Veratric Acid as a Potential Antidiabetic Agent: Molecular Docking and In vivo Enzyme Inhibition Studies with Insights from STz-NA Induced Diabetic Rat Model

Streptozotocin-nicotinamide (STz-NA) has proven to be an effective agent in inducing type 2 diabetes (T2DM) in experimental models due to its genotoxic impact on pancreatic β-cells. STz reduces nicotinamide adenine dinucleotide (NAD+) through the glucose transporter GLUT2, leading to cellular damage, DNA strand breaks, and cell death. Nicotinamide (NA), a biochemical precursor of NAD+ and poly-ADP-ribose-polymerase-1 (PARP-1) inhibitor, plays a crucial protective role by modulating NAD+ levels, which are essential in ATP production and other metabolic processes. Excessive DNA damage, however, triggers PARP-1 over-activation, depleting cellular reserves and resulting in cell necrosis.

This study further investigates the antidiabetic and hepatoprotective effects of Veratric Acid (VA) by comparing it to Glibenclamide. Utilizing Computer-Aided Drug Design (CADD), VA was identified as a structurally similar compound with potential antidiabetic properties. Molecular docking studies targeting proteins, such as GLUT-1 (PDB ID: 4PYP) and 1BSI, along with in vivo assays in STz-NA-induced diabetic Wistar rats, were conducted. VA demonstrated significant binding affinity and molecular interactions comparable to standard antidiabetic agents, showing inhibitory effects on liver enzymes SGOT and SGPT, and supporting its potential role in diabetes management.

Docking and histopathology results revealed that VA effectively reduced blood glucose, improved insulin levels, and enhanced liver function in diabetic rats. Additionally, VA promoted insulin secretion from pancreatic β-cells and upregulated insulin-related markers, with minimal hepatotoxicity compared to Glibenclamide. VA treatment significantly improved enzymatic and non-enzymatic antioxidant levels, lowered lipid peroxidation, and improved lipid profiles, which were confirmed by histopathological liver observations.

Veratric Acid at low doses effectively modulates blood glucose and diabetes-related biochemical parameters, highlighting its promise as a safer, natural therapeutic alternative for diabetes treatment.