A Systems Pharmacology Approach, Using Molecular Docking and Dynamics Simulation, to Unlock Potential New Therapies for Alzheimer’s Disease: A Case Study of Cinnamon Species

Author(s): Wen Qiu1, Shouli Yuan, Robbie Kelleher, Lina Sun, Wei Chen, Helen Sheridan, Junying Liu, Weiguang Lv

Cinnamon (Cinnamomum spp.) is a time-honored species that has been used as a medicine, spice, and flavoring agent for millennia. Some forms of cinnamon are useful in treating neurological disorders including Alzheimer's disease (AD). However, the mechanisms of action are unclear. To elucidate the potential therapeutic value of mechanism, cinnamon ingredients and targets were determined by searching diverse herb databases. AD targets were searched on GeneCards and filtered by reprocessing scRNA-Seq data, which were filtered by STRING to construct the Herb-Ingredient-Target-Disease network. The intersection with AD targets (3445) gave a cinnamon - AD common target set (321). Metascape analysis revealed an enriched pathway/GO process and 123 genes enriched in the Alzheimer’s disease pathway were targeted for 78 cinnamon phytochemical components. Effective compounds including eugenol, cinnamaldehyde and coumarin, mainly function against hub targets, for which the binding was validated through molecular docking and dynamics simulation, e.g., cinnamaldehyde against ACHE, PTGS2. Data gathered here suggests that cinnamon may promote anti- Aß aggregation and clearance and modulate the calcium signaling pathway. It provides a therapeutic basis for (hybrid) drug development of cinnamon extracts. Ultimately this study contributes to understanding the mechanism of action of cinnamon constituent metabolites in the treatment of AD.