Neuroprotective effect of borneol combined with astragaloside Ⅳ and Panax notoginseng saponins in cerebral ischemia reperfusion injury rat model through Notch signaling pathway
【Abstract】 Objective To observe the neuroprotective effect of borneol combined with astragaloside Ⅳ (AST Ⅳ) and Panax notoginseng saponins (PNS) on rat models with cerebral ischemia reperfusion injury (CIRI) from the perspective of the Notch signaling pathway. Methods SD rats were randomly divided into the sham operation group, model group, borneol (7.5 mg/kg) group, AST Ⅳ (25 mg/kg) group, PNS (10 mg/kg) group, AST Ⅳ (10 mg/kg) + PNS (25 mg/kg) group, low-dose borneol (7.5 mg/kg) + AST Ⅳ (25 mg/kg) + PNS (10 mg/kg) group, high-dose borneol (15 mg/kg) + AST Ⅳ (20 mg/kg) + PNS (50 mg/kg) group and edaravone (4 mg/kg) group. Rats in the sham operation and model groups received intragastric administration of 0.5% CMC-Na (10 mL/kg); those in the edaravone group received edaravone (2.5 mL); the ones in the remaining administration groups were treated with 2.5 mL of the corresponding drugs by gavage. The medication was provided twice per day at a 12-h interval. The right middle cerebral artery of the rat was occluded by a suture 2 h after the last administration to establish the CIRI model. After 2 h of ischemia and 22 h of reperfusion, the neurological deficit scoring was conducted and pathological changes in the ischemic cortex of rats were observed after HE staining. The protein expression levels of neuron-specific nuclear (NeuN) and endothelial barrier antigen (EBA) in the ischemic cortex were detected by immunohistochemistry. The protein expression levels of vascular endothelial growth factor (VEGF), Notch1, and the intracellular domain of Notch (NICD) in the ischemic cortex were detected by Western blotting. Results The neurological deficit score and cell damage rate in the model group were significantly increased (P < 0.01); the neurological deficit score and cell damage rate in each administration group were significantly reduced (P < 0.05, 0.01), and the effect of borneol + AST Ⅳ + PNS was better than that of any single drug or AST Ⅳ + PNS (P < 0.05, 0.01). NeuN and EBA protein expression levels were significantly decreased in the ischemic cortex of the model group (P < 0.01), while those in each administration group were significantly enhanced (P < 0.05, 0.01). The effect of borneol + AST Ⅳ + PNS was better than that of any single drug or AST Ⅳ + PNS (P < 0.05, 0.01). In the model group, VEGF protein expression was increased significantly (P < 0.05), while NICD and Notch1 protein expression levels had no significant change. The protein expression levels of VEGF, NICD, and Notch1 were significantly up-regulated in the borneol + AST Ⅳ + PNS group (P < 0.01), and the effect of the combination of three drugs was better than that of any single drug or AST Ⅳ + PNS (P < 0.05, 0.01). Conclusion Borneol, AST Ⅳ, and PNS have the effects of preventing neuronal and cerebral microvascular damage after CIRI, and the protective effect of their combination against cerebral ischemic injury was better than that of any single drug or AST Ⅳ + PNS, which might be related to the activation of the Notch signaling pathway and the up-regulation of VEGF expression.
【Keywords】 borneol; astragaloside Ⅳ; Panax notoginseng saponins; cerebral ischemia reperfusion injury; neurons; microvascular;
(Translated by SUI T)
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