Systematic Pharmacology and GEO Database Mining Revealed the Therapeutic Mechanism of Xuefu Zhuyu Decoration for Atherosclerosis Cardiovascular Disease

Abstract

Background: Xuefu Zhuyu decoration (XFZYD), as a traditional Chinese compound recipe, has been used to treat atherosclerosis cardiovascular disease (ASCVD) for thousands of years in China, but its effective compounds and underlying treatment molecular mechanism remains promiscuous, which severely limits its clinical application.Methods: The effective components and their targets of XFZYD were predicted and screened based on the Traditional Chinese Medicine System Pharmacology (TCMSP) database. The candidate therapeutic targets of ASCVD were screened by Pharmacogenomics Knowledgebase (PharmGKB) and Comparative Toxicogenomics Database (CTD). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses for target proteins were performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Differentially expressed genes were identified using the GEO2R online tool. Molecular docking was performed by Schrodinger software. To assess the efficacy of the prediction, human umbilical vein endothelial cells (HUVECs) treated with the effective compound of XFZYD were used as the in vitro model.Results: A total of 108 effective compounds (including quercetin) and 137 candidate therapeutic targets were identified. Analyzing the relationships among effective compounds, candidate therapeutic targets, and signaling pathways, the therapy mechanisms of XFZYD were mainly reflected in the protection of vascular endothelium, anti-inflammatory, antioxidant stress, etc. Accordingly, we found the effective compound of XFZYD (quercetin) decreased intracellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) expressions and pro-inflammatory cytokines in HUVECs treated with lipopolysaccharide (LPS), and reduced the adhesion function of HUVECs with monocytes. The inhibitor of the predicted target protein (PTGS2) could further reduce the expressions of VCAM-1, ICAM-1, and TNF-α induced by LPS, and inhibit the adhesion function of HUVECs with monocytes, while PTGS2 agonists partially counteracted the protective effect of quercetin.Conclusions: In this study, the effective components and potential therapeutic targets of XFZYD for ASCVD treatment were explored from the perspective of systemic pharmacology. The effective component quercetin was verified to protect endothelial cells by reducing endothelial inflammatory response and impeding the attachment of monocytes against the predicted therapeutic target PTGS2.

The Improvement of Cardiac and Endothelial Functions of Xue-Fu-Zhu-Yu Decoction for Patients with Acute Coronary Syndrome: A Meta-Analysis of Randomized Controlled Trials

“…Therefore, additional research studies are required in the future. The systemic pharmacology of XFZYD in the prevention of atherosclerotic cardiovascular disease (ASCVD) has shown that the mechanism of XFZYD is mainly reflected in the protection of vascular endothelium, prevention of oxidative stress, and inhibition of inflammation; the effective component quercetin was also shown to protect injured endothelial cells and reduce the endothelial inflammatory response (ICAM-1, VCAM-1, and TNF- α ) induced by LPS in vitro [ 47 ]. XFZYD has been shown to protect from ischemic necrosis, induce the migration of endothelial progenitor cells, and promote angiogenesis by improving the serum levels of NO [ 48 ].…”

Anti-atherosclerotic effects of naringenin and quercetin from Folium Artemisiae argyi by attenuating Interleukin-1 beta (IL-1β)/ matrix metalloproteinase 9 (MMP9): network pharmacology-based analysis and validation

“…Candidate target genes were identified in the GEO database (GSE9128, GSE71226), including total RNA expression data from coronary heart disease in human. GEO2R was used to identify the differentially expressed genes (DEGs), p ≤ 0.05, and |log FC| > 1 were the screening limitations [ 21 ].…”

The Potential of Bioactive Fish Collagen Oligopeptides against Hydrogen Peroxide-Induced NIH/3T3 and HUVEC Damage: The Involvement of the Mitochondria

“…To support and extend the findings of previous in vivo research on mice, we selected mouse embryonic fibroblasts NIH/3T3, which are commonly employed in the cell senescence and oxidative stress model [23,24], to evaluate the protective effect of FCOPs on oxidative stress-induced damaged cells and its possible biological mechanism. Considering that the role of antioxidants may vary in different species and different tissues, we once more selected HUVECs, which are frequently utilized in the model of CVDs, since endothelial dysfunction caused by various factors, including oxidative stress, is the initiating factor of CVDs [25,26]. Given that CVDs are the most fatal chronic non-communicable illness, research into the protective role of FCOPs against oxidatively damaged HUVECs is crucial.…”