Alpinia oxyphylla alleviates diabetic nephropathy through the NLRP3 inflammasome pathway in rats

ABSTRACT

Objective: Previous studies have confirmed that the tropical traditional Chinese herb-Alpinia (A.) oxyphylla are effective on diabetic nephropathy. The purpose of this experiment was to investigate whether A. oxyphylla could prevent and treat diabetic nephropathy by regulating NLRP3 inflammasome pathway. Methods: Male SD rats and NLRP3 gene silencing rats were assinged into blank group, model group, A. oxyphylla group, valsartan group and NLRP3 gene silencing group, with 8 rats in each group. The model was established by intraabdominal injection of streptomycin after feeding with high sugar and high fat diet for 6 weeks. Based on successful modeling, administration protocal for a period of 8 weeks were performed. A. oxyphylla group was given A. oxyphylla decoction (2.6g/kg/d ), while the model group and NLRP3 gene silencing group were given saline as the same dosage of A. oxyphylla decoction. The valsartan (10 mg/kg/d) was given to the valsartan group. After 8 weeks of treatments, blood glucose, 24 h urinary protein, creatinine, urea nitrogen levels were detected, and the pathological sections of the kidney were examined. The expression of NLRP3 protein was detected by Western-Blot and PCR. NLRP3 protein, caspase-1, IL-18 and IL-1βin renal tubules were detected in each group by immunofluorescence and immunohistochemistry. Results: Compared with the model group, A. oxyphylla significantly reduced blood glucose, 24 h urinary protein, creatinine, urea nitrogen levels (P all<0.05) but the pathological injury in kidney was less. The expression of NLRP3 protein was negative in NLRP3-/-group while positive in the model group, A. oxyphylla group and valsartan group. Expression of NLRP3 protein, NLRP3, caspase-1, IL-18 and IL-1β were also significantly lower in A. oxyphylla trated group compared with the model group (P all<0.05). Conclusions: A. oxyphylla could inhibit the expression of NLRP3 protein, reduce IL-18 and IL-1β and other inflammatory factors and alleviate the damage of kidney caused by inflammatory reaction. This is one of the mechanisms whereby A. oxyphylla prevents and treats diabetic nephropathy.