Danshen-Chuanxiongqin Injection attenuates cerebral ischemic stroke by inhibiting neuroinflammation via the TLR2/ TLR4-MyD88-NF-κB Pathway in tMCAO mice  

作　　者：XU Xiao-Jing LONG Jin-Bo JIN Kai-Yu CHEN Li-Bing LU Xiao-Yan FAN Xiao-Hui 

机构地区：[1]Pharmaceutical Informatics Institute,College of Pharmaceutical Sciences,Zhejiang University,Hangzhou 310058,China [2]State Key Laboratory of Component-Based Chinese Medicine,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China

出　　处：《Chinese Journal of Natural Medicines》2021年第10期772-783,共12页中国天然药物（英文版）

基　　金：supported by the National S&T Major Project(No.2018ZX09201011);the National Youth Topnotch Talent Support Program(No.W02070098).

摘　　要：Danshen-Chuanxiongqin Injection(DCI)is a commonly used traditional Chinese medicine for the treatment of cerebral ischemic stroke in China.However,its underlying mechanisms remain completely understood.The current study was designed to explore the protective mechanisms of DCI against cerebral ischemic stroke through integrating whole-transcriptome sequencing coupled with network pharmacology analysis.First,using a mouse model of cerebral ischemic stroke by transient middle cerebral artery occlusion(tMCAO),we found that DCI(4.10 mL·kg−1)significantly alleviated cerebral ischemic infarction,neurological deficits,and the pathological injury of hippocampal and cortical neurons in mice.Next,the whole-transcriptome sequencing was performed on brain tissues.The cerebral ischemia disease(CID)network was constructed by integrating transcriptome sequencing data and cerebrovascular disease-related genes.The results showed CID network was imbalanced due to tMCAO,but a recovery regulation was observed after DCI treatment.Pathway analysis of the key genes with recovery efficiency showed that the neuroinflammation signaling pathway was highly enriched,while the TLR2/TLR4-MyD88-NF-κB pathway was predicted to be affected.Consistently,the in vivo validation experiments confirmed that DCI exhibited protective effects against cerebral ischemic stroke by inhibiting neuroinflammation via the TLR2/TLR4-MyD88-NF-κB pathway.More interestingly,DCI markedly suppressed the neutrophils infiltrated into the brain parenchyma via the choroid plexus route and showed anti-neuroinflammation effects.In conclusion,our results provide dependable evidence that inhibiting neuroinflammation via the TLR2/TLR4-MyD88-NF-κB pathway is the main mechanism of DCI against cerebral ischemic stroke in mice.

关 键 词：Danshen-Chuanxiongqin Injection Cerebral ischemic stroke Network pharmacology NEUROINFLAMMATION NEUTROPHIL Choroid plexus 

分 类 号：R965[医药卫生—药理学]