Protective Effects of AGNHW Pre-treatment on Cerebral Ischemia

Pre-treatment with AGNHW significantly ameliorated, in a dose-dependent manner, ischemic damage to the brain, as reflected in a reduction of the neurological deficit score and a decrease in the infarct area. These results firstly established that short-term pre-treatment with AGNHW could significantly protect rats from injury caused by cerebral ischemia-reperfusion. Hence further clinical studies on the use of AGNWH for the prevention of neurological diseases are warranted. The in vivo protective effect of AGNWH pre-treatment could be associated with its antioxidant property manifested through activation of the glycogen synthase kinase- 3β(GSK-3β)-mediated heme oxygenase-1(HO-1) pathway. in the present study, administration of the human equivalent dose of AGNHW (low-dose group, 386.26 mg/kg/day) produced a pronounced protective effect on the rat model of MCAO. Mechanistic studies disclosed that pre-treatment with AGNHW could upregulate an inhibitory phosphorylation of GSK-3β at the Ser 9 residue without affecting the protein expression level of total GSK-3β and subsequently promote the protein expression of its downstream target HO-1. A number of studies have indicated that inhibition of GSK-3β ameliorated cerebral ischemia injury. Therefore, the effect of AGNHW pre-treatment is probably attributed to its protective action on neurons against oxidative stress damage, which is produced via activation of the GSK-3β-mediated HO-1 pathway. In the present investigation, AGNHW pre-treatment reduced significantly, in a dose￾dependent manner, the levels of reactive oxygen species and malondialdehyde in infarct tissue in the ischemic brain cortex. The findings indicate a protective effect of AGNHW on– damage elicited by oxidative stress. In conclusion, the present report is the first which demonstrates that AGNHW pretreatment of a rat model of ischemic stroke for 7 consecutive days effectively curtailed injury brought about in the ischemic brain by activation of the GSK-3β-mediated HO-1 pathway.