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整合网络药理学与RT-qPCR分析以探究泽泻汤介导治疗非酒精性脂肪性肝病的潜在机制

Integrating Network Pharmacology and RT-qPCR Analysis to Investigate the Mechanisms Underlying ZeXie Decoction-Mediated Treatment of Non-alcoholic Fatty Liver Disease.

作者信息

Wu Jiashuo, Zhang Fangqing, Ruan Haonan, Chang Xiaoyan, Wang Jingxun, Li Zhuangzhuang, Jin Weiyi, Shi Yue

机构信息

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

College of Public Health, Hebei Medical University, Shijiazhuang, China.

出版信息

Front Pharmacol. 2021 Sep 9;12:722016. doi: 10.3389/fphar.2021.722016. eCollection 2021.

DOI:10.3389/fphar.2021.722016
PMID:34566646
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8458890/
Abstract

ZeXie Decoction (ZXD) is a traditional Chinese medicine composed of (Sam.) Juzep. and Koidz. ZXD has been widely used to treat non-alcoholic fatty liver disease (NAFLD). The mechanistic basis for the pharmacological activity of ZXD, however, remains poorly understood. In this study, we used a network pharmacology approach and investigated the association between ZXD and NAFLD. We identified the active ingredients of ZXD and screened the potential targets of these ingredients, after which a database of relevant NAFLD-related targets were constructed and several enrichment analyses were performed. Furthermore, the ethanol and aqueous extracts of ZXD were prepared and experimental pharmacology validation was conducted using RT-qPCR of the non-alcoholic fatty liver disease (NAFLD) model in Sprague-Dawley (SD) rats. As a result, a herb-compound-target-pathway network model was developed, and HMGCR, SREBP-2, MAPK1, and NF-Bp65 targets were validated. The gene expression results of these four targets were consistent with those of the network pharmacology prediction. Using an integration strategy, we revealed that ZXD could treat NAFLD by targeting HMGCR, SREBP-2, MAPK1, and NF-Bp65.

摘要

泽泻汤（ZXD）是一种由泽泻（Sam.）Juzep.和 科伊茨（Koidz.）组成的中药。泽泻汤已被广泛用于治疗非酒精性脂肪性肝病（NAFLD）。然而，泽泻汤药理活性的作用机制仍知之甚少。在本研究中，我们采用网络药理学方法，研究了泽泻汤与非酒精性脂肪性肝病之间的关联。我们确定了泽泻汤的活性成分，并筛选了这些成分的潜在靶点，之后构建了相关的非酒精性脂肪性肝病相关靶点数据库，并进行了多项富集分析。此外，制备了泽泻汤的乙醇提取物和水提取物，并使用实时定量聚合酶链反应（RT-qPCR）对Sprague-Dawley（SD）大鼠的非酒精性脂肪性肝病（NAFLD）模型进行了实验药理学验证。结果，建立了一个草药-化合物-靶点-通路网络模型，并验证了3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）、固醇调节元件结合蛋白2（SREBP-2）、丝裂原活化蛋白激酶1（MAPK1）和核因子κB p65（NF-κBp65）靶点。这四个靶点的基因表达结果与网络药理学预测结果一致。通过整合策略，我们揭示了泽泻汤可以通过靶向HMGCR、SREBP-2、MAPK1和NF-κBp65来治疗非酒精性脂肪性肝病。

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