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<p>Pancreatic β cells that produce insulin play a significant role in maintaining glucose homeostasis. However, high glucose (HG) causes oxidative stress, which leads to pancreatic β cell dysfunction. The synthesis of lipoic acid (LA) and plumbagin (PLU) conjugate (LA-PLU) was done and characterized using (1H) NMR, (13C) NMR, LC–ESI–MS/MS, and UV–visible spectroscopy techniques. ADME analysis confirmed the drug-like properties of LA-PLU. The present study revealed the protective effect of LA-PLU conjugate against HG (25&#xa0;mM)-induced oxidative stress on pancreatic β cells. Cell viability was performed on RIN-5F cells and found that LA-PLU exhibits non-toxic up to 91.23 ± 2.61% of cell viability at 12.5&#xa0;µM concentration. At 12.5&#xa0;µM, LA-PLU protected pancreatic β cells up to 73.45 ± 3.72% under HG conditions. LA-PLU showed a protective effect on RIN-5F cells against HG-induced DNA damage, followed by preserving mitochondrial membrane potential and decreasing reactive oxygen species formation. Further, LA-PLU showed an anti-apoptotic effect by increasing the Bcl-2 (B cell lymphoma-2) level and decreasing the apoptotic proteins [Bcl-2 associated x (Bax), and cleaved caspase-3). Hence, the overall study concludes that LA-PLU could act as a potent antioxidant that protects the RIN-5F cells under HG conditions, resulting in the maintenance of glucose homeostasis.</p>

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Lipoic acid-plumbagin conjugate protects pancreatic beta cells against high glucose-induced toxicity

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月1日

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  • Parveen Abdulhaniff,
  • Chitra Loganathan,
  • Penislusshiyan Sakayanathan,
  • Palvannan Thayumanavan

摘要

Pancreatic β cells that produce insulin play a significant role in maintaining glucose homeostasis. However, high glucose (HG) causes oxidative stress, which leads to pancreatic β cell dysfunction. The synthesis of lipoic acid (LA) and plumbagin (PLU) conjugate (LA-PLU) was done and characterized using (1H) NMR, (13C) NMR, LC–ESI–MS/MS, and UV–visible spectroscopy techniques. ADME analysis confirmed the drug-like properties of LA-PLU. The present study revealed the protective effect of LA-PLU conjugate against HG (25 mM)-induced oxidative stress on pancreatic β cells. Cell viability was performed on RIN-5F cells and found that LA-PLU exhibits non-toxic up to 91.23 ± 2.61% of cell viability at 12.5 µM concentration. At 12.5 µM, LA-PLU protected pancreatic β cells up to 73.45 ± 3.72% under HG conditions. LA-PLU showed a protective effect on RIN-5F cells against HG-induced DNA damage, followed by preserving mitochondrial membrane potential and decreasing reactive oxygen species formation. Further, LA-PLU showed an anti-apoptotic effect by increasing the Bcl-2 (B cell lymphoma-2) level and decreasing the apoptotic proteins [Bcl-2 associated x (Bax), and cleaved caspase-3). Hence, the overall study concludes that LA-PLU could act as a potent antioxidant that protects the RIN-5F cells under HG conditions, resulting in the maintenance of glucose homeostasis.