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基于网络药理学和分子对接预测方法,探讨六味地黄丸治疗耳鸣的潜在作用机制。

Prediction of network pharmacology and molecular docking-based strategy to determine potential pharmacological mechanism of Liuwei Dihuang pill against tinnitus.

机构信息

Jiangxi Hospital of Integrated Traditional Chinese and Western Medicine, Nanchang, Jiangxi, China.

Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi, China.

出版信息

Medicine (Baltimore). 2022 Nov 18;101(46):e31711. doi: 10.1097/MD.0000000000031711.

DOI:10.1097/MD.0000000000031711
PMID:36401375
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9678611/
Abstract

BACKGROUND

Liuwei Dihuang Pill is widely used to treat tinnitus in China. However, the underlying mechanism of Liuwei Dihuang Pill in treating tinnitus still remains unclear.

OBJECTIVE

To explore the potential pharmacological mechanism of Liuwei Dihuang Pill in the treatment of tinnitus based on network pharmacology and molecular docking.

METHODS

The active components of the Liuwei Dihuang Pill were obtained from the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) database. Cytoscape software was used to draw the active component-target network diagram of Liuwei Dihuang Pill, and obtain the core components. Then the corresponding targets were also obtained from the TCMSP database. Targets related to tinnitus were obtained from the GeneCards, DisGeNET, TTD and DrugBank databases. The String database was used to construct protein-protein interaction (PPI) network of common targets of drugs and diseases, then the core targets were screened out. The Annotation, Visualization and Integrated Discovery (DAVID) database was used for gene ontology (GO) enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis of common targets. Finally, the molecular docking between the core component and the core target was carried out by AutoDock.

RESULTS

The core components of Liuwei Dihuang Pill in the treatment of tinnitus including quercetin, stigmasterol, kaempferol, β-sitosterol, tetrahydroalstonine, which may act on core targets such as STAT3, transcription factor AP-1 (JUN), tumor necrosis factor (TNF), interleukin-6 and MAPK3. HIF-1 signaling pathway, Influenza A, P53 signaling pathway, and Toll-like receptor signaling pathway play a role in anti-inflammatory, improving microcirculation in the blood-labyrinth barrier, increasing cochlear blood flow, and preventing hair cell damage. The molecular docking results showed that the affinity between core components and core targets was good.

CONCLUSION

The potential mechanism of Liuwei Dihuang Pill in the treatment of tinnitus was preliminarily discussed in this study, which may provide a theoretical basis and evidence for further experimental research.

摘要

背景

六味地黄丸在中国被广泛用于治疗耳鸣。然而,六味地黄丸治疗耳鸣的潜在机制仍不清楚。

目的

基于网络药理学和分子对接探讨六味地黄丸治疗耳鸣的潜在作用机制。

方法

从中药系统药理学数据库和分析平台(TCMSP)数据库中获取六味地黄丸的活性成分。使用 Cytoscape 软件绘制六味地黄丸的活性成分-靶标网络图,并获得核心成分。然后从 TCMSP 数据库中获得相应的靶标。从 GeneCards、DisGeNET、TTD 和 DrugBank 数据库中获取与耳鸣相关的靶标。使用 String 数据库构建药物-疾病共同靶标的蛋白质-蛋白质相互作用(PPI)网络,然后筛选出核心靶标。使用 DAVID 数据库进行共同靶标的基因本体(GO)富集和京都基因与基因组百科全书(KEGG)通路分析。最后,通过 AutoDock 进行核心成分与核心靶标的分子对接。

结果

六味地黄丸治疗耳鸣的核心成分包括槲皮素、豆甾醇、山奈酚、β-谷甾醇、四氢巴马汀等,可能作用于 STAT3、转录因子 AP-1(JUN)、肿瘤坏死因子(TNF)、白细胞介素-6 和 MAPK3 等核心靶标。HIF-1 信号通路、流感 A、P53 信号通路和 Toll 样受体信号通路在抗炎、改善血迷路屏障中的微循环、增加耳蜗血流和防止毛细胞损伤方面发挥作用。分子对接结果表明核心成分与核心靶标之间的亲和力较好。

结论

本研究初步探讨了六味地黄丸治疗耳鸣的潜在作用机制,可为进一步的实验研究提供理论依据和证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bd6/9678611/675d6824c9f6/medi-101-e31711-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bd6/9678611/2daa3a6e5956/medi-101-e31711-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bd6/9678611/bfcacacd8d5c/medi-101-e31711-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bd6/9678611/2a2e522142e8/medi-101-e31711-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bd6/9678611/ac73afc3941a/medi-101-e31711-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bd6/9678611/730cad5ee4f6/medi-101-e31711-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bd6/9678611/675d6824c9f6/medi-101-e31711-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bd6/9678611/2daa3a6e5956/medi-101-e31711-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bd6/9678611/bfcacacd8d5c/medi-101-e31711-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bd6/9678611/2a2e522142e8/medi-101-e31711-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bd6/9678611/ac73afc3941a/medi-101-e31711-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bd6/9678611/730cad5ee4f6/medi-101-e31711-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bd6/9678611/675d6824c9f6/medi-101-e31711-g006.jpg

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