Protective Effect of An-Gong-Niu-Huang Wan Pre-treatment Against Experimental Cerebral Ischemia Injury via Regulating GSK-3β/HO-1 Pathway

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.

Oleanolic Acid Alleviates Cerebral Ischemia/Reperfusion Injury via Regulation of the GSK-3β/HO-1 Signaling Pathway

“…MCAO was induced after the third administration of OA as described in our previous report [36]. Briefly, rats were anesthetized by 3% isoflurane inhalation (1.5 L/min).…”

“…Neurological function was analyzed 6 days after reperfusion using the Zea-Longa score, as described previously [36]. The Zea-Longa score ranges from 0 to 4 (0: no obvious impairment; 1: inextensibility of the contralateral forepaw; 2: circling to the contralateral side; 3: leaning to the contralateral side; 4: disability to walk spontaneously).…”

Yi-Zhi-Fang-Dai Formula Exerts Neuroprotective Effects Against Pyroptosis and Blood–Brain Barrier–Glymphatic Dysfunctions to Prevent Amyloid-Beta Acute Accumulation After Cerebral Ischemia and Reperfusion in Rats

“…Experimental studies revealed that BHD and TXL could alleviate cerebral I/R injury and exert protective effects on the BBB ( Liu et al, 2013 ; Chen et al, 2019 ). In studies about the therapeutic efficacy of TCM compound medicines or extracts, such as BHD and TXL mentioned above for cerebral I/R injury, drug administration for 3–7 days starting before MCAO is the common means to enhance intervention effects ( Liu et al, 2013 ; Yu et al, 2018 ; Chen et al, 2019 ; She et al, 2019 ; Zheng et al, 2019 ; Zhang S. et al, 2021 ). Accordingly, based on these literatures, we select YZFDF pretreatment to carry out the present study.…”

Muscone and (+)-Borneol Cooperatively Strengthen CREB Induction of Claudin 5 in IL-1β-Induced Endothelium Injury

“…The Angong Niuhuang Pill (ANP) is a well-known classical prescription of traditional Chinese medicine (TCM), widely used for the management of acute cerebrovascular diseases such as ischemia stroke, intracerebral hemorrhage, and traumatic brain damage [ 17 , 18 ], having the role to prevent neural apoptosis and neurological deficits [ 19 ]. Meanwhile, its protective effects on tight junction proteins have been documented [ 20 ].…”