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Background <p>Diabetic nephropathy (DN) is a severe complication of diabetes that may lead to end-stage renal disease (ESRD). Arbutin (ARB), a naturally occurring glycoside with known therapeutic properties, has shown potential benefits for diabetes. This study explored the efficacy of ARB in modulating DN through its influence on Nrf2/HO-1 signaling, along with its ability to suppress inflammation and oxidative stress.</p> Methods <p>Streptozotocin (STZ) injection was used to induce diabetes, and ARB was administered orally for 8 weeks.</p> Results <p>The results revealed that ARB effectively alleviated hyperglycemia and attenuated weight loss and renal hypertrophy and damage. ARB significantly attenuated kidney oxidative stress, reduced pro-inflammatory markers, and inhibited apoptosis, as evidenced by decreased levels of MDA, NO, NF-κB p65, IL-1β, TNF-α, Bax, and caspase-3, and myeloperoxidase activity. These improvements were associated with upregulated Nrf2, HO-1 and NQO-1, enhanced antioxidant defenses, inhibition of Keap1, and upregulation of Bcl-2. Molecular docking studies further corroborated the binding affinity of ARB to NF-κB p65, caspase-3, iNOS, Keap1, and HO-1.</p> Conclusion <p>ARB mitigates DN progression by reducing hyperglycemia, inflammation, and oxidative stress while strengthening antioxidant and signaling mechanisms involving Nrf2/HO-1 pathway.</p> Graphical Abstract <p></p>

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Protective Effect of Arbutin Against Diabetic Nephropathy: Targeting Oxidative Stress, Inflammation, and Nrf2/HO-1 Pathway

  • 期刊论文

  • 发表日期：

    2026年3月12日

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  • Reem S. Alruhaimi,
  • Sulaiman M. Alnasser,
  • Ali F. Almutairy,
  • Mohammed F. Alotaibi,
  • Emad H. M. Hassanein,
  • Ayman M. Mahmoud

摘要

Background

Diabetic nephropathy (DN) is a severe complication of diabetes that may lead to end-stage renal disease (ESRD). Arbutin (ARB), a naturally occurring glycoside with known therapeutic properties, has shown potential benefits for diabetes. This study explored the efficacy of ARB in modulating DN through its influence on Nrf2/HO-1 signaling, along with its ability to suppress inflammation and oxidative stress.

Methods

Streptozotocin (STZ) injection was used to induce diabetes, and ARB was administered orally for 8 weeks.

Results

The results revealed that ARB effectively alleviated hyperglycemia and attenuated weight loss and renal hypertrophy and damage. ARB significantly attenuated kidney oxidative stress, reduced pro-inflammatory markers, and inhibited apoptosis, as evidenced by decreased levels of MDA, NO, NF-κB p65, IL-1β, TNF-α, Bax, and caspase-3, and myeloperoxidase activity. These improvements were associated with upregulated Nrf2, HO-1 and NQO-1, enhanced antioxidant defenses, inhibition of Keap1, and upregulation of Bcl-2. Molecular docking studies further corroborated the binding affinity of ARB to NF-κB p65, caspase-3, iNOS, Keap1, and HO-1.

Conclusion

ARB mitigates DN progression by reducing hyperglycemia, inflammation, and oxidative stress while strengthening antioxidant and signaling mechanisms involving Nrf2/HO-1 pathway.

Graphical Abstract