Naturally-occurring carboxylic acids from traditional antidiabetic plants as potential pancreatic islet FABP3...

The antidiabetic action of traditional plants is mostly attributed to their antioxidant and anti-inflammatory properties. These plants are still having some secrets, making them an attractive source that allows for investigating new drugs or uncovering precise pharmacologic antidiabetic functions of their constituents. In diabetes, which is a lipid disease, long-term exposure of pancreatic islet beta cells to fatty acids (FAs) increases basal insulin release, reduces glucose-stimulated insulin secretion, causes islet beta cell inflammation, failure and apoptosis. Pancreatic islet beta cells express fatty acid binding protein 3 (FABP3) that receives long-chain FAs and traffics them throughout different cellular compartments to be metabolized and render their effects. Inhibition of this FABP3 may retard FA metabolism and protect islet beta cells. Since FAs interact with FABPs by their carboxylic group, some traditionally-known antidiabetic plants were reviewed in the present study, searching for their components that have common features of FABP ligands, namely carboxylic group and hydrophobic tail. Many of these carboxylic acids were computationally introduced into the ligand-binding pocket of FABP3 and some of them exhibited FABP3 ligand possibilities. Among others, the naturally occurring ferulic, cleomaldeic, caffeic, sinapic, hydroxycinnamic, 4-p-coumaroylquinic, quinoline-2-carboxylic, chlorogenic, 6-hydroxykynurenic, and rosmarinic acids in many plants are promising candidates for being FABP3-specific inhibitors. The study shed light on repurposing these phyto-carboxylic acids to function as FABP inhibitors. However, more in-depth biological and pharmacological studies to broaden the understanding of this function are needed.