基于网络药理学和分子对接探讨陈皮治疗阿尔茨海默病的作用机制

doi:10.5246/jcps.2024.02.012

中国药学(英文版) ›› 2024, Vol. 33 ›› Issue (2): 142-155.DOI: 10.5246/jcps.2024.02.012

基于网络药理学和分子对接探讨陈皮治疗阿尔茨海默病的作用机制

陈云丽¹^,², 颜仁梁³, 李丽莎², 张亚敏², 徐小妹², 卢雪花², 徐榕青², 林文津¹^,²^,^*()

^1. 福建中医药大学药学院, 福建福州 350122
^2. 福建省医学测试重点实验室, 福建省医学科学研究院, 福建福州 350001
^3. 广东食品药品职业学院, 广东广州 510000

收稿日期:2023-07-21 修回日期:2023-08-26 接受日期:2023-09-23 出版日期:2024-03-03 发布日期:2024-03-03
通讯作者: 林文津

Mechanism of Citri Reticulatae Pericarpium in treating Alzheimer’s disease based on network pharmacology and molecular docking

Yunli Chen¹^,², Renliang Yan³, Lisha Li², Yamin Zhang², Xiaomei Xu², Xuehua Lu², Rongqing Xu², Wenjin Lin¹^,²^,^*()

¹ College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, Fujian, China
² Fujian Key Laboratory of Medical Analysis, Fujian Academy of Medical Sciences, Fuzhou 350001, Fujian, China
³ Guangdong Food and Drug Vocational College, Guangzhou 510000, Guangdong, China

Received:2023-07-21 Revised:2023-08-26 Accepted:2023-09-23 Online:2024-03-03 Published:2024-03-03
Contact: Wenjin Lin
Supported by:
Guangdong Provincial Medical Research Fund Project (Grant No. A2023416), Academic level project of Guangdong Food and Drug Vocational College (Grant No. 2022ZR04, 2023ZR03).

摘要/Abstract

摘要：

本研究通过网络药理学和分子对接阐明陈皮(Citri Reticulatae Pericarpium, CRP)治疗阿尔茨海默病(Alzheimer’s disease, AD)的作用机制。首先, 在陈皮中筛选出98个有靶点的化合物和628个相关成分靶点, 在疾病数据库中检索得到2483个AD靶点。随后, 构建CRP-AD交叠靶点图和蛋白互作(PPI)网络图, 对PPI网络图进行拓扑属性分析得到66个与CRP治疗AD密切相关的靶点, 对66个靶点进行GO功能和KEGG通路富集分析, 靶点在多条生物途径富集, 包括松弛素信号通路、钙信号通路、HIF-1信号通路和IL-17信号通路。最后, 对靶点和CRP活性成分进行分子对接验证, CRP的活性成分(黄烷酮、橘皮素、‎黄酮醇‎、香芹酚、紫苏醛)与靶点通过氢键连接, 结合能小于0 kg/mol。本研究采用网络药理学和分子对接的方法系统的揭示了陈皮治疗阿尔茨海默病的作用机制, 为以后科研以及临床研究提供理论依据。

关键词: 陈皮, 阿尔茨海默病, 网络药理学, 分子对接

Abstract:

The objective of this study was to elucidate the mechanism by which Citri Reticulatae Pericarpium (CRP) treated Alzheimer’s disease (AD) using network pharmacology and molecular docking. Initially, a screening process identified 98 target compounds and 628 related component targets within CRP. Additionally, 2483 AD targets were retrieved from disease databases. Subsequently, an overlapping targets map was constructed, integrating CRP and AD targets, followed by the creation of a protein-protein interaction network map to identify 66 targets closely associated with the treatment of AD using CRP. These targets were identified through topological attribute analysis. To gain further insights, GO function and KEGG pathway enrichment analyses were conducted on the 66 identified targets. The results revealed enrichment in various biological pathways, including the relaxin signaling pathway, calcium signaling pathway, HIF-1 signaling pathway, and IL-17 signaling pathway. Finally, molecular docking verification was performed on the targets and active components of CRP. Active components, such as flavanone, tangeretin, flavonol, carvacrol, and perillaldehyde, were found to form hydrogen bonds with targets, with binding energies below 0 kg/mol. This study utilized network pharmacology and molecular docking methods to systematically elucidate the mechanism by which CRP treats AD. The findings provided a theoretical foundation for future research and clinical investigations.

Key words: Citri Reticulatae Pericarpium, Alzheimer's disease, Network pharmacology, Molecular docking

Supporting: /attached/file/20240308/20240308224252_40.pdf

陈云丽, 颜仁梁, 李丽莎, 张亚敏, 徐小妹, 卢雪花, 徐榕青, 林文津. 基于网络药理学和分子对接探讨陈皮治疗阿尔茨海默病的作用机制[J]. 中国药学(英文版), 2024, 33(2): 142-155.

Yunli Chen, Renliang Yan, Lisha Li, Yamin Zhang, Xiaomei Xu, Xuehua Lu, Rongqing Xu, Wenjin Lin. Mechanism of Citri Reticulatae Pericarpium in treating Alzheimer’s disease based on network pharmacology and molecular docking[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(2): 142-155.

图/表 10

Figure 1. Study flowchart.

Figure 2. Venn diagram of CRP-AD.

Figure 3. PPI network diagram of the target proteins.

Table 1. Top 20 key targets information.

Figure 4. The key targets degree values and PPI network.

Figure 5. GO functional enrichment analysis.

Figure 6. KEGG pathway enrichment analysis.

Table 2. The binding energy of molecular docking between key targets and corresponding active components of CRP.

Table 3. Active components and structure of CRP.

Figure 7. Molecular docking results.

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基于网络药理学和分子对接探讨陈皮治疗阿尔茨海默病的作用机制

Mechanism of Citri Reticulatae Pericarpium in treating Alzheimer’s disease based on network pharmacology and molecular docking

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