Exploring the Active Compounds of Traditional Mongolian Medicine Baolier Capsule (BLEC) in Patients with Coronary Artery Disease (CAD) Based on Network Pharmacology Analysis, Molecular Docking and Experimental Validation

Abstract

Objective: Baolier Capsule (BLEC) is a Traditional Mongolian Medicine comprising fifteen herbs. This study aims to illustrate the synergistic mechanism of BLEC in the treatment of Coronary Artery Disease (CAD) by using network pharmacology method, molecular docking and experimental validation. Methods: Searching and screening the active ingredients of different herbs in BLEC and target genes related to CAD in multiple databases. Subsequently, Protein–Protein Interactions Network (PPI-Net), gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment were used to identify the key targets. AutoDock was used to verify the binding ability between the active ingredient and key target through molecular docking. Reverse Transcription-Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR) was used to verify the effect of active ingredient of BLEC on the key target gene. Finally, effect of BLEC on the degree of blood lipids and atherosclerosis was validated by animal experiment. Results: There are 144 active components and 80 CAD-related targets that are identified in BLEC in the treatment of CAD. What is more, 8 core genes were obtained by clustering and topological analysis of PPI-Net. Further, GO and KEGG analysis showed that fluid shear stress and atherosclerosis are the key pathways for BLEC to treat CAD. These results were validated by molecular docking method. In vitro, active compounds of BLEC (Quercetin, luteolin, kaempferol, naringenin, tanshinone IIA, β-carotene, 7-O-methylisomucronulatol, piperine, isorhamnetin and Xyloidone) can inhibit 8 core gene (AKT1, EGFR, FOS, MAPK1, MAPK14, STAT3, TP53 and VEGFA) expression. Moreover, BLEC not only improve blood lipid levels but also inhibit the development of atherosclerosis in ApoE-knockout mice. Conclusion: Our research first revealed the basic pharmacological effects and related mechanisms of in the treatment of CAD. The predicted results provide some theoretical support for BLEC or its important active ingredients to treat CAD.