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

Abstract 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.