Multi-Target Neuroprotective Effects of Baicalein in Parkinson’s Disease

Abstract

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by dopaminergic neuronal loss. Additionally, mitochondrial dysfunction is one of the key contributors to PD progression. Since Baicalein has neuroprotective potential, this study explores its neuroprotective mechanisms in PD using an integrated in silico approach following in vitro assessment in SH-SY5Y neuronal cells. Methods: PD-related genes were retrieved from DisGeNET and compared with baicalein targets predicted via SwissTargetPrediction, identifying overlapping targets. Protein–protein interaction networks, gene ontology, and KEGG enrichment analyses were performed to determine functional associations. Molecular docking and simulation studies evaluated binding stability with key targets (SIRT3, SOD2, FOXO1, and PPARGC1A). Neuroprotective effects were assessed in MPP⁺-induced SH-SY5Y cells using MTT assay and antioxidant gene expression. Results: Network analysis identified key mitochondrial and oxidative stress–related regulatory hubs. Docking and simulation studies demonstrated stable interactions between baicalein and core targets involved in redox regulation and mitochondrial function. In vitro baicalein treatment significantly improved cell viability in MPP⁺-induced toxicity and restored expression of antioxidant genes, indicating recovery of cellular defense mechanisms. Conclusion: Baicalein may exhibit multi-target neuroprotective activity in PD by modulating integrity and oxidative stress–associated signaling pathways. Convergence of computational and in vitro findings supports its role in restoring neuronal redox balance and enhancing cellular resilience.