Abstract | BACKGROUND: In this study, we investigated the Nrf2/ARE signaling pathway activating capacity of Biphenyl Diester Derivative-39 (BDD-39) in diabetic nephropathy in order to elucidate the mechanism surrounding its antidiabetic potential. OBJECTIVES:
Protein expressions of Nrf2, HO-1, NQO-1 and biomarkers of kidney fibrosis were executed after which mRNA levels of Nrf2, HO-1 and NQO-1 were estimated after creating the models following BBD-39 treatment. METHODS:
Type 2 diabetes model was established in mice with high-fat diet feeding combined with streptozocin intraperitoneal administration. The diabetic mice were then treated with BDD-39 (15, 45mg· kg-1· d-1, ig) or a positive control drug resveratrol (45mg· kg-1·d-1, ig) for 8 weeks. Staining techniques were used to investigate collagen deposition in the glomerulus of the renal cortex and also to investigate the expression and localization of Nrf2 and extracellular matrix (ECM) proteins ( collagen IV and laminin) in vitro and in vivo. Furthermore, we studied the mechanism of action of BDD-39 using RNA-mediated Nrf2 silencing technique in mouse SV40 glomerular mesangial cells (SV40 GM cells). RESULTS: We found that BDD-39 activates Nrf2/ARE signaling pathway, promotes Nrf2 nuclear translocation (Nrf2nuc/Nrf2cyt) and modulate prominent biomarkers of kidney fibrosis at the protein level. However, BDD-39 could not activate Nrf2/ARE signaling in RNA-mediated Nrf2-silenced HG-cultured SV40 GM cells. CONCLUSION: Taken together, this study demonstrates for the first time that BDD-39 ameliorates experimental DN through attenuation of renal fibrosis progression and modulation of Nrf2/ARE signaling pathway.
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Authors | Temitope Adelusi, Xizhi Li, Liu Xu, Lei Du, Meng Hao, Xueyan Zhou, Apu Chowdhry, Ying Sun, Xiaoke Gu, Qian Lu, Xiaoxing Yin |
Journal | Current molecular pharmacology
(Curr Mol Pharmacol)
Vol. 15
Issue 4
Pg. 658-675
( 2022)
ISSN: 1874-4702 [Electronic] United Arab Emirates |
PMID | 34525927
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright© Bentham Science Publishers; For any queries, please email at [email protected]. |
Chemical References |
- Biphenyl Compounds
- Chalcone
- Chalcones
- diphenyl
- NF-E2-Related Factor 2
- RNA
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Topics |
- Animals
- Mice
- Biphenyl Compounds
- Chalcone
(therapeutic use)
- Chalcones
- Diabetes Mellitus, Experimental
- Diabetes Mellitus, Type 2
(drug therapy)
- Diabetic Nephropathies
(drug therapy, metabolism)
- Fibrosis
- NF-E2-Related Factor 2
(metabolism)
- Oxidative Stress
- RNA
(metabolism)
- Signal Transduction
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