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基于网络药理学的预测益金汤对高脂血症和动脉粥样硬化作用的活性化合物和分子靶标。

Network pharmacology-based prediction of active compounds and molecular targets in Yijin-Tang acting on hyperlipidaemia and atherosclerosis.

机构信息

Herbal Medicine Research Division, Korea Institute of Oriental Medicine, 1672 Yuseong-daero, Yuseong-gu, Daejeon 34054, Republic of Korea.

Bioinformatics Group, R&D Center, Insilicogen Corporation, 35, Techno 9-ro, 34027, Republic of Korea.

出版信息

J Ethnopharmacol. 2018 Jul 15;221:151-159. doi: 10.1016/j.jep.2018.04.027. Epub 2018 Apr 23.

DOI:10.1016/j.jep.2018.04.027
PMID:29698773
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Yijin-Tang (YJT) is a traditional prescription for the treatment of hyperlipidaemia, atherosclerosis and other ailments related to dampness phlegm, a typical pathological symptom of abnormal body fluid metabolism in Traditional Korean Medicine. However, a holistic network pharmacology approach to understanding the therapeutic mechanisms underlying hyperlipidaemia and atherosclerosis has not been pursued.

AIM OF THE STUDY

To examine the network pharmacological potential effects of YJT on hyperlipidaemia and atherosclerosis, we analysed components, performed target prediction and network analysis, and investigated interacting pathways using a network pharmacology approach.

MATERIALS AND METHODS

Information on compounds in herbal medicines was obtained from public databases, and oral bioavailability and drug-likeness was screened using absorption, distribution, metabolism, and excretion (ADME) criteria. Correlations between compounds and genes were linked using the STITCH database, and genes related to hyperlipidaemia and atherosclerosis were gathered using the GeneCards database. Human genes were identified and subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.

RESULTS

Network analysis identified 447 compounds in five herbal medicines that were subjected to ADME screening, and 21 compounds and 57 genes formed the main pathways linked to hyperlipidaemia and atherosclerosis. Among them, 10 compounds (naringenin, nobiletin, hesperidin, galangin, glycyrrhizin, homogentisic acid, stigmasterol, 6-gingerol, quercetin and glabridin) were linked to more than four genes, and are bioactive compounds and key chemicals. Core genes in this network were CASP3, CYP1A1, CYP1A2, MMP2 and MMP9. The compound-target gene network revealed close interactions between multiple components and multiple targets, and facilitates a better understanding of the potential therapeutic effects of YJT.

CONCLUSIONS

Pharmacological network analysis can help to explain the potential effects of YJT for treating dampness phlegm-related diseases such as hyperlipidaemia and atherosclerosis.

摘要

民族药理学相关性

益津汤(YJT)是一种传统的治疗高脂血症、动脉粥样硬化等病症的方剂,这些病症与异常体液代谢的传统韩国医学中的湿痰有关。然而,目前还没有采用整体网络药理学方法来理解高脂血症和动脉粥样硬化的治疗机制。

研究目的

为了研究 YJT 对高脂血症和动脉粥样硬化的网络药理学潜在作用,我们采用网络药理学方法分析成分,进行靶点预测和网络分析,并研究相互作用途径。

材料和方法

从公共数据库中获取草药中的化合物信息,并使用吸收、分布、代谢和排泄(ADME)标准筛选口服生物利用度和药物相似性。使用 STITCH 数据库将化合物与基因相关联,并使用 GeneCards 数据库收集与高脂血症和动脉粥样硬化相关的基因。识别人类基因并进行京都基因与基因组百科全书(KEGG)通路分析。

结果

网络分析确定了五种草药中的 447 种化合物,这些化合物经过 ADME 筛选,有 21 种化合物和 57 种基因形成了与高脂血症和动脉粥样硬化相关的主要途径。其中,10 种化合物(柚皮苷、川陈皮素、橙皮苷、高良姜素、甘草酸、对羟基苯乙酸、豆甾醇、6-姜辣素、槲皮素和甘草素)与超过 4 种基因相关联,是生物活性化合物和关键化学物质。该网络中的核心基因是 CASP3、CYP1A1、CYP1A2、MMP2 和 MMP9。化合物-靶点基因网络揭示了多种成分和多个靶点之间的密切相互作用,有助于更好地理解 YJT 的潜在治疗效果。

结论

药理学网络分析可以帮助解释 YJT 治疗高脂血症和动脉粥样硬化等与湿痰相关疾病的潜在作用。

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