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运用网络药理学结合多变量数据分析揭示蒸制(药物名称缺失,推测为某药物)补血作用的活性成分及潜在靶点

Unveiling Active Constituents and Potential Targets Related to the Hematinic Effect of Steamed Using Network Pharmacology Coupled With Multivariate Data Analyses.

作者信息

Xiong Yin, Hu Yupiao, Chen Lijuan, Zhang Zejun, Zhang Yiming, Niu Ming, Cui Xiuming

机构信息

Faculty of Life Science and Technology, Kunming University of Science and Technology, Kunming, China.

Yunnan Key Laboratory of Panax Notoginseng, Kunming, China.

出版信息

Front Pharmacol. 2019 Jan 8;9:1514. doi: 10.3389/fphar.2018.01514. eCollection 2018.

Abstract

Steamed (SPN) has been used as a tonic to improve the blood deficiency syndrome (BDS) in the theory of traditional Chinese medicine. Here, we aim to unveil active constituents and potential targets related to the hematinic effect of SPN, which has not been answered before. In the study a constituent-target-disease network was constructed by combining the SPN-specific and anemia-specific target proteins with protein-protein interactions. And the network pharmacology was used to screen out the underlying targets and mechanisms of SPN treating anemia. Also, the multivariate data analyses were performed for the double screening. According to the results, 11 targets related to chemical constituents of SPN were found to be closely associated with the hematinic effect of SPN. Among them, the direct target protein of mitochondrial ferrochelatase (FECH) had the major role through the metabolic pathway. Meanwhile, Rk and 20()-Rg were predicted to be major constituents related to the hematinic effect of SPN by both multivariate data analyses and network pharmacology. And it was been validated by the pharmacologic tests that Rk and 20()-Rg could significantly increase the levels of blood routine parameters, FECH and its downstream protein of heme in mice with BDS. The study provides evidences for the mechanism understanding and drug development of SPN for the treatment of anemia.

摘要

在传统中医理论中,蒸制(SPN)被用作一种滋补品来改善血虚证(BDS)。在此,我们旨在揭示与SPN补血作用相关的活性成分和潜在靶点,这在之前尚未得到解答。在该研究中,通过将SPN特异性和贫血特异性靶蛋白与蛋白质 - 蛋白质相互作用相结合,构建了一个成分 - 靶点 - 疾病网络。并且利用网络药理学筛选出SPN治疗贫血的潜在靶点和机制。此外,还进行了多变量数据分析以进行双重筛选。根据结果,发现与SPN化学成分相关的11个靶点与SPN的补血作用密切相关。其中,线粒体铁螯合酶(FECH)的直接靶蛋白通过代谢途径起主要作用。同时,通过多变量数据分析和网络药理学预测Rk和20() - Rg是与SPN补血作用相关的主要成分。并且通过药理学试验验证,Rk和20() - Rg可显著提高BDS小鼠血常规参数、FECH及其血红素下游蛋白的水平。该研究为理解SPN治疗贫血的机制和药物开发提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/172e/6331451/19358ac163bb/fphar-09-01514-g001.jpg

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