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

Abstract

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. Streptozotocin (STZ) injection was used to induce diabetes, and ARB was administered orally for 8 weeks. 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. ARB mitigates DN progression by reducing hyperglycemia, inflammation, and oxidative stress while strengthening antioxidant and signaling mechanisms involving Nrf2/HO-1 pathway.