Advanced Molecular Mechanisms of Baicalein's Neuroprotective Effects in Neurodegenerative Disease Treatments

Baicalein is a flavonoid that demonstrates extensive and significant therapeutic potential for numerous neurodegenerative diseases (NDs). Due to its shared influences on the remediation of NDs, our study adopts a comprehensive approach to illuminate the underlying mechanisms responsible for the effects of baicalein. We initiated our investigation by computationally identifying the potential protein targets of baicalein using SwissTargetPrediction in Homo sapiens. Concurrently, we used the DisGeNET database to identify genes related to NDs. By integrating with baicalein-predicted targets, we build an inclusive network that highlights complex relationships between genes, diseases, and baicalein. Our findings revealed that baicalein predominantly affects the AGE/RAGE pathway, interleukin (notably IL-18 and IL-17), and NF-κB signalings, the pathways associated with inflammation and immune-related functions. Furthermore, the effects of baicalein extend to the pathways with critical roles in NDs, such as BDNF and PI3K-Akt signaling. Using protein-protein interaction networks to validate our findings, we identified key hub proteins (AR, EGFR, SIRT1, MAPK3, APP, ESR1, PTGS2, MMP9, and GSK3B) that may mediate the therapeutic effects of baicalein against NDs. In this case, molecular docking indicates strong binding affinities between them and baicalein. In summary, our detailed study highlights baicalein’s potential as a promising treatment for NDs, offering a molecular basis for its effectiveness.