Hidden pharmacological activities of valproic acid: A new insight

Abstract

Valproic acid (VPA) is an approved drug for managing epileptic seizures, bipolar disorders, and migraine. VPA has been shown to elevate the level of gamma-aminobutyric acid (GABA) in the brain through competitive inhibition of GABA transaminase, thus promoting the availability of synaptic GABA and facilitating GABA-mediated responses. VPA, which is a small chain of fatty acids, prevents histone deacetylases (HDACs). HDACs play a crucial role in chromatin remodeling and gene expression through posttranslational changes of chromatin-associated histones. Recent studies reported a possible effect of VPA against particular types of cancers. This effect was partially attributed to its role in regulating epigenetic modifications through the inhibition of HDACs, which affect the expression of genes associated with cell cycle control, cellular differentiation, and apoptosis. In this review, we summarize the current information on the actions of VPA in diseases such as diabetes mellitus, kidney disorders, neurodegenerative diseases, muscular dystrophy, and cardiovascular disorders.