Abstract
An-Gong-Niu-Huang Wan (AGNHW), a famous formula in traditional Chinese medicine, has been clinically used for centuries for treating cerebral diseases, but the protective effects of pre-treatment with AGNHW on cerebral ischemia have not yet been reported. The present study aimed to test such protective effects and elucidate the underlying mechanisms on cerebral ischemia in rats by phenotypic approaches (i.e. including the neurological functional score, cerebral infarct area, neuron apoptosis, and brain oxidative stress status) and target-based approaches (i.e. involving the GSK-3β/HO-1 pathway). AGNHW was administered orally at the doses of 386.26, 772.52, and 1545.04 mg/kg respectively for 7 days to male Sprague-Dawley rats and then cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 1.5 h. Pre-treatment with AGNHW significantly ameliorated ischemic damage to the brain in a dose-dependent manner, including reduction of the neurological deficit score and infarct area. AGNHW pre-treatment increased the number of Nissl+ cells, NeuN+ and DCX+ cells, and decreased the number of Tunel+ cells. Moreover, AGNHW reversed the up-regulation of ROS and MDA induced by cerebral ischemia. AGNHW pre-treatment increased the expression of p-GSK-3β(Ser9)/GSK-3β (glycogen synthase kinase-3β) ratio and heme oxygenase-1 (HO-1). These results firstly revealed that short-term pre-treatment of AGNHW could significantly protect the rats from injury caused by cerebral ischemia-reperfusion, which support further clinical studies for disease prevention. The in vivo protective effect of AGNWH pre-treatment could be associated with its antioxidant properties by the activation of GSK-3β-mediated HO-1 pathway.
Highlights
Ischemic stroke remains a leading cause of mortality and disability worldwide, with a huge economic burden on the society
The protective effect of An-Gong-Niu-Huang Wan (AGNHW) pre-treatment was monitored by amelioration of neurological deficits and reduction of infarct area
Compared with the middle cerebral artery occlusion (MCAO) group, the neurological scores were markedly reduced in the AGNHW groups in a dose-dependent manner
Summary
Ischemic stroke remains a leading cause of mortality and disability worldwide, with a huge economic burden on the society. Ischemic stroke shows a complex pathophysiological course leading to peroxidation stress, loss of membrane potential, cell depolarization and, eventually, neuronal cell death, involving a variety of distinct molecular and cellular mechanisms of ischemic brain damage (Wan et al, 2020). The pharmaceutical industry has been making huge strides in recent years, the lack of effective anti-stroke drugs remains one of the most unmet needs in medicine (Abe et al, 2019). Stroke is a medical emergency but medications for poststroke treatment are extremely limited in number. A stroke usually causes lasting brain damage, long-term disability, or even death. Prevention is a more effective strategy than cure in the treatment of stroke
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