Imagine embarking on a thrilling adventure, exploring the vast and intricate network of a bustling city. Just as the city relies on a complex web of interconnected streets, buildings, and transportation routes to function, our bodies are also made up of a network of molecular interactions. In the realm of Alzheimer’s disease (AD), a powerful herbal remedy called Coptidis Rhizoma (CR) has emerged as a potential ally in the battle against cognitive decline. More than just a single road to healing, CR operates at multiple levels and mechanisms to combat AD. Using cutting-edge network pharmacology techniques, researchers have delved deep into the world of CR to unravel its pharmacologic mysteries. They have discovered that CR contains numerous active compounds that target specific molecules involved in AD pathology, providing hope for new treatment strategies. By constructing interactive networks and analyzing these intricate connections, scientists have identified crucial targets within the network that hold promise for therapeutic intervention. Additionally, they have explored the biological processes and signaling pathways influenced by CR, shedding light on its antioxidative and pro-apoptotic effects. This groundbreaking research not only uncovers the mechanisms underlying CR’s efficacy but also hones in on potential clinical applications. The study signals an exciting new era in AD research, fostering optimism for finding effective treatments for neurodegenerative diseases. Dive into the fascinating details of this study to gain a deeper understanding of how CR tackles Alzheimer’s and explore the possibilities it holds for future therapeutic development.

BackgroundAlzheimer’s disease (AD) is becoming a more prevalent public health issue in today’s culture. The experimental study of Coptidis Rhizoma (CR) and its chemical components in AD treatment has been widely reported, but the principle of multi-level and multi-mechanism treatment of AD urgently needs to be clarified.ObjectiveThis study focuses on network pharmacology to clarify the mechanism of CR’s multi-target impact on Alzheimer’s disease.MethodsThe Phytochemical-compounds of CR have been accessed from the Traditional Chinese Medicine Database and Analysis Platform (TCMSP) and Symmap database or HPLC determination. The values of Oral Bioavailability (OB) ≥ 30% and Drug Like (DL) ≥ 0.18 or blood ingredient were used to screen the active components of CR; the interactive network of targets and compounds were constructed by STRING and Cytoscape platform, and the network was analyzed by Molecular Complex Detection (MCODE); Gene Ontology (GO) function, Kyoto Encyclopedia of Genes and Genomes Pathway (KEGG) and metabolic pathway enrichment of targets were carried out with Metascape, the Database for Annotation, Visualization and Integrated Discovery (DAVID) and MetaboAnalyst platform; Based on CytoHubba, the potential efficient targets were screened by Maximal Clique Centrality (MCC) and Degree, the correlation between potential efficient targets and amyloid β-protein (Aβ), Tau pathology was analyzed by Alzdata database, and the genes related to aging were analyzed by Aging Altas database, and finally, the core targets were obtained; the binding ability between ingredients and core targets evaluated by molecular docking, and the clinical significance of core targets was assessed with Gene Expression Omnibus (GEO) database.Results19 active components correspond to 267 therapeutic targets for AD, of which 69 is potentially effective; in module analysis, RELA, TRAF2, STAT3, and so on are the critical targets of each module; among the six core targets, RELA, MAPK8, STAT3, and TGFB1 have clinical therapeutic significance; GO function, including 3050 biological processes (BP), 257 molecular functions (MF), 184 cellular components (CC), whose functions are mainly related to antioxidation, regulation of apoptosis and cell composition; the HIF-1 signaling pathway, glutathione metabolism is the most significant result of 134 KEGG signal pathways and four metabolic pathways, respectively; most of the active components have an excellent affinity in docking with critical targets.ConclusionThe pharmacological target prediction of CR based on molecular network pharmacology paves the way for a multi-level networking strategy. The study of CR in AD treatment shows a bright prospect for curing neurodegenerative diseases.

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