Epigenetic Modulation Is a Key Mechanism in Cognitive Deficit: Unveiling Garcinol as a Potent HAT Inhibitor in Improving Alzheimer's Disease.

Alzheimer's disease (AD) is a global concern. Conventional FDA-approved drugs mostly provide symptomatic relief but largely fail to address the underlying pathophysiology of AD. Further, chronic use of prescribed anti-AD drugs causes unpredictable, countless side effects, which thus evokes exploration for novel, safer, nontoxic, affordable, yet potent alternative modalities. Among various predicted pathophysiological hall marks in the progression of AD, aberrant histone acetylation has been identified as one of the major culprits, which leads to dysregulated gene expression and gradual neuronal degeneration. Thus, histone acetyl transferase (HAT) inhibitors are considered lucrative anti-AD agents. Active phyto constituents in recent times have occupied the center stage in addressing challenging neurodegenerative disorders in place of routine drug therapy. Garcinol (GL), a phytoactive constituent from Garcinia indica, possesses potent HAT inhibitory effect. Reports show that GL exhibits profound antioxidant, anti-inflammatory, anticancer, and neuroprotection effects. Neuroprotection of GL could be attributed to its ability to reduce oxidative stress and modulate important signaling pathways involved in neuronal degeneration. Present review unveils potentiality of HAT inhibitors in improving memory functions and neuroprotection; with a special focus on GL. Mechanical insights into activity of GL in ameliorating neurodegeneration have been discussed with rationalized evidence of various preclinical reports. Side by side, a portion has been devoted to update the trending drug delivery approaches investigated in recent times for GL toward improved pharmacological performance.