The combination of Astragalus membranaceus and ligustrazine mitigates cerebral ischemia-reperfusion injury via regulating NR2B-ERK/CREB signaling

作者：Tang, Xialing; Xie, Shanshan; Wang, Huajun; Li, Yingbin; Lai, Zhiyu; Sun, Shuangxi; Pan, Ruanhuan; Huang, Yan^*; Cai, Jun^*

来源：Brain and Behavior, 2023, 13(2).

DOI：10.1002/brb3.2867

• Astragalus membranaceus
• cerebral ischemia-reperfusion injury
• ligustrazine
• N-methyl-D-aspartate receptors
• stroke

Background and purposeCerebral ischemia-reperfusion (I/R) injury is a major factor underlying the high mortality and morbidity rates in stroke patients. Our previous study found that the combination of Astragalus membranaceus extract and ligustrazine (Ast+Lig) treatment could protect brain tissues against inflammation in rats with thrombolytic cerebral ischemia. Activation of N-methyl-D-aspartate receptors (NMDAR) is implicated in brain damage induced by cerebral I/R injury. MethodsWe used in vivo and in vitro models of cerebral I/R injury for middle cerebral artery occlusion/reperfusion in mice and oxygen-glucose deprivation/reoxygenation in primary rat cerebral cortical neurons to evaluate the protective effects of Ast+Lig on cerebral I/R injury, and whether the protective mechanism was related to the regulation of NMDAR-ERK/CREB signaling. ResultsTreatment with Ast+Lig, or MK-801 (an inhibitor of NMDAR) significantly ameliorated neurological deficits, decreased infarct volumes, suppressed neuronal damage and Ca2+ influx, and maintained the mitochondrial membrane potential in vivo and in vitro following cerebral I/R injury based on 2,3,5-triphenyl tetrazolium chloride staining, immunohistochemistry, and immunofluorescent staining. Furthermore, treatment with Ast+Lig evidently prevented the upregulation of NR2B, but not NR2A, in vivo and in vitro following cerebral I/R injury based on western blotting and reverse transcription-quantitative PCR analyses. Moreover, treatment with Ast+Lig significantly increased the phosphorylation of ERK and CREB, as well as increasing their mRNA expression levels in vivo and in vitro following cerebral I/R injury. ConclusionsThe overall results thus suggest that the Ast+Lig combination conferred neuroprotective properties against cerebral I/R injury via regulation of the NR2B-ERK/CREB signaling pathway.

• 单位
  广州大学; 广东省人民医院; y; 广州中医药大学