Elucidate the Neuro-Pharmacodynamic Actions of 3-Hydroxypterostilbene

Abstract

Pterostilbene (dimethyl ether analog of resveratrol) is a metabolically stable natural bioactive and has exhibited substantial pharmacological activities. 3-Hydroxypterostilbene is a natural pterostilbene analog and an active metabolite of Pterostilbene. The current literature reveals antimicrobial (anti-fungal), anti-obesity, and anti-cancer (skin, leukemia, and colon) activities. However, there are no reports on the actions of 3-Hydroxypterostilbene on the central nervous system. Consequently, there is a void in the neuropharmacological effect of 3-Hydroxypterostilbene. Therefore, this study investigated the pharmacodynamic effect of 3-Hydroxypterostilbene on the dopaminergic and hippocampal neurons. Additionally, in-silico analyses were performed to validate its neuro-pharmacodynamic effects. The in-silico studies revealed its ability to cross the blood-brain barrier and in-vitro studies established the ability to significantly inhibit the dopaminergic and hippocampal neuronal viability. 3-Hydroxypterostilbene induced significant neurotoxicity (hippocampal and dopaminergic neuronal death) by enhancing apoptosis (Caspase-3 activity) and by inhibiting tyrosine hydroxylase activity without inducing oxidative stress and mitochondrial dysfunction.