Neurological potency of native plants from sub-Himalayan West Bengal through reverse pharmacology

Abstract

Neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and epilepsy, pose a growing global health challenge due to an aging population. These conditions share common processes, including protein accumulation, oxidative stress, and neuro-inflammation, making their treatment complex and costly. Network pharmacology, an innovative approach integrating systems biology and computational biology, offers insights into multi-target formulations and the repurposing of existing medications for neurodegenerative diseases. We shortlisted 730 bioactive compounds from 25 traditional Himalayan plants, assessed their drug-like properties using ADME criteria, and predicted their potential target proteins through reverse docking and pharmacophore mapping. Our study identified 287 compounds with high gastrointestinal absorption and good blood-brain barrier permeability. These compounds were subjected to target prediction, yielding a list of 171 potential target proteins. Functional annotation and pathway enrichment analysis highlighted their involvement in steroid hormone-related pathways, MAPK signaling, FOXO signaling, TNF signaling, VEGF signaling, and neurotrophin signaling. Importantly, one plant, Valeriana jatamansi, exhibited an association with beta-amyloid binding activity, a potential therapeutic approach for AD. From our study we could understand how these plants modulate our body to manage these diseases. However, further in vitro and in vivo validation is needed before commercial and public use of this data.