Nicotinamide-cinnamic acid cocktail exerts pancreatic β-cells survival coupled with insulin secretion through ERK1/2 signaling pathway in an animal model of apoptosis.

Purpose: Pancreatic β-cells protection is integral to insulin secretion in diabetic conditions. In this context, we investigated cinnamic acid in combination with nicotinamide on the regulation of insulin secretion and apoptosis in pancreatic β-cells using streptozotocin (STZ)-induced apoptotic model in vivo.

Methods: The pancreata of nicotinamide (NA)-cinnamic acid (CA) treated rats were studied using histopathological, immunofluorescence, molecular docking, and RT-PCR analyses, supported by serum glucose and insulin levels.

Results: The biochemical data revealed that the acute treatment of NA and CA in combination significantly increased serum insulin, thereby lowering blood glucose level in vivo. From histological findings, NA-CA pre-treatment displayed significant protection against STZ-apoptotic trends, improved insulin secretion, and recapitulated the STZ-induced morphology to normal control. The upregulated expressions of caspases, caused by STZ-treatments, were significantly downregulated with NA-CA in immunofluorescent detection and their translational levels, respectively. We found dense ERK½-insulin staining and p-ERK½ expression, which was further supported by strong ERK½ residues-ligands interactions based on in silico analysis.

Conclusion: From the pre-clinical data, we thus conclude that NA-CA cocktail exerts dual insulin releasing and survival effects in pancreatic β-cells by targeting ERK½ pathway.