Punicalagin relieves lipotoxic injuries on pancreatic β-cells via regulating the oxidative stress and endoplasmic reticulum stress-mediated apoptosis

Cellular toxicity of hyperlipidemia has been long considered a major cause of various intractable disease such as diabetes. Discovering lipotoxicity antagonist with high efficiency and low side effects is of importance to develop therapeutics for relevant diseases. In the current study, we evaluate the anti-lipotoxic potential of punicalagin (PU) on pancreatic cells and investigate its underpinning mechanism involved. The administration of PU effectively improved cell viability, quenched intracellular reactive oxygen species, alleviated lipid peroxidation, and enhanced cellular antioxidative capacity in RINm5F cells stimulated by sodium palmitate. Besides that, PU treatment significantly inhibited the overload of mitochondrial calcium ions; alleviated the activation of endoplasmic reticulum (ER) stress mediators including glucose-regulated protein 78, protein kinase RNA-like ER kinase, eukaryotic initiation factor 2 alpha, activating transcription factor 6, caspase 12, and C/EBP homologous protein (CHOP); and attenuated the expression of cleaved caspase 3 and poly ADP-ribose polymerase in test cells. Further RNA interference experiment results and miR211-5p expression analysis revealed that PU may directly mitigate CHOP expression and upregulate the expression of miR211-5p to reduce ER stress-induced pancreatic cell death. The efficacy of PU in maintaining redox equilibrium and diminishing ER stress on pancreatic cells stressed by hyperlipidemia suggests that PU can be used as a promising dietary natural product to safeguard the pancreatic health against lipotoxicity.

Automated summary

In this study, the potential of punicalagin (PU) in protecting pancreatic cells against lipotoxicity was evaluated. PU effectively improved cell viability, maintained redox equilibrium, and diminished endoplasmic reticulum (ER) stress in cells stimulated by high lipid levels. It was found that PU may directly mitigate CHOP expression and upregulate the expression of miR211-5p to reduce ER stress-induced pancreatic cell death.