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Identifying the molecular targets of Salvia miltiorrhiza (SM) in ox-LDL induced macrophage-derived foam cells based on the integration of metabolomics and network pharmacology

机译:基于代谢组和网络药理学的整合,鉴定Salvia Miltiorrhiza(SM)的Salvia Miltiorrhiza(SM)的分子靶标

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摘要

The identification of network targets is one of the core issues used to reveal the molecular mechanism of traditional Chinese medicine (TCM) and is also the grand challenge of modernization of TCM. In this study, a protein-protein interaction (PPI) network was constructed based on the integration of network pharmacology and metabolomics, which was used as an effective approach to elucidate the relationship between disease pathway proteins and the targets of active small-molecule compounds. The intermolecular transfer process of the drug effect of active compounds in Salvia miltiorrhiza (SM) was revealed and visualized using the PPI network. Our study indicates that PTGS2 was the most important disease protein regulated by the active compounds in SM. Furthermore, the drug targets that can be linked to PTGS2 were regarded as direct targets and the direct targets of the active compounds were identified, respectively. Western blot and co-immuno precipitation (Co-IP) were used to verify the results of the network analysis and reveal the intermolecular transfer process of the effect of Tan IIA. Biological validation revealed that Tan IIA-EDN1-PTGS2-anandamide was a major intervention way of Tan IIA on early atherosclerosis (AS). This work provides a new perspective for the discovery of drug targets and the specific approaches regulated by the active compounds in SM on disease pathway proteins, which is beneficial for understanding the mechanism of action of bioactive compounds and expanding their clinical applications.
机译:网络目标的识别是用于揭示中医(TCM)的分子机制的核心问题之一,也是中医现代化的大挑战。在该研究中,基于网络药理学和代谢组科的整合构建了蛋白质 - 蛋白质相互作用(PPI)网络,其用作阐明疾病途径蛋白与活性小分子化合物的靶标的有效方法。使用PPI网络揭示并可视化了丹参中活性化合物的分子转移过程的丹参(SM)。我们的研究表明,PTGS2是SM中活性化合物调节的最重要的疾病蛋白。此外,可以与PTGS2连接的药物靶标被认为是直接靶标,并分别鉴定活性化合物的直接靶标。 Western印迹和共免疫沉淀(CO-IP)用于验证网络分析的结果,并揭示Tan Iia效果的分子间转移过程。生物验证显示,Tan Iia-Edn1-PTGS2- anandamide是Tan Iia在早期动脉粥样硬化(AS)的主要干预方式。这项工作为发现药物靶标和由疾病途径蛋白的SM中的活性化合物调节的特定方法提供了新的视角,这有利于理解生物活性化合物的作用机制并扩大其临床应用。

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  • 来源
    《RSC Advances》 |2018年第7期|共8页
  • 作者单位

    China Acad Chinese Med Sci Inst Chinese Mat Med Beijing 100700 Peoples R China;

    Beijing Univ Chinese Med Res Ctr Chinese Med Anal &

    Transformat Beijing 100029 Peoples R China;

    Beijing Univ Chinese Med Res Ctr Chinese Med Anal &

    Transformat Beijing 100029 Peoples R China;

    China Acad Chinese Med Sci Inst Chinese Mat Med Beijing 100700 Peoples R China;

    Beijing Univ Chinese Med Res Ctr Chinese Med Anal &

    Transformat Beijing 100029 Peoples R China;

    Beijing Univ Chinese Med Res Ctr Chinese Med Anal &

    Transformat Beijing 100029 Peoples R China;

    Beijing Univ Chinese Med Res Ctr Chinese Med Anal &

    Transformat Beijing 100029 Peoples R China;

    Beijing Univ Chinese Med Res Ctr Chinese Med Anal &

    Transformat Beijing 100029 Peoples R China;

    Beijing Univ Chinese Med Res Ctr Chinese Med Anal &

    Transformat Beijing 100029 Peoples R China;

    Beijing Univ Chinese Med Res Ctr Chinese Med Anal &

    Transformat Beijing 100029 Peoples R China;

    Beijing Univ Chinese Med Res Ctr Chinese Med Anal &

    Transformat Beijing 100029 Peoples R China;

    China Acad Chinese Med Sci Inst Chinese Mat Med Beijing 100700 Peoples R China;

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  • 正文语种 eng
  • 中图分类 化学;
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