System biology-based assessment of the molecular mechanism of epigallocatechin gallate in Parkinson’s disease: via network pharmacology, in-silico evaluation & in-vitro studies

Abstract

Abstract Epigallocatechin gallate (EGCG) compound (IMPHY000226) has the potential to modulate multiple molecular mechanisms involved in Parkinson’s disease. Multiple targets such as SIRT3, FOXO1, PRKAA1, PPARGC1A, and CREBBP directly regulate reactive oxygen species levels and oxidative stress, suggesting that targeting these genes could help prevent further cellular damage. EGCG targets were identified using Swiss target prediction, revealing 31 targets modulated by EGCG. Specific keywords were used to identify 4663 targets related to PD modulation. The network was constructed and analyzed using the node and edge counts. Clustering analysis identified specific target groups with high edge counts and Kappa scores, indicating potential key players in PD modulation. The targets SIRT3, FOXO1, and PPARGC1A were predicted to have the highest binding energies via dual algorithm-based molecular docking studies. The MD simulation studies were performed for the highest-docked targets, SIRT3, FOXO1, and PPARGC1A, to assess the stability and interactions. The cell viability assays were conducted at various dosage concentrations for EGCG and resveratrol, which provided dose-dependent effects on cell survival. In the toxicity-induced group, the highest % cell viability of 94% and 81% was observed at a dosage of 6.25 µg/mL and 12.5 µg/mL. The toxicity-induced gene expression studies indicated that the EGCG upregulated the targets SOD2, FOXO1, and GPx. EGCG and resveratrol upregulated the targets SOD2, FOXO1, and GPx at a dosage concentration of 12.5 µg/mL. EGCG was found to be more potent than the resveratrol molecule, indicating that EGCG can be used as an anti-Parkinson agent.

Keywords

• SIRT3
• FOXO1
• Parkinson’s disease
• Oxidative stress
• Network pharmacology