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- Title
Therapeutic potential of digitoflavone on diabetic nephropathy: nuclear factor erythroid 2-related factor 2-dependent anti-oxidant and anti-inflammatory effect.
- Authors
Yang, Yang; Chen, Gang; Cheng, Xiaolan; Teng, Zhiying; Cai, Xueting; Yang, Jie; Sun, Xiaoyan; Lu, Wuguang; Wang, Xiaoning; Yao, Yuanzhang; Hu, Chunping; Cao, Peng
- Abstract
Nuclear factor erythroid 2-related factor 2 (Nrf2) has emerged as a therapeutic target in many diseases, because it can induce antioxidant enzymes and other cytoprotective enzymes. Moreover, some Nrf2 activators have strong anti-inflammatory activities. Oxidative stress and inflammation are major components involved in the pathology of diabetic nephropathy. In the present study, we evaluated the Nrf2-dependent anti-oxidative and anti-inflammatory effects of digitoflavone in streptozotocin-induced diabetic nephropathy. The molecular mechanisms of digitoflavone were investigated in vitro using SV40-transformed mouse mesangial cells (SV40-Mes13). For the in vivo experiment, diabetes was induced in Nrf2+/+ and Nrf2−/− mice by STZ injection, and digitoflavone was administered 2 weeks after the STZ injection. Digitoflavone induced Nrf2 activation and decreased oxidative damage, inflammation, TGF-β1 expression, extracellular matrix protein expression, and mesangial cell hyperplasia in SV40-Mes13 cells. Digitoflavone-treated Nrf2+/+ mice, but not Nrf2−/− mice, showed attenuated common metabolic disorder symptoms, improved renal performance, minimized pathological alterations, and decreased oxidative damage, inflammatory gene expression, inflammatory cell infiltration, TGF-β1 expression, and extracellular matrix protein expression. Our results show that the anti-oxidative and anti-inflammatory effects of digitoflavone are mediated by Nrf2 activation and that digitoflavone can be used therapeutically to improve metabolic disorders and relieve renal damage induced by diabetes.
- Subjects
FLAVONES; TRANSCRIPTION factors; DIABETIC nephropathies; STREPTOZOTOCIN; ANTIOXIDANTS; ANTI-inflammatory agents; OXIDATIVE stress; INFLAMMATION; THERAPEUTICS
- Publication
Scientific Reports, 2015, p12377
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/srep12377