Network pharmacology-based strategy to investigate pharmacological mechanisms of Andrographolide for treatment of vascular cognitive impairment
Network pharmacology-based strategy to investigate pharmacological mechanisms of Andrographolide for treatment of vascular cognitive impairment
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基于网络药理学的策略研究穿心莲内酯治疗血管性认知障碍的药理机制
DOI：
10.1016/j.intimp.2022.108756
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发表时间：
2022
影响因子：
5.6
通讯作者：
Jianliang Fu
中科院分区：
文献类型：
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作者：
Yao Zhao;Jiawei Zhang;Yaxuan Zhang;Yueqi Zhang;Xiaojie Zhang;Yaling Zheng;Hongmei Wang;Xiuzhe Wang;Jianliang Fu
血管性认知障碍（VCI）是痴呆的第二种最常见形式。穿心莲在抗炎、抗氧化应激、抗细胞凋亡等方面具有潜在的作用。通过网络药理学分析，我们获得了48个与Andro抗VCI作用相关的潜在基因。利用GO和京都基因和基因组百科全书（KEGG）分析，发现潜在基因的富集途径，筛选出丝裂原活化蛋白激酶（MAPK）途径。为了验证网络药理学的结果，我们测试了Andro在双侧颈总动脉闭塞（BCCAO）手术诱导的VCI模型中的作用。结果表明，Andro治疗可改善BCCAO所致的认知障碍。免疫组化结果显示，Andro可减轻BCCAO大鼠大脑皮层和海马神经元的损伤和小胶质细胞的活化。为了检测MAPK通路的变化，我们分析了JNK，p38和ERK的表达，发现Andro降低了BCCAO大鼠磷酸化ERK（p-ERK）和磷酸化p38（p-p38）的水平。总之，Andro可以改善VCI患者的神经元存活，减轻神经炎症，改善认知功能障碍。Andro治疗的潜在机制可能是通过抑制MAPK通路。
Vascular cognitive impairment (VCI) is the second most common form of dementia. Andrographolide (Andro) shows potential effects in anti-inflammation, anti-oxidative stress, and anti-apoptosis. We have obtained 48 potential genes related to the effect of Andro on VCI through network pharmacology analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were used to reveal significant enriched pathway of potential genes, and the mitogen-activated protein kinase (MAPK) pathway was screened out. To verify the results of network pharmacology, we tested the effects of Andro in VCI model induced by bilateral common carotid artery occlusion (BCCAO) surgery. The results showed that Andro treatment ameliorated the cognitive impairment induced by BCCAO. Immunohistochemistry study revealed that Andro could reduce neuronal damage and activation of microglia in the cortex and hippocampus in BCCAO rats. To test the MAPK pathway changes, we analyzed the expression of JNK, p38 and ERK and found that Andro reduced the levels of phosphorylated-ERK (p-ERK) and phosphorylated-p38 (p-p38) in BCCAO rats. In conclusion, Andro could improve neuronal survival, reduce neuroinflammation and ameliorate cognitive impairment in VCI. The underlying mechanisms of Andro treatment may be through the inhibition of MAPK pathway.