Potential targets and mechanisms of Guarana in the treatment of Alzheimer's disease based on network pharmacology

• Main Authors: J.I.A.O. Zhilin (Author), G.A.O. Xuemei (Author)
• Format: Book
• Published: KeAi Communications Co., Ltd., 2023-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 2589-3777; 10.1016/j.dcmed.2023.02.005
• Keywords: [Key words] Guarana (Paullinia cupana); Alzheimer's disease; network pharmacology; β-Amyloid; molecular docking; Medicine; R; Other systems of medicine; RZ201-999
• Source: Digital Chinese Medicine, Vol 6, Iss 1, Pp 55-66 (2023)

Objective: To dig the main active components and predict potential mechanisms of Guarana in the treatment of Alzheimer's disease (AD) by network pharmacology method and molecular docking. Methods: By digging into papers relating to this topic, chemical components in Guarana were obtained and used for drug-likeness analysis. Databases including HERB and Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) were used to obtain potential targets that the active components in Guarana might have effects on, and to find out diseases in association with the potential targets. Other databases such as GeneCards, a human gene database, and DisGeNET were used to identify the genes relating to AD, and a Wayne diagram was drawn to get the intersected targets in Guarana and AD. Subsequently, CytoScape software was adopted for the construction of a Guarana-intersected targets-AD map. After that, the intersected targets were uploaded to the Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) database to acquire a protein-protein interaction (PPI) network diagram. Then, the key target proteins were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). In terms of molecular docking verification, AutoDock software was used to verify whether the crucial active compounds of Guarana's components could bind to the key targets. Results: A total of 140 potential targets for Guarana to treat AD were obtained. The results of PPI network analysis showed that interleukin 6 (IL-6), tumor necrosis factor (TNF), insulin (INS), mitogen-activated protein kinase 3 (MAPK3), transcription factor (JUN), cell tumor antigen p53 (TP53), caspase3 (CASP3), protein c-Fos (FOS), catalase (CAT), and Catenin beta-1 (CTNNB1) might be the key targets of Guarana in the treatment of AD. It was found by GO and KEGG analyses that the mechanism of Guarana in the treatment of AD might be the bindings between Guarana compounds and protease outside the cell membranes. The molecular docking results showed that the small molecules of various components in Guarana binding to target proteins such as TNF, IL-6, MAPK3, and FOS needed relatively less energy. Conclusion: The treatment of AD with Guarana involves the participation of multiple targets, among which IL-6, TNF, and MAPK3 might be the key ones. These key targets might take effects through the biological process in their bindings to β-amyloid and involving signaling pathways in cancer. Hopefully, our research could offer some scientific foundations as well as references for in-depth studies on the treatment of AD with Guarana.