Network Pharmacology Study of Astragaloside Ⅳ in Treatment of Ischemic Stroke / 中国实验方剂学杂志

Objective:To study the mechanism of astragaloside Ⅳ in the treatment of ischemic stroke by means of network pharmacology. Method:The targets of astragaloside Ⅳ were predicted using Swiss Target Prediction platform， and the targets of ischemic stroke were retrieved using GeneCards， Therapeutic Target Database （TTD）， Traditional Chinese Medicine Integrated Database （TCMID） and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） databases. The potential targets of astragaloside Ⅳ acting on ischemic stroke were obtained by the intersection of the targets of astragaloside Ⅳ and ischemic stroke. STRING platform was used to build protein-protein interaction （PPI） network， and eigenvalues were calculated through network topology analysis to screen core targets. Gene Ontology （GO） analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway analysis were performed on the related targets in DAVID database. Finally， molecular docking verification was conducted to further clarify the core targets of astragaloside Ⅳ acting on ischemic stroke. Result:The 44 common targets were obtained after the intersection of the targets of astragaloside Ⅳ and ischemic stroke. PPI network topology analysis showed that RAC-alpha serine/threonine-protein kinase （Akt1）， renin （REN）， epidermal growth factor receptor （EGFR）， vascular endothlial growth factor A （VEGFA） and neuronal proto-oncogene tyrosine-protein kinase （SRC） were the core targets of astragaloside Ⅳ in the treatment of ischemic stroke. Enrichment analysis results of KEGG pathway showed that the pathways of astragaloside Ⅳ acting on ischemic stroke involved the neuroactive ligand-receptor interaction pathway， cGMP-PKG signaling pathway， calcium signaling pathway， Rap1 signaling pathway， PI3K/Akt signaling pathway， etc. Conclusion:Astragaloside Ⅳ may promote angiogenesis and inhibit platelet activity by acting on Akt1， REN， EGFR， VEGFA， SRC， thus improving cerebral blood flow. It can also inhibit the apoptosis of ischemic brain tissue cells and inflammation to reduce the damage of nerve function， and finally treat ischemic stroke. This study provides ideas and guidance for further exploring the mechanism of astragaloside Ⅳ in the treatment of ischemic stroke.

Effect of neutrophil extracellular traps on ischemic stroke and intervention of traditional Chinese medicine / 中国中药杂志

Ischemic stroke is the leading cause of death and disability in adults in China. Recent studies have shown that neutrophil extracellular traps play a crucial role in occurrence and development of ischemic stroke. This paper reviewed the literatures on NETs since the discovery of NETs more than a decade ago, and summarized the composition of NETs, the effects of NETs on stroke, the intervention targets of NETs, and the effects of traditional Chinese medicine on NETs. NETs are an important cause of brain injury after stroke. Platelets, peptidylarginine deiminase 4, reactive oxygen species and histones are the targets to regulate NET formation in stroke. There are few researches on traditional Chinese medicine targeting NETs for stroke. Studies on the intervention of traditional Chinese medicine mainly target on neutrophils, which are the main components of NETs, and platelets, which induce the formation of NETs. The paper provided a comprehensive overview of current studies of NETs in ischemic stroke, so as to provide new ideas for the treatment and drug development of ischemic stroke.

Naoxintong Inhibits LPS Induced BV2 Cell Pyroptosis by NLRP3/Caspase-1 Signaling Pathway / 中国实验方剂学杂志

Objective::To explore the effect of Naoxintong ethanol extract (NXT) on pyroptosis of BV2 microglia cells induced by lipopolysaccharide (LPS), and to explain the mechanism of pyroptosis based on NOD like receptor thermoprotein domain 3 (NLRP3)/cysteine-proteinase-1 (Caspase-1) pathway. Method::BV2 cells was treated with different concentrations of NXT(2, 10, 50 mg·L-1) after induced by LPS(1 mg·L-1) in vitro. Real-time PCR was used to detect mRNA expression of pro-inflammatory cytokine such as interleukin 1 beta (IL-1β), tumor necrosis factor (TNF)-α, and NLRP3.Western bolt and immunofluorescence were used to observe the protein expression of NLRP3/Caspase-1 signaling pathway. Result::Compared with control group, after LPS(1 mg·L-1) stimulation, BV2 cells viability was decreased. The mRNA expression levels of IL-1β, TNF-α and NLRP3 were significantly elevated(P<0.01), the protein levels of NLRP3 and Caspase-1 p20/Caspase-1 were also increased. After given NXT(2, 10, 50 mg·L-1), BV2 cells viability reversed which induced by LPS. Compared with LPS group, the mRNA expression of IL-1β, TNF-α and NLRP3 reduced obviously with given 50 mg·L-1NXT (P<0.05, P<0.01), significantly inhibited NLRP3 high protein expression and Caspase-1 p20/Caspase-1 expression(P<0.01). Conclusion::NXT can inhibit LPS induced pyroptosis of BV2 cells and the mechanism may closely related to NLRP3/Caspase-1 signaling pathway.