaries. 002C-3 （100 μg/kg） significantly inhibited the activity of MMP-9 and MMP-2 in the injured hemisphere. 002C-3 decreased the expression of autophagy-associated proteins, Beclin-1 and LC3B-Ⅱ, and increased the level of p62 in injured hemisphere. 002C-3 （100 pg/kg） significantly increased the expression of p-CaMKIV and p-HDAC4 in injured hemisphere. In conclusion, 002C-3 shows a neuroprotective effect on tMCAO injury in mice, and its mechanisms may be associated with alleviation of blood-brain barrier damage caused by the activation of MMPs, inhibition of autophagy, and stimulation of calcium signals related to cell survival. These findings suggest that 002C-3 is a neuroprotective agent that acts on multiple pathways.
