Polydatin Ameliorates High Fructose-Induced Podocyte Oxidative Stress via Suppressing HIF-1α/NOX4 Pathway

Long-term high fructose intake drives oxidative stress, causing glomerular podocyte injury. Polydatin, isolated from Chinese herbal medicine Polygonum cuspidatum, is used as an antioxidant agent that protects kidney function. However, it remains unclear how polydatin prevents oxidative stress-driven podocyte damage. In this study, polydatin attenuated high fructose-induced high expression of HIF-1 alpha, inhibited NOX4-mediated stromal cell-derived factor-1 alpha/C-X-C chemokine receptor type 4 (SDF-1 alpha/CXCR4) axis activation, reduced reactive oxygen species (ROS) production in rat glomeruli and cultured podocytes. As a result, polydatin up-regulated nephrin and podocin, down-regulated transient receptor potential cation channel 6 (TRPC6) in these animal and cell models. Moreover, the data from HIF-1 alpha siRNA transfection showed that high fructose increased NOX4 expression and aggravated SDF-1 alpha/CXCR4 axis activation in an HIF-1 alpha-dependent manner, whereas polydatin down-regulated HIF-1 alpha to inhibit NOX4 and suppressed SDF-1 alpha/CXCR4 axis activation, ameliorating high fructose-induced podocyte oxidative stress and injury. These findings demonstrated that high fructose-driven HIF-1 alpha/NOX4 pathway controlled podocyte oxidative stress damage. Intervention of this disturbance by polydatin could help the development of the therapeutic strategy to combat podocyte damage associated with high fructose diet.

Automated summary

This study found that high fructose intake can lead to oxidative stress and injury in glomerular podocytes. Polydatin, a compound extracted from Chinese herbal medicine, can attenuate this damage by inhibiting the activation of the HIF-1α, NOX4, and SDF-1α/CXCR4 pathways. These findings suggest that polydatin may be a potential therapeutic strategy for protecting podocytes against oxidative stress and injury induced by high fructose intake.