Explore the mechanism of Citri Reticulatae Pericarpium (Chenpi) in atherosclerosis Based on Network Pharmacology, Molecular Docking and Experimental Evidence

Abstract

Background: Citri Reticulatae Pericarpium (CRP), a traditional Chinese medicine, is extensively used to prevent and treat cardiovascular diseases. However, the exact target and pharmacological mechanism of CRP remain unclear. This study aims to investigate the potential mechanism of CRP in treating atherosclerosis (AS) using network pharmacology, molecular docking, and experimental verification. Methods: The chemical constituents and targets of CRP were retrieved, collected, and screened in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) database. Potential AS targets were obtained from GeneCards and OMIM databases. Subsequently, the STRING database was used to establish a protein-protein interaction network, and Cytoscape was employed to construct the CRP-AS-potential target gene network to identify core targets. After GO and KEGG enrichment analysis, naringenin and core targets were selected for molecular docking simulation. Finally, the anti-AS mechanism of naringenin was validated through cell experiments. Results: Five potential active components of CRP were identified, and 54 common targets of the disease and drugs, including 15 core targets (such as MAPK3 and MMP9), were obtained. Lipid and atherosclerosis were found to be the most prominent pathways of action. Molecular docking demonstrated the strong binding of naringenin with MMP9 and MAPK3. In vitro experiments, it was revealed that naringenin might inhibit lipid accumulation in smooth muscle cells and slow down the occurrence of atherosclerosis by decreasing the expression of MAPK3. Conclusions: Through network pharmacological analysis, molecular docking, and experimental verification, this study found that naringenin, the core active ingredient of CRP, may inhibit the occurrence of smooth muscle cell foam by reducing the expression of MAKP3 in vascular smooth muscle cells (VSMCs)and play an anti-AS role, providing a new idea for further research on CRP and naringenin in the prevention and treatment of AS.