Nootropic Property of Punica grantum Extract as BDNF4 Stimulant for Treatment of Major Depressive Disorder

In 2008, the World Health Organization (WHO) stressed major depressive disorder (MDD) as the third most important cause of disease burden worldwide. Based on their projections, it is expected that by 2030, MDD will take the lead among the rest of the world’s health concerns. Brain derived neurotrophic factor 4 (BDNF4), a protein of neurotrophins family play pivotal role in maintaining neural plasticity, and its reduced level in the hippocampus and plasma have been reported in patients with MDD. Nootropic drugs serve as therapeutic interventions in mitigating MDD through diverse molecular mechanisms. Punica granatum (pomegranate) is acknowledged for its nutritional and medicinal properties, currently under medical scrutiny for its potential as a natural antidepressant. Various computational methodologies, including molecular docking, pharmacokinetics, ADME (absorption, distribution, metabolism and excretion) profile assessment, toxicological analysis, and prediction of biological activity, were employed to identify promising compounds among the phytochemicals present in Punica extract, focusing on their potential BDNF4-stimulating, nootropic, and antidepressant properties. The comprehensive examination of docking scores, interactions between proteins and ligands, pharmacological and toxicological attributes, along with the forecasting of biological activities, collectively underscores the potential attributes of M-Cymene, Flavylium, 2-(4-Methylphenyl)propan-2-ol, Thymol, and Pelletierine as prospective drug candidates targeting human BDNF4 for alleviating MDD.