Exploring resveratrol against Alzheimer's disease and Parkinson's disease through integrating network pharmacology, bioinformatics, and experimental validation strategy in vitro

Background: The study aims to investigate the pharmacological basis and molecular mechanisms of resveratrol in the treatment of Alzheimer's disease (AD) and Parkinson's disease (PD) through the approach of treating different diseases with the same method, guided by traditional Chinese medicine theory. Utilizing network pharmacology and bioinformatics methods, this research aims to provide modern medical evidence for the theory of treating different diseases with the same method in traditional Chinese medicine. Methods: Omnibus from Swiss Target Prediction, TCMSP, SuperPred, SEA, HIT, CTD, TCMIP and Gene Expression Disease datasets for resveratrol related genes, Alzheimer's disease, and Parkinson's disease were obtained from the GEO database. Core targets were identified by weighted gene coexpression network analysis (WGCNA) and minimum absolute contraction and selection operator (LASSO). The expression of core targets was verified in AD and PD cell models. The immune characteristics of AD and PD were analyzed by CIBERSORT algorithm. Finally, the potential mechanism of resveratrol intervention on the core target was studied by molecular docking technique. Results: The results of network pharmacological analysis showed that resveratrol acted on 85 common targets such as STAT3 and CASP3, affected AGE-RAGE signaling pathway and PI3K-Akt signaling pathway, and showed the effect of "same disease and different treatment" for AD and PD. Three core targets associated with AD and PD (PLK4, FCGRT, and PRKAR2A) were finally identified through comprehensive transcriptome analysis, and experimentally verified in cell models of AD and PD. At the same time, the analysis of immune cell infiltration suggested that AD and PD had dysregulation of inflammation, and the core target was significantly related to M2 macrophages. Conclusion: Resveratrol may play a potential mechanism of "treating the same disease with different diseases" and target three core targets (PLK4, FCGRT and PRKAR2A) to improve the disease process of AD and PD by participating in the regulation of immune and inflammatory pathways. These findings have potential implications for clinical practice and future research.