Computational Discovery of the Neuroprotective Potential of Karanjin Against Parkinson's Disease

Parkinson's disease, a degenerative neurological disorder, characterized by dopaminergic neuron loss, oxidative stress, and α-synuclein aggregation. Current therapies face limitations like side effects and lack of disease-modifying potential. This study investigates karanjin, a Furano flavonoid from Pongamia pinnata, as a putative multi-target neuroprotective agent using in silico approaches. ADME and toxicity profiling (SwissADME, ProTox-II) revealed karanjin's drug-likeness, blood-brain barrier permeability, and low hepatotoxicity. Network pharmacology identified SRC kinase, PI3K-Akt, and MAPK signalling as key targets, with karanjin modulating oxidative stress and neuroinflammation pathways. Molecular docking (Glide XP) demonstrated strong binding affinity (−100.1 kcal/mol) of karanjin to SRC kinase (PDB: 8HQA), stabilized by hydrogen bonds (Ser345, Gln275) and hydrophobic interactions (Tyr340, Leu393). Molecular dynamics simulations (100 ns) confirmed complex stability (RMSD < 2.5 Å), with consistent residue interactions (>70% occupancy). These results highlight karanjin's potential as a multi-target, BBB-penetrant neuroprotective activity.