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Nrf-2 mediated heme oxygenase-1 activation contributes to the anti-inflammatory and renal protective effects of Ginkgo biloba extract in diabetic nephropathy
- Source :
- Journal of ethnopharmacology. 266
- Publication Year :
- 2020
-
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.
- Subjects :
- Male
NF-E2-Related Factor 2
Anti-Inflammatory Agents
Pharmacology
Diet, High-Fat
Streptozocin
Podocyte
Diabetes Mellitus, Experimental
Nephrin
Diabetic nephropathy
03 medical and health sciences
Mice
0302 clinical medicine
Drug Discovery
medicine
Animals
Humans
Diabetic Nephropathies
Cells, Cultured
030304 developmental biology
0303 health sciences
Kidney
biology
Ginkgo biloba
Chemistry
Plant Extracts
Podocytes
biology.organism_classification
medicine.disease
Heme oxygenase
medicine.anatomical_structure
Mice, Inbred DBA
030220 oncology & carcinogenesis
Hyperglycemia
biology.protein
Synaptopodin
Reactive Oxygen Species
Heme Oxygenase-1
Lipoprotein
Subjects
Details
- ISSN :
- 18727573
- Volume :
- 266
- Database :
- OpenAIRE
- Journal :
- Journal of ethnopharmacology
- Accession number :
- edsair.doi.dedup.....a036af848888a3b5f775a0756d406bbd