TY - JOUR
T1 - Protective Effect of An-Gong-Niu-Huang Wan Pre-treatment Against Experimental Cerebral Ischemia Injury via Regulating GSK-3β/HO-1 Pathway
AU - Zhang, Shiqing
AU - Jiang, Xiaoli
AU - Wang, Ying
AU - Lin, Kaili
AU - Zhang, Zhang
AU - Zhang, Zhu
AU - Zhu, Peili
AU - Ng, Man Ling
AU - Qu, Shaogang
AU - Sze, Cho Wing
AU - Yung, Kin Lam
N1 - Funding Information:
This study was financially supported by the following grants: University-Industry Collaboration Programme (UICP), Innovation and Technology Commission, the Government of the Hong Kong Special Administrative Region (No.: UIM/368); Ma Pak Leung Co., Ltd. (No.: RMGS-2019-1-04); Guangdong Basic and Applied Basic Research Foundation (No.: 2019A1515011497 and 2020A1515111036) and HKBU Tier 1 and Tier 2 Start-up Grant (No.: RC-SGT2/19-20/SCI/008).
Funding Information:
Conflict of Interest: The authors declare that this study received funding from Ma Pak Leung Co., Ltd. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.
Copyright © 2021 Zhang, Jiang, Wang, Lin, Zhang, Zhang, Zhu, Ng, Qu, Sze and Yung.
PY - 2021/4/16
Y1 - 2021/4/16
N2 - 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.
AB - 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.
KW - an-gong-niu-huang wan
KW - antioxidant properties
KW - cerebral ischemia
KW - GSK-3β/HO-1 pathway
KW - protective effect
UR - http://www.scopus.com/inward/record.url?scp=85105202087&partnerID=8YFLogxK
U2 - 10.3389/fphar.2021.640297
DO - 10.3389/fphar.2021.640297
M3 - Journal article
C2 - 33935731
AN - SCOPUS:85105202087
SN - 1663-9812
VL - 12
JO - Frontiers in Pharmacology
JF - Frontiers in Pharmacology
M1 - 640297
ER -