Abstract：
BACKGROUND: Intracerebral hemorrhage (ICH) is a life-threatening stroke subtype with high rates of disability and mortality. Naoxueshu oral liquid is a proprietary Chinese medicine that absorbs hematoma and exhibits neuroprotective effects in patients with ICH. However, the underlying mechanisms remain obscure.
OBJECTIVE: Exploring and elucidating the pharmacological mechanism of Naoxueshu oral liquid in the treatment of ICH.
METHODS: The Gene Expression Omnibus (GEO) database was used to download the gene expression data on ICH. ICH-related hub modules were obtained by weighted gene co-expression network analysis (WGCNA) of differentially co-expressed genes (DEGs). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the obtained key modules to identify the ICH-related signaling pathways. Network pharmacology technology was applied to forecast the targets of Naoxueshu oral liquid and to establish a protein-protein interaction (PPI) network of overlapping targets between Naoxueshu oral liquid and ICH. Functional annotation and enrichment pathway analyses of the intersectional targets were performed using the omicsbean database. Finally, we verified the therapeutic role and mechanism of Naoxueshu oral liquid in ICH through molecular docking and experiments.
RESULTS: Through the WGCNA analysis, combined with network pharmacology, it was found that immune inflammation was closely related to the early pathological mechanism of ICH. Naoxueshu oral liquid suppressed the inflammatory response; hence, it could be a potential drug for ICH treatment. Molecular docking further confirmed that the effective components of Naoxueshu oral liquid docked well with CD163. Finally, the experimental results showed that Naoxueshu oral liquid treatment in the ICH rat model attenuated neurological deficits and neuronal injury, decreased hematoma volume, and promoted hematoma absorption. In addition, Naoxueshu oral liquid treatment also significantly increased the levels of Arg-1, CD163, Nrf2, and HO-1 around hematoma after ICH.
CONCLUSIONS: This study demonstrated that Naoxueshu oral liquid attenuated neurological deficits and accelerated hematoma absorption, possibly by suppressing inflammatory responses, which might be related to the regulation of Nrf2/CD163/HO-1 that interfered with the activation of M2 microglia, thus accelerating the clearance and decomposition of hemoglobin in the hematoma.
OBJECTIVE: Exploring and elucidating the pharmacological mechanism of Naoxueshu oral liquid in the treatment of ICH.
METHODS: The Gene Expression Omnibus (GEO) database was used to download the gene expression data on ICH. ICH-related hub modules were obtained by weighted gene co-expression network analysis (WGCNA) of differentially co-expressed genes (DEGs). The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted using the obtained key modules to identify the ICH-related signaling pathways. Network pharmacology technology was applied to forecast the targets of Naoxueshu oral liquid and to establish a protein-protein interaction (PPI) network of overlapping targets between Naoxueshu oral liquid and ICH. Functional annotation and enrichment pathway analyses of the intersectional targets were performed using the omicsbean database. Finally, we verified the therapeutic role and mechanism of Naoxueshu oral liquid in ICH through molecular docking and experiments.
RESULTS: Through the WGCNA analysis, combined with network pharmacology, it was found that immune inflammation was closely related to the early pathological mechanism of ICH. Naoxueshu oral liquid suppressed the inflammatory response; hence, it could be a potential drug for ICH treatment. Molecular docking further confirmed that the effective components of Naoxueshu oral liquid docked well with CD163. Finally, the experimental results showed that Naoxueshu oral liquid treatment in the ICH rat model attenuated neurological deficits and neuronal injury, decreased hematoma volume, and promoted hematoma absorption. In addition, Naoxueshu oral liquid treatment also significantly increased the levels of Arg-1, CD163, Nrf2, and HO-1 around hematoma after ICH.
CONCLUSIONS: This study demonstrated that Naoxueshu oral liquid attenuated neurological deficits and accelerated hematoma absorption, possibly by suppressing inflammatory responses, which might be related to the regulation of Nrf2/CD163/HO-1 that interfered with the activation of M2 microglia, thus accelerating the clearance and decomposition of hemoglobin in the hematoma.
摘要：
背景：脑出血（ICH）是一种危及生命的卒中亚型，具有高致残率和死亡率。脑血舒口服液是一种吸收血肿的中成药，对ICH患者具有神经保护作用。然而,潜在的机制仍然模糊。
目的：探讨脑血舒口服液治疗ICH的药理作用机制。
方法：使用基因表达综合（GEO）数据库下载ICH上的基因表达数据。通过差异共表达基因(DEGs)的加权基因共表达网络分析(WGCNA)获得ICH相关集线器模块。使用获得的关键模块进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)富集分析以鉴定ICH相关的信号传导途径。应用网络药理学技术预测脑血舒口服液的作用靶点,建立脑血舒口服液与ICH重叠作用靶点的蛋白-蛋白相互作用(PPI)网络。使用omicsbean数据库进行交叉靶标的功能注释和富集途径分析。最后,我们通过分子对接和实验验证了脑雪舒口服液在ICH中的治疗作用和机制。
结果：通过WGCNA分析，结合网络药理学，发现免疫炎症与ICH的早期病理机制密切相关。脑血舒口服液抑制炎症反应；因此，它可能是ICH治疗的潜在药物。分子对接进一步证实，脑雪舒口服液的有效成分与CD163对接良好。最后,实验结果表明,脑血舒口服液治疗ICH大鼠模型可减轻神经功能缺损和神经元损伤,血肿体积减少，促进血肿吸收。此外,脑血舒口服液治疗后血肿周围的Arg-1，CD163，Nrf2和HO-1水平也显着升高。
结论：本研究表明脑雪舒口服液减轻了神经功能缺损，加速了血肿吸收，可能是通过抑制炎症反应，这可能与Nrf2/CD163/HO-1的调节干扰M2小胶质细胞的激活有关，从而加速血肿中血红蛋白的清除和分解。
目的：探讨脑血舒口服液治疗ICH的药理作用机制。
方法：使用基因表达综合（GEO）数据库下载ICH上的基因表达数据。通过差异共表达基因(DEGs)的加权基因共表达网络分析(WGCNA)获得ICH相关集线器模块。使用获得的关键模块进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)富集分析以鉴定ICH相关的信号传导途径。应用网络药理学技术预测脑血舒口服液的作用靶点,建立脑血舒口服液与ICH重叠作用靶点的蛋白-蛋白相互作用(PPI)网络。使用omicsbean数据库进行交叉靶标的功能注释和富集途径分析。最后,我们通过分子对接和实验验证了脑雪舒口服液在ICH中的治疗作用和机制。
结果：通过WGCNA分析，结合网络药理学，发现免疫炎症与ICH的早期病理机制密切相关。脑血舒口服液抑制炎症反应；因此，它可能是ICH治疗的潜在药物。分子对接进一步证实，脑雪舒口服液的有效成分与CD163对接良好。最后,实验结果表明,脑血舒口服液治疗ICH大鼠模型可减轻神经功能缺损和神经元损伤,血肿体积减少，促进血肿吸收。此外,脑血舒口服液治疗后血肿周围的Arg-1，CD163，Nrf2和HO-1水平也显着升高。
结论：本研究表明脑雪舒口服液减轻了神经功能缺损，加速了血肿吸收，可能是通过抑制炎症反应，这可能与Nrf2/CD163/HO-1的调节干扰M2小胶质细胞的激活有关，从而加速血肿中血红蛋白的清除和分解。
