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Nobiletin ameliorates streptozotocin-cadmium-induced diabetic nephropathy via NF-κB signalling pathway in rats
Mingzhu Xu1, Ruifang Wang1, Hui Fan1
1Department of Nephrology, China-Japan Union Hospital of Jilin University Changchun, Jilin, China.
Abstract:
This study sought to examine the anti-diabetic effect of nobiletin on streptozotocin (STZ)/cadmium (Cd)-induced diabetic nephrotoxic (DN) rats. The DN was induced using STZ (40 mg/kg b.w) intraperitoneally and Cd through drinking water for 12 weeks. The DN rats were treated with nobiletin of different concentrations (10, 20, and 40 mg/kg/BW). The STZ/Cd-induced DN leads to a significantly increased of the glucose levels, glycosylated haemoglobin, hepatic and kidney function markers, lipid peroxidation levels, and reduction of insulin levels, total haemoglobin, body weight, and antioxidant status markers. Our finding that nobiletin pathological impairment and diminished infiltration of neutrophil in kidney tubules and all biochemical enzymes were near normal levels in DN. More essentially, nobiletin strongly impedes the protein expression of renal nuclear NF-κB p65. Bax protein expression was significantly downregulated and elevated protein expression Bcl-2 was recorded in DN rats. These results show that nobiletin possesses antioxidant as well as anti-diabetic activities and thereby reduces chronic kidney diseases in rats.
Insights
Nobiletin demonstrates significant anti-diabetic and antioxidant effects, improving kidney function in diabetic nephrotoxic rats. It effectively reduces hyperglycemia and kidney damage by modulating key protein expressions.
Area of Science:
- Pharmacology
- Nephrology
- Biochemistry
Background:
- Diabetic nephrotoxicity (DN) is a severe complication of diabetes, characterized by kidney damage.
- Streptozotocin (STZ) and cadmium (Cd) are commonly used to induce experimental DN in animal models.
- Oxidative stress and inflammation play critical roles in the pathogenesis of DN.
Purpose of the Study:
- To investigate the protective effects of nobiletin against STZ/Cd-induced diabetic nephrotoxicity in rats.
- To evaluate the anti-diabetic and antioxidant potential of nobiletin.
- To elucidate the molecular mechanisms underlying nobiletin's action in DN.
Main Methods:
- Diabetic nephrotoxicity was induced in rats using STZ and Cd.
- Rats were treated with varying concentrations of nobiletin (10, 20, 40 mg/kg/BW).
- Biochemical parameters, kidney function markers, oxidative stress markers, and protein expressions (NF-κB p65, Bax, Bcl-2) were assessed.
Main Results:
- Nobiletin treatment significantly improved glucose levels, glycosylated hemoglobin, and kidney/hepatic function markers.
- Nobiletin reduced lipid peroxidation and enhanced antioxidant status in DN rats.
- Nobiletin inhibited renal NF-κB p65 expression and modulated Bax/Bcl-2 protein levels, indicating reduced apoptosis and inflammation.
Conclusions:
- Nobiletin exhibits potent anti-diabetic and antioxidant properties, ameliorating STZ/Cd-induced nephrotoxicity.
- Nobiletin protects kidneys by reducing oxidative stress, inflammation, and apoptosis.
- Nobiletin represents a potential therapeutic agent for managing diabetic kidney disease.
