首页> 外文期刊>Frontiers in Pharmacology >The Ethanolic Extract of Caesalpinia sappan Heartwood Inhibits Cerebral Ischemia/Reperfusion Injury in a Rat Model Through a Multi-Targeted Pharmacological Mechanism
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The Ethanolic Extract of Caesalpinia sappan Heartwood Inhibits Cerebral Ischemia/Reperfusion Injury in a Rat Model Through a Multi-Targeted Pharmacological Mechanism

机译:ital仁心材的乙醇提取物通过多靶点药理学机制抑制大鼠模型的脑缺血/再灌注损伤。

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Background: Caesalpinia sappan L. ( C. sappan ) is a traditional Chinese medicinal plant. The dried heartwood of C. sappan (also known as Sappan wood) has been widely used for the folkloric medical treatment of ischemic cerebral stroke in China. However, the detailed underlying pharmacological mechanism still remains largely unexplored. Methods: In this study, a middle cerebral artery occlusion (MCAO) rat model was employed to elucidate the mechanism of the anti-cerebral ischemic effects of C. sappan ethanolic extract (CEE). Moreover, systemic multi-target identification coupled with gene ontology biological process (GO BP) and reactome pathway analysis was used to investigate the potential neuroprotective mechanism. Furthermore, the presumed mechanism was confirmed through biological analysis by determining the effects of CEE on the identified signaling pathways in PC12 cells model-induced by oxygen-glucose deprivation/reperfusion (OGD/R). Results: Our study demonstrates that CEE (both through in vivo administration at a dosage of 300 mg/kg and through in vitro incubation at a dosage of 2.4 μg/mL) is a neuroprotective agent that can effectively inhibit neuronal damage, promote synaptic generation, and suppress the activation of neutrophils, microglia, and astrocytes. Moreover, the neuroprotective mechanism of CEE is mediated via regulating 150 potential target proteins, which are associated with 6 biological processes and 10 pathways, including JAK-STAT, HSP90 and DNA damage/telomere stress. Conclusion: CEE can exert neuroprotective effect through multi-target pharmacological mechanisms to prevent ischemia/reperfusion-induced cerebral injury.
机译:背景:南美白es(Cesalpinia sappan L.)是中国传统的药用植物。 C. sappan的干燥心材(也称为Sappan木材)在中国已广泛用于民间治疗缺血性脑卒中。但是,详细的潜在药理机制仍在很大程度上尚待探索。方法:在本研究中,采用大脑中动脉阻塞(MCAO)大鼠模型阐明了C. sappan乙醇提取物(CEE)的抗脑缺血作用的机制。此外,系统的多目标识别结合基因本体生物学过程(GO BP)和反应组通路分析被用来研究潜在的神经保护机制。此外,通过确定CEE对氧-葡萄糖剥夺/再灌注(OGD / R)诱导的PC12细胞模型中已确定信号通路的影响,通过生物学分析证实了推测的机制。结果:我们的研究表明,CEE(通过以300 mg / kg的剂量进行体内给药和以2.4μg/ mL的剂量进行体外培养)是一种神经保护剂,可以有效抑制神经元损伤,促进突触生成,并抑制中性粒细胞,小胶质细胞和星形胶质细胞的活化。此外,CEE的神经保护机制是通过调节150种潜在的靶蛋白介导的,这些蛋白与6种生物学过程和10种途径相关,包括JAK-STAT,HSP90和DNA损伤/端粒应激。结论:CEE可以通过多靶点药理机制发挥神经保护作用,预防缺血/再灌注引起的脑损伤。

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