Integrative bioinformatics and molecular docking unveil multi-target therapeutic mechanisms of Coptidis Rhizoma (CR) against Lewy body dementia (LBD): an in-silico approach

Abstract

Background: Lewy body dementia (LBD) is a complex neurodegenerative disorder characterized by the presence of Lewy bodies in the brain, leading to cognitive decline and motor symptoms. The exploration of potential therapeutic mechanisms is crucial for developing effective treatments. Coptidis Rhizoma (CR) has been traditionally used in herbal medicine, and its compounds may offer novel therapeutic avenues for LBD. Materials and Methods: In this study, an integrative bioinformatics approach was employed to investigate the molecular interactions between CR compounds and LBD-associated targets. The authors collected relevant targets from the OMIM and NCBI databases and utilized bioinformatics tools for protein-protein interaction (PPI) network analysis, gene ontology, and KEGG pathway enrichment. Molecular docking simulations were conducted using PyRx software to evaluate binding interactions between CR compounds and key proteins associated with LBD.

Results: The analysis revealed 20 critical hub genes, including MAPT, GBA, SNCA, TARDBP, and PRKN, which play significant roles in neurodegeneration. Key processes involved in LBD, such as neuronal apoptosis regulation, oxidative stress response, and synaptic transmission, were identified. The molecular docking results indicated compelling interactions, with Obacunone exhibiting a binding energy of -9.4 kcal/mol for GBA and -9.2 kcal/mol for PRKN, suggesting its strong affinity for these targets. Similarly, Coptisine demonstrated high binding potential with GBA (-9.4 kcal/mol), while Worenine showed notable interaction with SNCA (-7.4 kcal/mol), reinforcing their therapeutic relevance.

Conclusion: This computational study provides valuable insights into the therapeutic mechanisms of CR compounds for LBD. The findings underscore the importance of experimental validation to confirm the predicted interactions and therapeutic potential, paving the way for future in vitro and in vivo investigations to address this challenging neurodegenerative disorder.

Keyword: Lewy body dementia (LBD), Coptidis Rhizoma (CR), neurodegenerative disorder, network pharmacology, molecular docking