Abstract: FR-PO618

Puerarin Attenuates Diabetic Kidney Injury through Suppression of NOX4 Expression in Podocytes

Session Information

Category: Diabetes

  • 501 Diabetes Mellitus and Obesity: Basic - Experimental

Authors

  • Zhong, Yifei, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, China, Shanghai, Shanghai, China
  • Liu, Ruijie, Mount Sinai School of Medicine, New York, New York, United States
  • Lee, Kyung, Mount Sinai School of Medicine, New York, New York, United States
  • He, John C., Mount Sinai School of Medicine, New York, New York, United States
Background

Radix puerariae, a traditional Chinese herbal medication, has been used to treat patients with diabetic nephropathy (DN). Several studies demonstrated that puerarin, the active compound of radix puerariae, improves DN in streptozotocin (STZ)-induced rat and mouse models. However, as STZ injection alone results in mild kidney injury, the mechanisms of renoprotection afforded by puerarin remained inconclusive. Therefore in this study, we sought to clarify the role of puerarin by employing a STZ-induced diabetes in the mice lacking the endothelial nitric oxide synthase, which develop more advanced DN, and explored the mechanism of puerarin in cultured podocytes.

Methods


Diabetes was induced in the male eNOS homozygous knockout mice of 8 weeks old on a C57BL/6 background by injecting streptozotocin for 5 consecutive days. 2 weeks after diabetes was confirmed in mice, mice were given puerarin (Sigma-Aldrich) by oral gavage at a dose of 20mg/kg body weight/day, or vehicle as control, for 8 weeks. Urine albuminuria, kidney histology, IHC, and qPCR of isolated glomeruli were analyzed as desscribed. Conditionally immortalized murine podocytes were obtained from Dr. Peter Mundel. Podocytes were transfected using Viafect reagent and ROS and NAPDH oxidase activity were measured accordingly.

Results

Puerarin treatment of diabetic eNOS-/- mice significantly improved albuminuria and diabetic kidney injury. Puerarin also significantly reduced oxidative stress and inhibited the expression of NAPDH oxidase 4 (NOX4) in glomeruli of diabetic mice. In cultured conditionally immortalized murine podocytes, puerarin reduced superoxide production, as well as NOX4 expression at both mRNA and protein levels. Interestingly, we found that puerarin increased both mRNA and protein levels of Sirt1 in podocytes. Indeed, puerarin suppressed NOX4 expression through Sirt1-mediated deacetylation of NF-κB.

Conclusion

Our findings confirm the renal protective effects of puerarin in an animal model with more advanced DN and demonstrate a new mechanism that underlies the anti-oxidative effects of puerarin in kidney podocytes.

Funding

  • Government Support - Non-U.S.