Abstract
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 2α, 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.
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The data generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.
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Funding
This research was supported by the National Natural Science Foundation of China (grant number 81300673), Natural Science Foundation of Jiangsu Province (grant number BK20130496), and Startup Foundation for Advanced Talents of Jiangsu University (grant number 13JDG004 & 13JDG006), and Cultivation Project for Young Core Teacher of Jiangsu University.
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All authors contributed to the study conception and design. Specifically, material preparation and data collection were performed by Yang K, Wang J, Liang J, and Yu S. Data analysis was conducted by Zhu A and Zhang R. Wang N and Zhang R co-supervised the work. Wang N wrote the draft of manuscript. Zhang R conceived the original experiment design and edited the paper writing. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Wang, N., Yang, K., Wang, J. et al. Punicalagin relieves lipotoxic injuries on pancreatic β-cells via regulating the oxidative stress and endoplasmic reticulum stress-mediated apoptosis. In Vitro Cell.Dev.Biol.-Animal 59, 575–585 (2023). https://doi.org/10.1007/s11626-023-00806-x
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DOI: https://doi.org/10.1007/s11626-023-00806-x