In-silico evaluation of neuroprotective action of phytoestrogen molecules on estrogen alpha receptors

Neurodegenerative diseases, like Alzheimer’s disease (AD) and Parkinson’s disease (PD), are defined by progressive neuronal damage driven by oxidative stress, neuroinflammation, and protein misfolding. Phytoestrogens, such as isoflavones (daidzein, genistein) and lignans (enterolactone, enterodiol), have surfaced as potential neuroprotective agents because of their antioxidant, anti-inflammatory, and estrogen receptor alpha (ERα)-modulating properties. This study utilized computational tools to examine the binding affinities, pharmacokinetics, and toxicity profiles of these compounds. Molecular docking exposed strong interactions between isoflavones/lignans and ERα, with genistein exhibiting the highest binding affinity (−8.6 kcal/mol). SwissADME analysis showed favorable gastrointestinal absorption and blood-brain barrier permeability, notably for enterolactone. Toxicity assessments utilizing GUSAR predicted low acute toxicity, backing their safety profile. The results suggest that these phytoestrogens, especially genistein and enterolactone, can act as multi-target neuroprotective agents by modulating ERα-mediated pathways. Further experimental validation is required to translate these findings into clinical applications for neurodegenerative diseases.