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网络药理学解析银莱汤治疗肺炎的作用机制。

Network pharmacology to dissect the mechanisms of Yinlai Decoction for pneumonia.

机构信息

Department of Acupuncture and Mini-invasive Oncology, Beijing University of Chinese Medicine Third Affiliated Hospital, Beijing, 100029, People's Republic of China.

School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 100029, People's Republic of China.

出版信息

BMC Complement Med Ther. 2020 Jun 3;20(1):168. doi: 10.1186/s12906-020-02954-z.

Abstract

BACKGROUND

Pneumonia is a common respiratory disorder, which brings an enormous financial burden to the medical system. However, the current treatment options for pneumonia are limited because of drug resistance and side effects. Our previous study preliminarily confirmed that Yinlai Decoction (YD), a common prescription for pneumonia in clinical practice, can regulate the expression of inflammatory factors, but the mechanisms are unknown yet.

METHODS

In our work, a method named network pharmacology was applied, which investigated the underlying mechanisms of herbs based on a variety of databases. We obtained bioactive ingredients of YD on TCMSP database and collected potential targets of these ingredients by target fishing. Then the pneumonia-related targets database was built by TTD, Drugbank, HPO, OMIM, and CTD. Based on the matching targets between YD and pneumonia, the PPI network was built by STRING to analyze the interactions among these targets and then input into Cytoscape for further topological analysis. DAVID and KEGG were utilized for GO and pathway enrichment analysis. Then rat model based on LPS stimulated pneumonia was used to verify the possible mechanism of YD in treating pneumonia.

RESULTS

Sixty-eight active ingredients, 103 potential targets and 8 related pathways, which likely exert a number of effects, were identified. Three networks were constructed using Cytoscape, which were herb-component-network, YD-pneumonia target network, and herb-component-YD target-pneumonia network. YD was verified to treat LPS-induced pneumonia by regulating the inflammatory factor IL-6, which was a predicted target.

CONCLUSION

Network analysis indicated that YD could alleviate the symptoms and signs of pneumonia through regulating host immune inflammatory response, angiogenesis and vascular permeability, the barrier function of the airway epithelial cells, hormone releasing and cell growth, proliferation, and apoptosis.

摘要

背景

肺炎是一种常见的呼吸系统疾病,给医疗系统带来了巨大的经济负担。然而,由于耐药性和副作用,目前肺炎的治疗选择有限。我们之前的研究初步证实,临床实践中治疗肺炎的常用方剂银莱汤(YD)可以调节炎症因子的表达,但机制尚不清楚。

方法

在我们的工作中,应用了一种名为网络药理学的方法,该方法基于各种数据库研究草药的潜在机制。我们从 TCMSP 数据库中获得了 YD 的生物活性成分,并通过靶标捕捞收集了这些成分的潜在靶标。然后,通过 TTD、Drugbank、HPO、OMIM 和 CTD 构建了肺炎相关靶标数据库。基于 YD 与肺炎的匹配靶标,通过 STRING 构建 PPI 网络,分析这些靶标之间的相互作用,然后输入 Cytoscape 进行进一步的拓扑分析。使用 DAVID 和 KEGG 进行 GO 和通路富集分析。然后,利用 LPS 刺激的肺炎大鼠模型验证 YD 治疗肺炎的可能机制。

结果

鉴定出 68 种活性成分、103 个潜在靶标和 8 个相关通路,可能发挥多种作用。使用 Cytoscape 构建了三个网络,分别是草药-成分网络、YD-肺炎靶标网络和草药-成分-YD 靶标-肺炎网络。通过调节预测靶标 IL-6,YD 被验证可用于治疗 LPS 诱导的肺炎。

结论

网络分析表明,YD 通过调节宿主免疫炎症反应、血管生成和血管通透性、气道上皮细胞的屏障功能、激素释放和细胞生长、增殖和凋亡,缓解肺炎的症状和体征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0a23/7268734/61d39652d972/12906_2020_2954_Fig1_HTML.jpg

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