Revealing rutaecarpine's promise: A pathway to parkinson's disease relief through PPAR modulation

Int Immunopharmacol. 2025 Jan 13:147:114076. doi: 10.1016/j.intimp.2025.114076. Online ahead of print.

Abstract

The pathological mechanisms of Parkinson's disease (PD) is complex, and no definitive cure currently exists. This study identified Rutaecarpine (Rut), an alkaloid extracted from natural plants, as a potential therapeutic agent for PD. To elucidate its mechanisms of action and specific effects in PD, network pharmacology, molecular docking, and experimental validation methods were employed. Our findings demonstrated the efficacy of Rut in ameliorating PD symptoms. Network pharmacology analysis indicated that Rut exerts its therapeutic effects through the PPAR signaling pathway and the lipid pathway. Molecular docking results revealed that Rut forms stable protein-ligand complexes with PPARα and PPARγ. Animal experiments showed that Rut improved motor function in PD mice, protected dopaminergic neurons, ameliorated lipid metabolism disorders, and reduced neuroinflammation. This study identified the critical molecular mechanisms and therapeutic targets of Rut in the treatment of PD, providing a theoretical foundation for future investigations into the pharmacodynamics of Rut as a potential anti-PD agent.

Keywords: Molecular docking; Network pharmacology; Parkinson’s disease; Rutaecarpine.