In Silico Elucidation of Molecular Mechanisms of Luteolin and Gramine against Parkinson’s Disease

Abstract

Parkinson's disease (PD) is a progressive neurodegenerative condition that causes dopaminergic neuronal loss, oxidative stress, mitochondrial dysfunction, neuroinflammation, and α-synuclein aggregation. Natural phytochemicals have received attention because of their multitarget neuroprotective properties. The current study sought to assess the therapeutic mechanisms of Luteolin and Gramine against Parkinson's disease utilizing integrated network pharmacology and molecular docking methods. Potential Luteolin and Gramine targets were identified using SwissTargetPrediction and PubChem, respectively, whereas PD-associated genes were identified using GeneCards. STRING and Cytoscape were used to assess common targets, which were then enriched for Gene Ontology (GO) and KEGG pathways. Major targets found by network pharmacology include PIK3R1, PTK2, AKT1, EGFR, AKR1C3, IGF1R, CDK1, and CYP19A1, which are linked to oxidative stress, neuroinflammation, apoptosis, and neuronal survival. The dopaminergic synapse signaling pathway played a substantial role, according to KEGG analysis. Luteolin binds better to PIK3R1 (PDB: 6D85; -7.4 kcal/mol) and PTK2 (PDB: 4NY0; -7.6 kcal/mol) than Levodopa and Gramine, according to molecular docking analysis. The data imply that luteolin and gramine have neuroprotective effects in Parkinson's disease via modulating many targets and pathways.