Exploring the protective mechanism of baicalin in treatment of atherosclerosis using endothelial cells degranulation model and network pharmacology

Abstract Background: Baicalin is widely used in clinical practice. The present study aimed to assess the underlying mechanism of baicalin in treatment of atherosclerosis (AS) with the help of network pharmacology, molecular docking and experimental validation. Materials and methods: The target genes of baicalin and AS were identified from public databases, and the overlapping results were considered to be baicalin-AS targets. Core target genes of baicalin were obtained through the PPI network and clinical data sets GSE132651. Human aortic endothelial cells (HAECs) were treated with baicalin, followed by Lipopolysaccharide (LPS) to construct a model of endothelial injury. The expression of core targets was examined by real-time qPCR. Flow cytometry was used to detect reactive oxygen species (ROS) level. Results: NOX4 is likely to be the core target of baicalin for AS, and its expression was inhibited in AS patients compared to controls. Functional enrichment analysis demonstrated that most targets were involved in oxidative stress. Intervention with baicalin increased the expression levels of NOX4 and NOS3 (eNOS). Moreover, baicalin also blocked the LPS-induced ROS generation in HAECs. Conclusions: Baicalin might ameliorate oxidative stress on endothelial cells via targeting NOX4.