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基于网络药理学的研究揭示茜草抗肝癌作用的活性成分和机制

Network pharmacology-based research on the active component and mechanism of the antihepatoma effect of Rubia cordifolia L.

机构信息

Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China.

Key Laboratory of Traditional Chinese Medicine Resources and Chemistry of Hubei Province, Wuhan, China.

出版信息

J Cell Biochem. 2019 Aug;120(8):12461-12472. doi: 10.1002/jcb.28513. Epub 2019 Feb 28.

Abstract

Rubia cordifolia L. is widely used in Asia and its antihepatoma effect has been proved by in vitro and in vivo experiments. However, there are few studies on its specific mechanism. In the present study, the network pharmacology method was used to construct the component/target/pathway molecular regulatory network for the antihepatoma effect of Rubia cordifolia L. to explore the effective components of Rubia cordifolia L. and its potential mechanism. The chemical components of Rubia cordifolia L. were identified through literature and databases, and the components were evaluated and screened by drug likeness and pharmacokinetic characteristics (ADMET). The targets of active components were predicted according to the reverse pharmacophore matching model. The hepatic carcinoma-related genes were found in databases, and antihepatoma-related gene targets were selected through comparison. The functions of target genes and related pathways were analyzed and screened using the Database for Annotation, Visualization and Integrated Discovery, and the component/target/pathways network of antihepatoma effect of Rubia cordifolia L. was constructed using Cytoscape software. Finally, 16 active compounds were screened from Rubia cordifolia L., and 39 gene targets, including AKT1, mitogen-activated protein kinase 1, and epidermal growth factor receptor, were involved. Rubia cordifolia L. also affected the hepatitis B, phosphoinositide-3-kinase-protein kinase B, and mitogen-activated protein kinase signaling pathways. Many direct-acting tumor-related signaling pathways and indirect-acting hepatitis pathways inhibit the generation of liver cancer. The present study provided a scientific basis for further elucidating the mechanism of Rubia cordifolia L. against liver cancer.

摘要

茜草(Rubia cordifolia L.)在亚洲被广泛应用,其体外和体内实验均已证实具有抗肝癌作用。然而,关于其具体机制的研究较少。本研究采用网络药理学方法构建茜草抗肝癌作用的成分-靶标-通路分子调控网络,探讨茜草的有效成分及其潜在机制。通过文献和数据库鉴定茜草的化学成分,通过药物相似性和药代动力学特性(ADMET)对成分进行评价和筛选。根据反向药效团匹配模型预测活性成分的靶标。在数据库中找到肝癌相关基因,通过比较筛选出抗肝癌相关基因靶标。使用数据库注释、可视化和综合发现(Database for Annotation, Visualization and Integrated Discovery, DAVID)分析和筛选靶基因和相关通路的功能,并使用 Cytoscape 软件构建茜草抗肝癌作用的成分-靶标-通路网络。最终从茜草中筛选出 16 种活性化合物,涉及 39 个基因靶点,包括 AKT1、丝裂原活化蛋白激酶 1 和表皮生长因子受体。茜草还影响乙型肝炎、磷酸肌醇 3-激酶-蛋白激酶 B 和丝裂原活化蛋白激酶信号通路。许多直接作用的肿瘤相关信号通路和间接作用的肝炎通路抑制肝癌的发生。本研究为进一步阐明茜草抗肝癌的机制提供了科学依据。

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