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

Abstract

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.

Exploring the Potential Mechanisms of Guanxinshutong Capsules in Treating Pathological Cardiac Hypertrophy based on Network Pharmacology, Computer-Aided Drug Design, and Animal Experiments

“…Using the Metascape server for GO and KEGG enrichment analysis, we identified a series of closely related biological processes, cellular components, and molecular functions, as well as essential signaling pathways involved in GXST treatment of PCH. To better understand these processes and pathways, we uploaded the top 20 terms to the Bioinformatics platform for visualization analysis . Next, through the analysis of the PPI network, GO enrichment analysis, and KEGG pathways, we identified the core proteins involved in the GXST treatment of PCH.…”

“…To better understand these processes and pathways, we uploaded the top 20 terms to the Bioinformatics platform for visualization analysis. 34 Next, through the analysis of the PPI network, GO enrichment analysis, and KEGG pathways, we identified the core proteins involved in the GXST treatment of PCH.…”

Exploring the mechanism of Jinlida granules against type 2 diabetes mellitus by an integrative pharmacology strategy

“…Based on the molecular docking results, AKT-Luteolin, TNF-Quercetin, IL-6-Quercetin, TP53-Luteolin, PTGS2-Quercetin, STAT3-Baicalein and CASP3-Baicalein had the best binding performance for each key target. The molecular dynamics simulation of AKT1-Luteolin, TNF-Quercetin-, IL-6-Quercetin, TP53-Luteolin and PTGS2-Quercetin have been performed by others [23][24][25][26] . In our study, STAT3-Baicalein and CASP3-Baicalein were subjected to molecular dynamics simulation analyses for 100 ns.…”