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Fucoxanthin regulates Nrf2 signaling to decrease oxidative stress and improves renal fibrosis depending on Sirt1 in
Guanyu Yang1, Qingde Li2, Jing Peng2
1Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou, 570228, China.
Abstract:
Diabetic nephropathy (DN) is one of the major microvascular complications of diabetes. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a crucial cellular defense factor to cope with oxidative stress. Silent information regulator T1 (Sirt1) is a deacetylase with antioxidative stress activity. Fucoxanthin is a marine-derived carotenoid. This study was conducted to investigate whether fucoxanthin could alleviate oxidative stress by activating Sirt1/Nrf2 signaling to alleviate DN. In streptozotocin-induced diabetic rats, fucoxanthin treatment effectively improved renal function, alleviated glomerulosclerosis. Fucoxanthin reversed the decreased protein levels of Sirt1 and Nrf2 in the kidney of diabetic rats and glomerular mesangial cells cultured in high glucose. Conversely, EX527, a Sirt1 inhibitor, counteracted the effect of fucoxanthin on the expression of Nrf2. Furthermore, in vivo and vitro results showed that fucoxanthin treatment reversed the low expression and activity of superoxide dismutase and heme oxygenase 1, depending on Sirt1 activation. Our results suggest that fucoxanthin improves diabetic kidney function and renal fibrosis by activating Sirt1/Nrf2 signaling to reduce oxidative stress.
Insights
Fucoxanthin, a marine carotenoid, improves diabetic kidney disease by activating Sirt1/Nrf2 signaling, reducing oxidative stress and renal fibrosis in diabetic rats.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Diabetic nephropathy (DN) is a severe complication of diabetes, characterized by oxidative stress.
- Nuclear factor erythroid 2-related factor 2 (Nrf2) and Silent information regulator T1 (Sirt1) are key regulators of cellular defense against oxidative stress.
Purpose of the Study:
- To investigate if fucoxanthin alleviates diabetic nephropathy by activating Sirt1/Nrf2 signaling.
- To explore the potential of fucoxanthin as a therapeutic agent for diabetic kidney disease.
Main Methods:
- Streptozotocin-induced diabetic rat model and high glucose-cultured rat glomerular mesangial cells.
- Assessment of renal function, glomerulosclerosis, protein levels of Sirt1 and Nrf2, and activity of antioxidant enzymes.
- Utilized Sirt1 inhibitor (EX527) to confirm the role of Sirt1.
Main Results:
- Fucoxanthin treatment improved renal function and reduced glomerulosclerosis in diabetic rats.
- Fucoxanthin increased Sirt1 and Nrf2 protein levels in kidneys and mesangial cells.
- Fucoxanthin enhanced the expression and activity of superoxide dismutase and heme oxygenase 1, dependent on Sirt1 activation.
Conclusions:
- Fucoxanthin ameliorates diabetic nephropathy by activating Sirt1/Nrf2 signaling pathway.
- This activation leads to reduced oxidative stress and renal fibrosis, suggesting therapeutic potential for diabetic kidney disease.
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