Key ingredients in Verbena officinalis and determination of their anti-atherosclerotic effect using a computer-aided drug design approach

Frontiers in Plant Science

Plant Science

Jingxuan Yu¹  Yuanyuan Gan²  Yuting Chen²  Xiao Ye²  Wei Yu³ 

[1] Clinical Medical College, Changsha Medical University, Changsha, Hunan, China;School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei, China;School of Pharmacy, Xianning Medical College, Hubei University of Science and Technology, Xianning, Hubei, China;Hubei Engineering Research Center of Traditional Chinese Medicine of South Hubei Province, Xianning, Hubei, China;

关键词: Verbena officinalis;    atherosclerosis (AS);    network pharmacology approach;    molecular docking;    molecular dynamics simulation;   

DOI  :  10.3389/fpls.2023.1154266

 received in 2023-01-30, accepted in 2023-03-16,  发布年份 2023

来源: Frontiers

【 摘 要 】

Lipid metabolism disorders may considerably contribute to the formation and development of atherosclerosis (AS). Traditional Chinese medicine has received considerable attention in recent years owing to its ability to treat lipid metabolism disorders using multiple components and targets. Verbena officinalis (VO), a Chinese herbal medicine, exhibits anti-inflammatory, analgesic, immunomodulatory, and neuroprotective effects. Evidence suggests that VO regulates lipid metabolism; however, its role in AS remains unclear. In the present study, an integrated network pharmacology approach, molecular docking, and molecular dynamics simulation (MDS) were applied to examine the mechanism of VO against AS. Analysis revealed 209 potential targets for the 11 main ingredients in VO. Further, 2698 mechanistic targets for AS were identified, including 147 intersection targets between VO and AS. Quercetin, luteolin, and kaempferol were considered key ingredients for the treatment of AS based on a potential ingredient target–AS target network. GO analysis revealed that biological processes were primarily associated with responses to xenobiotic stimuli, cellular responses to lipids, and responses to hormones. Cell components were predominantly focused on the membrane microdomain, membrane raft, and caveola nucleus. Molecular functions were mainly focused on DNA-binding transcription factor binding, RNA polymerase II-specific DNA-binding transcription factor binding, and transcription factor binding. KEGG pathway enrichment analysis identified pathways in cancer, fluid shear stress, and atherosclerosis, with lipid and atherosclerosis being the most significantly enriched pathways. Molecular docking revealed that three key ingredients in VO (i.e., quercetin, luteolin, and kaempferol) strongly interacted with three potential targets (i.e., AKT1, IL-6, and TNF-α). Further, MDS revealed that quercetin had a stronger binding affinity for AKT1. These findings suggest that VO has beneficial effects on AS via these potential targets that are closely related to the lipid and atherosclerosis pathways. Our study utilized a new computer-aided drug design to identify key ingredients, potential targets, various biological processes, and multiple pathways associated with the clinical roles of VO in AS, which provides a comprehensive and systemic pharmacological explanation for the anti-atherosclerotic activity of VO.

【 授权许可】

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Copyright © 2023 Chen, Gan, Yu, Ye and Yu