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<p>Dysregulation of mitochondrial activity is a major cause of diabetes mellitus (DM) and its complications. Astragaloside IV, a natural herbal product, possesses protective properties against DM. This study aimed to evaluate how astragaloside IV affects oxidative stress and mitochondrial function in endothelial progenitor cells (EPCs) and elucidate the underlying mechanisms. A high glucose (HG)-induced human EPC (hEPC) model and a streptozotocin (STZ)-induced DM mouse model were established to investigate the effects of astragaloside IV on EPC function and wound healing in the context of DM. In HG-exposed hEPCs, astragaloside IV reduced apoptosis and increased cell viability and tube formation (<i>P</i> &lt; 0.05). In STZ-induced DM mice, astragaloside IV promoted wound healing and increased the expression of the endothelial marker CD31 (<i>P</i> &lt; 0.05) in wound tissues. In addition, the regulation of oxidative damage and mitochondrial dysfunction by astragaloside IV was investigated. We found that astragaloside IV attenuated mitochondrial damage, decreased ROS and mtROS levels (<i>P</i> &lt; 0.05), decreased MDA activity and enhanced SOD activity (<i>P</i> &lt; 0.05), and downregulated DPR1 levels and upregulated MFN1, MFN2, and OPA1 levels (<i>P</i> &lt; 0.05). Mechanistically, the potential involvement of GSK-3β/Nrf2 was investigated by molecular docking and intervention with the GSK-3β activator sodium nitroprusside (SNP). Astragaloside IV was confirmed to dock with GSK-3β, and it increased the phosphorylation of GSK-3β (<i>P</i> &lt; 0.05) and the expression of Nrf2 as well as its downstream factors HO-1 and NQO1 (<i>P</i> &lt; 0.05). SNP reversed the protective effects of astragaloside IV. These results indicated that astragaloside IV attenuated HG- and STZ-induced injury through the GSK-3β/Nrf2 pathway. These results revealed that astragaloside IV may have the potential to be an active component for protection against DM and its complications.</p>

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Astragaloside IV Relieves Mitochondrial Oxidative Stress Damage and Dysfunction in Diabetic Mice Endothelial Progenitor Cells by Regulating the GSK-3β/Nrf2 Axis

  • 期刊论文

  • 发表日期：

    2025年3月25日

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  • Xiaoling Zou,
  • Xiangnan Liu,
  • Wenjing Qu,
  • Xi Zhang,
  • Yixian Zou,
  • Xiangdong Lin,
  • Wenxiao Hu,
  • Ruchun Gao,
  • Youyuan He,
  • Siyuan Zhou,
  • Yuxuan Huang,
  • Wu Xiong

摘要

Dysregulation of mitochondrial activity is a major cause of diabetes mellitus (DM) and its complications. Astragaloside IV, a natural herbal product, possesses protective properties against DM. This study aimed to evaluate how astragaloside IV affects oxidative stress and mitochondrial function in endothelial progenitor cells (EPCs) and elucidate the underlying mechanisms. A high glucose (HG)-induced human EPC (hEPC) model and a streptozotocin (STZ)-induced DM mouse model were established to investigate the effects of astragaloside IV on EPC function and wound healing in the context of DM. In HG-exposed hEPCs, astragaloside IV reduced apoptosis and increased cell viability and tube formation (P < 0.05). In STZ-induced DM mice, astragaloside IV promoted wound healing and increased the expression of the endothelial marker CD31 (P < 0.05) in wound tissues. In addition, the regulation of oxidative damage and mitochondrial dysfunction by astragaloside IV was investigated. We found that astragaloside IV attenuated mitochondrial damage, decreased ROS and mtROS levels (P < 0.05), decreased MDA activity and enhanced SOD activity (P < 0.05), and downregulated DPR1 levels and upregulated MFN1, MFN2, and OPA1 levels (P < 0.05). Mechanistically, the potential involvement of GSK-3β/Nrf2 was investigated by molecular docking and intervention with the GSK-3β activator sodium nitroprusside (SNP). Astragaloside IV was confirmed to dock with GSK-3β, and it increased the phosphorylation of GSK-3β (P < 0.05) and the expression of Nrf2 as well as its downstream factors HO-1 and NQO1 (P < 0.05). SNP reversed the protective effects of astragaloside IV. These results indicated that astragaloside IV attenuated HG- and STZ-induced injury through the GSK-3β/Nrf2 pathway. These results revealed that astragaloside IV may have the potential to be an active component for protection against DM and its complications.