Pongamol as a multitarget neuroprotective candidate: an integrative analysis of in silico predictions and biological evidence

Pongamol, a bioactive flavonoid derived from Pongamia pinnata (Fabaceae), has gained attention as a potential therapeutic agent for neurological disorders. Neurodegenerative and neuropsychiatric conditions such as Alzheimer’s, Parkinson’s, epilepsy, anxiety and depression are driven by oxidative stress, neuroinflammation, mitochondrial dysfunction, apoptosis and neurotransmitter imbalance, while current treatments remain largely symptomatic. This study evaluates the neuroprotective potential of pongamol using integrated in silico and experimental approaches. SwissADME analysis revealed favourable pharmacokinetic properties, including good oral bioavailability, high gastrointestinal absorption, blood–brain barrier permeability and non-substrate behaviour for P-glycoprotein. Prediction of activity spectra of substances predictions indicated antioxidant, anti-inflammatory, anti-Alzheimer’s, antiparkinsonian, GABAergic, nootropic and cytoprotective activities. Target mapping identified interactions with potassium channels, melatonin receptors, phosphodiesterase-4D and kynurenine pathway enzymes. These findings were further supported by limited experimental studies suggesting possible attenuation of oxidative stress, suppression of neuroinflammation, inhibition of apoptosis and improvement in cognitive and behavioural outcomes in disease models, highlighting pongamol as a promising multitarget neuroprotective candidate.