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复方龙脉宁治疗心肌梗死的活性成分及药理机制探索

Exploration of the active components and pharmacological mechanism of Compound Longmaining for the treatment of myocardial infarction.

作者信息

Li Jia, Wang Xiao, Bu Diaodiao, Zou Junbo, Xun Shining, Wang Yao, Jia Yanzuo, Yu Shangshang, Wang Wenfei, Zheng Jiahui, Hou Jiejun, Zhang Xiaofei, Wang Changli

机构信息

Department of Pharmaceutics, College of Pharmacy, Shaanxi University of Chinese Medicine, 712000 Xianyang, Shaanxi, China.

Affiliated Hospital of Shaanxi University of Chinese Medicine, 712000 Xianyang, Shaanxi, China.

出版信息

Front Biosci (Landmark Ed). 2021 Oct 30;26(10):813-827. doi: 10.52586/4990.

DOI:10.52586/4990
PMID:34719208
Abstract

: Myocardial Infarction (MI) is a cardiovascular disease with a high morbidity and mortality rate. While MI is currently treated with pharmaceuticals, there is a need for new treatment options: compound Chinese medicines may have unique advantages for the treatment of MI. : A combination of network pharmacology and experimental verification is used to identify the ingredients and mechanism of Compound Longmaining (CLMN) for treating MI. Network pharmacology combined with the gene expression omnibus (GEO) chip method is used to analyze the primary pathway of CLMN for treating MI, and then molecular docking is used to verify the affinity of key target proteins in the primary pathway that bind to active molecules. The major active compounds of CLMN are screened using the docking score results. The CIBERSORT algorithm is used to evaluate immune cell infiltration in MI, and high performance liquid chromatography (HPLC) is used to control the quality of the components. Finally, a mouse model is established to verify the molecular mechanism of CLMN for treating MI using hematoxlyn eosin (HE) staining and immunohistochemistry. : By utilizing network pharmacology combined with molecular docking, the mechanism of action of CLMN for the treatment of MI was found to possibly be related to the ingredients of puerarin, daidzein, ferulic acid, chrysin, and galangin. These molecules regulate the NF-Kappa B signaling pathway and the expression of , , , and other targets. The CIBERSORT algorithm and ggplot2 package analysis were used to distinguish the immune cells, such as neutrophils, macrophages, and T cells, that play a key role in the development of MI. HPLC controlled the quality of the screened medicinal ingredients. An immunohistochemical analysis showed that the and expression levels in MI of the CLMN-treated mice were decreased, while was increased. HE staining showed CLMN reduced inflammation in mouse cardiomyocytes and decreased fibrosis. : This study showed that CLMN treatment of MI is a process that involves multi-components, multi-targets and multi-pathways, and the established multi-index component content measurement of the CLMN decoction can be used for quality control of CLMN.

摘要

心肌梗死(MI)是一种发病率和死亡率都很高的心血管疾病。虽然目前MI的治疗采用药物治疗,但仍需要新的治疗选择:复方中药可能在MI的治疗中具有独特优势。:采用网络药理学与实验验证相结合的方法,确定复方龙脉宁(CLMN)治疗MI的成分和作用机制。运用网络药理学结合基因表达综合数据库(GEO)芯片方法分析CLMN治疗MI的主要途径,然后通过分子对接验证主要途径中关键靶蛋白与活性分子结合的亲和力。利用对接评分结果筛选CLMN的主要活性化合物。采用CIBERSORT算法评估MI中的免疫细胞浸润情况,并采用高效液相色谱法(HPLC)控制成分质量。最后,建立小鼠模型,通过苏木精-伊红(HE)染色和免疫组织化学验证CLMN治疗MI的分子机制。:通过网络药理学与分子对接相结合的方法,发现CLMN治疗MI的作用机制可能与葛根素、大豆苷元、阿魏酸、白杨素和高良姜素等成分有关。这些分子调节核因子-κB信号通路以及、、等靶点的表达。采用CIBERSORT算法和ggplot2软件包分析来区分在MI发生发展中起关键作用的免疫细胞,如中性粒细胞、巨噬细胞和T细胞。HPLC控制筛选出的药用成分的质量。免疫组织化学分析显示,CLMN治疗的小鼠MI中、的表达水平降低,而升高。HE染色显示CLMN减轻了小鼠心肌细胞的炎症并减少了纤维化。:本研究表明,CLMN治疗MI是一个涉及多成分、多靶点和多途径的过程,所建立的CLMN汤剂多指标成分含量测定方法可用于CLMN的质量控制。

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