Nrf-2 mediated heme oxygenase-1 activation contributes to the anti-inflammatory and renal protective effects of Ginkgo biloba extract in diabetic nephropathy

Ting Ting Chang, Yi An Chen, Szu Yuan Li, Jaw-Wen Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Ethnopharmacological relevance: Ginkgo biloba extract (GbE) is derived from a medicinal plant and suggested as a treatment for diabetic nephropathy (DN), but the mechanism was not clarified. Aim of study: The present study investigated whether GbE prevented DN via activation of heme oxygenase (HO)-1. Materials and methods: Streptozotocin-induced diabetic mice were fed a high-fat diet to generate DN. Human and murine podocytes were used for the in vitro study. Results: GbE improved renal function via decreasing glomerular hypertrophy, the kidney/body weight ratio, and albuminuria in DN mice. GbE reversed the reduction of synaptopodin and nephrin and enhanced HO-1 expression in the kidneys of DN mice. GbE decreased the enhancement of TNF-α, IL-6, fibronectin, and lipid accumulation in the glomeruli of DN mice. GbE attenuated the uptake of oxidized low-density lipoprotein and reduced the production of ROS in high glucose-stimulated podocytes, and HO-1 inhibitor treatment abrogated the protective effects of GbE. Nuclear factor erythroid 2-related factor 2 (Nrf-2) siRNA significantly abolished the beneficial effects of GbE via decreased HO-1 expression and enhanced TNF-α and IL-6 levels. Conclusions: GbE protected podocytes against hyperglycemia and prevented the development of DN via Nrf-2/HO-1 activation. Our findings provide further mechanistic insight into the potential use of GbE in clinical DN.

Original languageEnglish
Article number113474
JournalJournal of Ethnopharmacology
Volume266
DOIs
StatePublished - 10 Feb 2021

Keywords

  • Diabetic nephropathy
  • Ginkgo biloba extract
  • Heme oxygenase −1
  • Podocyte
  • Proteinuria

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