Background: Atherosclerosis (AS) is the leading cause of cardiovascular diseases, such as myocardial infarction and stroke. Guanmaitong granule (GMTG) is a TCM (Traditional Chinese medicine) prescribed to treat AS. However, its mechanism remains unclear.
Methods: We obtained reliable ingredients and targets of GMTG using the HERB database. AS-related targets were obtained from HERB and GeneCards databases. The target database was constructed by intersecting the ingredients of GMTG with the AS-related targets. STRING and Cytoscape were used to create protein-protein interaction (PPI) network and screen core targets. GO enrichment analysis and KEGG pathway analyses were performed using R. Finally, the ApoE^−/− mice AS model was induced by a high-fat diet (HFD) for in vivo validation of core pathways and targets.
Results: A total of 124 ingredients and 418 potential targets of GMTG for treating AS were obtained. Numerous ingredients and targets were related to Panax notoginseng, Salvia miltiorrhiza, and Astragalus. Most core targets and pathways were involved in the inflammatory immune response. GMTG could decrease serum triglycerides, total cholesterol, low-density lipoprotein-cholesterol, and oxidized low-density lipoprotein level and increase the serum high-density lipoprotein-cholesterol level. Furthermore, GMTG reduced the plaque burden and promoted plaque remodeling by reducing plaque area, lipid deposition, foam cell content, and collagen fiber content in the plaque in the aortic root of ApoE^−/− mice. GMTG inhibited systemic and plaque inflammatory immune response and increased plaque stability by inhibiting the excessive release of the TLR4/MyD88/NF-κB pathway-induced inflammatory cytokines, tumor necrosis factor, interleukin-6, and interleukin-1 beta.
Conclusion: Radix notoginseng, Radix salviae liguliobae, and Radix astragali are the main ingredients of GMTG for treating AS. Further, GMTG could regulate the level of serum lipids and inhibit inflammatory immune response, which resulted in anti-AS effects such as plaque stabilization, reduction of plaque burden, and plaque remodeling. GMTG is a promising multi-target treatment for AS.



中文翻译：

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冠脉通颗粒通过抑制 ApoE−/− 高脂饮食小鼠的炎症免疫反应来减轻动脉粥样硬化

背景：动脉粥样硬化（AS）是心血管疾病的主要原因，如心肌梗塞和中风。冠脉通颗粒（GMTG）是一种用于治疗AS的中药（中药）。然而，其机制仍不清楚。
方法：我们使用HERB数据库获得了GMTG的可靠成分和靶点。AS 相关靶点来自 HERB 和 GeneCards 数据库。目标数据库是通过将 GMTG 的成分与 AS 相关的目标相交来构建的。STRING 和 Cytoscape 用于创建蛋白质-蛋白质相互作用 (PPI) 网络和筛选核心目标。使用 R 进行 GO 富集分析和 KEGG 通路分析。最后，ApoE ^-/-小鼠 AS 模型由高脂饮食 (HFD) 诱导，用于体内验证核心途径和靶点。
结果：共获得 GMTG 治疗 AS 的 124 种成分和 418 个潜在靶点。许多成分和目标都与三七、丹参和黄芪有关. 大多数核心靶点和途径都参与了炎症免疫反应。GMTG可降低血清甘油三酯、总胆固醇、低密度脂蛋白胆固醇和氧化低密度脂蛋白水平，提高血清高密度脂蛋白胆固醇水平。^{此外，GMTG 通过减少 ApoE -/-}小鼠主动脉根部斑块中的斑块面积、脂质沉积、泡沫细胞含量和胶原纤维含量来减少斑块负荷并促进斑块重塑。GMTG 通过抑制 TLR4/MyD88/NF-κB 通路诱导的炎性细胞因子、肿瘤坏死因子、白细胞介素 6 和白细胞介素 1 β 的过度释放来抑制全身和斑块炎症免疫反应并增加斑块稳定性。
结论： 三七、丹参、黄芪是灵芝治疗AS的主要成分。此外，GMTG 可以调节血脂水平并抑制炎症免疫反应，从而产生抗 AS 作用，如斑块稳定、减少斑块负荷和斑块重塑。GMTG 是一种很有前途的 AS 多靶点治疗方法。