Network Pharmacology and Molecular Docking Analysis of the Mechanisms of Combined Radix Bupleuri (Chai-Hu) and Radix Paeoniae Alba (Bai-Shao) Treatment in the Prevention and Treatment of Alzheimer’s Disease

Abstract Objective: Radix Bupleuri and Radix Paeoniae Alba are referred to as Chai-Hu and Bai-Shao, respectively, in Chinese. We used molecular docking and network pharmacological approaches to explore the active components of this Chinese herb combination which is commonly used for treating Alzheimer’s disease (AD), the Chai-Hu and Bai-Shao pair (CBP). Materials and Methods: The active compounds and action targets of Chai-Hu and Bai-Shao were identified in the Traditional Chinese Medicine Systems Pharmacology database, and the Therapeutic Target Database, DrugBank, GenCards, DisGeNET, and Online Mendelian Inheritance in Man databases were used to identify therapeutic targets in patients with AD. To identify a common target of CBP in the treatment of AD, we used the Metascape tool to perform Gene Ontology function enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. In addition, CBP-AD protein–protein interaction (PPI) and herb-component-target networks were created using Cytoscape 3.8.2. Molecular docking was verified using AutoDock tools. Results: We identified 20 active compounds of CBP, 202 active targets, 1,323 disease targets, and 117 active compound disease intersection targets; the PPI network showed that the top eight key targets were AKT1, interleukin (IL) 6, JUN, MAPK1, tumor necrosis factor, TP53, vascular endothelial growth factor, and epidermal growth factor. These act mainly on the fluid shear stress, atherosclerosis, IL-17, hypoxia-inducible factor-1, and nonalcoholic fatty liver disease pathways, among others, which control immune inflammation, cell proliferation, and apoptosis. Based on molecular docking results, the active components of CBP bind well to its key targets. Conclusion: Our results indicated that CBP was effective for treating AD by reducing the expression of inflammatory factors, promoting cell proliferation and differentiation, and preventing nerve cell death and anti-neuronal cell apoptosis.