基于综合网络药理策略研究夏枯草降压作用机制

doi:10.5246/jcps.2024.11.077

中国药学(英文版) ›› 2024, Vol. 33 ›› Issue (11): 1068-1081.DOI: 10.5246/jcps.2024.11.077

基于综合网络药理策略研究夏枯草降压作用机制

孙娜^*(), 王谕靖, 周彩红, 亢欢欢, 马烁, 张玉, 袁宇涵, 张新, 靳琳萱, 李文倩, 吴欣茹, 舒朋华^*()

许昌学院食品与药学院, 河南许昌 461000

收稿日期:2024-04-25 修回日期:2024-05-10 接受日期:2024-07-12 出版日期:2024-12-10 发布日期:2024-12-10
通讯作者: 孙娜, 舒朋华

Exploring the antihypertensive mechanism of Prunella vulgaris through integrated network pharmacology analysis

Na Sun^*(), Yujing Wang, Caihong Zhou, Huanhuan Kang, Shuo Ma, Yu Zhang, Yuhan Yuan, Xin Zhang, Linxuan Jin, Wenqian Li, Xinru Wu, Penghua Shu^*()

Food and Pharmacy College, Xuchang University, Xuchang 461000, Henan, China

Received:2024-04-25 Revised:2024-05-10 Accepted:2024-07-12 Online:2024-12-10 Published:2024-12-10
Contact: Na Sun, Penghua Shu
Supported by:
National Natural Science Foundation of China (Grant No. 21702178), the Training Plan of Young Backbone Teachers in Universities of Henan Province (Grant No. 2021GGJS144), the Key Scientific Research Program in Universities of Henan Province (Grant No. 22A350009 and 23A350012), the National Undergraduate Training Program for Innovation and Entrepreneurship (Grant No. 202410480007 and 202310480020), the Undergraduate Training Program for Innovation and Entrepreneurship of Henan Province (Grant No. 202210480020 and 202210480021), the Scientific Research Innovation Team of Xuchang University (Grant No. 2022CXTD007), the Horizontal Cooperation Project (Grant No. 2023HX181), and the Undergraduate Training Program for Innovation and Entrepreneurship of Xuchang University (Grant No. X202210480016).

摘要/Abstract

摘要：

夏枯草作为一种中药具有显著的降压作用, 尤其对治疗各种类型的高血压有显著疗效。然而, 其降压成分和靶点尚不清楚。本研究旨在探讨夏枯草的降压成分, 并根据降压靶点阐明其作用机制。首先综合利用中药系统药理学数据库与分析平台(TCMSP)、UniProt、GeneCards、STRING、RCSB和人类基因组注释与分析数据库(Metascape)筛选有效成分和降压靶点; 使用网络分析软件Cytoscape 3.9.0筛选活性成分; 使用Sybyl-X 2.0和Discovery Studio 2019进行分子对接。最后使用ADMETlab 2.0在线平台对活性成分的药代动力学和毒性进行预测和分析。8个活性化合物(1–8)和11个降压靶点被筛选, 其中IL1B和PPARG被认为高度相关。可能的生物学过程主要包括细胞凋亡过程的负调控、基因表达的正调控、对外源性刺激的反应和对缺氧的反应。KEGG揭示了核心药理学机制, 如流体剪切应力和动脉粥样硬化、脂质和动脉粥样硬化、P13K-Akt、MAPK和松弛素信号通路。化合物5–8通过氢键、范德华力和π烷基与多个靶标表现出强烈的相互作用, 它们是对接配合物的主要稳定剂。最终, 化合物7具有优异的ADMET预测结果, 可以考虑用于开发药物分子。本研究结果说明夏枯草多靶点、多途径协同治疗高血压, 体现了中药多组分、多靶点作用的特点。

关键词: 夏枯草, 抗高血压, 中药靶点, 天然活性成分

Abstract:

Prunella vulgaris, a traditional Chinese medicine (TCM), exerts a significant hypotensive effect, particularly in managing various forms of hypertension. Nonetheless, the precise antihypertensive constituents and their respective targets remain elusive. This study endeavored to identify the hypotensive components of P. vulgaris and elucidated its mode of action based on hypotensive targets. Utilizing the Systematic Pharmacology of Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), UniProt, GeneCards, STRING, RCSB, and the Human Genome Annotation and Analysis Database (Metascape), we conducted a screening of active ingredients and hypotensive targets. The Network Analyzer software Cytoscape 3.9.0 facilitated a comprehensive analysis of the active ingredients. Molecular docking was executed employing Sybyl-X 2.0 and Discovery Studio 2019. Predictions and analyses of the pharmacokinetics and toxicity of active ingredients were performed using the ADMETlab 2.0 online platform. Eight active compounds (1–8) and 11 hypotensive targets were identified, with IL1B and PPARG exhibiting a high degree of correlation. Dominant biological processes included negative regulation of apoptotic processes, positive regulation of gene expression, response to xenobiotic stimulus, and response to hypoxia. KEGG analysis unveiled core pharmacological mechanisms, notably fluid shear stress and atherosclerosis, lipid and atherosclerosis, P13K-Akt, MAPK, and relaxin signaling pathways. Compounds 5–8 demonstrated robust interactions with multiple targets through hydrogen bonds, van der Waals forces, and pi-alkyl interactions, which serve as primary stabilizers of docking complexes. Notably, compound 7 exhibited promising ADMET prediction results, suggesting its potential for drug molecule development. Our findings underscored the synergistic effects of P. vulgaris on multiple targets and pathways in hypertension treatment, reflecting the characteristic multi-component and multi-target effects of TCM.

Key words: Prunella vulgaris L., Anti-hypertension, Traditional Chinese medicine targets, Natural active ingredients

Supporting: /attached/file/20241208/20241208163838_778.pdf

孙娜, 王谕靖, 周彩红, 亢欢欢, 马烁, 张玉, 袁宇涵, 张新, 靳琳萱, 李文倩, 吴欣茹, 舒朋华. 基于综合网络药理策略研究夏枯草降压作用机制[J]. 中国药学(英文版), 2024, 33(11): 1068-1081.

Na Sun, Yujing Wang, Caihong Zhou, Huanhuan Kang, Shuo Ma, Yu Zhang, Yuhan Yuan, Xin Zhang, Linxuan Jin, Wenqian Li, Xinru Wu, Penghua Shu. Exploring the antihypertensive mechanism of Prunella vulgaris through integrated network pharmacology analysis[J]. Journal of Chinese Pharmaceutical Sciences, 2024, 33(11): 1068-1081.

图/表 13

Figure 1. Active compounds screened from P. vulgaris.

Table 1. The compounds screened out in the Traditional Chinese Medicines Database.

Figure 2. Venn diagram of P. vulgaris and hypertension.

Figure 3. Interaction network between active compounds and antihypertensive targets.

Figure 4. PPI network (left) and key target proteins interaction network (right).

Figure 5. GO terms of 104 potential targets. The top 10 GO functional terms were selected (P ≤ 0.05). Note: The color of terms turned from blue to red. The redder the bar was, the smaller the adjusted P value was. Abbreviations: BP: biological processes; CC: cellular component; MF: molecular function.

Figure 6. KEGG pathway enrichment of 104 potential targets. The top 20 pathways were identified. Color represented the P value, and the size of the spot represented the count of genes.

Table 2. The data of the top 20 KEGG pathways.

Figure 7. The histograms of relative scoring percentages for compounds docking with ILB1 (A) and PPARG (B), respectively.

Figure 8. Docking and binding pattern of compound 5 (pink) into TP53 active site (lift) and 2D interaction diagram of compound 5 (pink) with amino acid residues of TP53 (right).

Figure 9. Docking and binding pattern of compound 8 (yellow) into IL6 active site 2D interaction diagram of compound 8 (yellow) with amino acid residues of IL6.

Table 3. ADMET prediction results of compounds 1–8.

Figure 10. Possible toxic groups of compounds 1–8.

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基于综合网络药理策略研究夏枯草降压作用机制

Exploring the antihypertensive mechanism of Prunella vulgaris through integrated network pharmacology analysis

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