Rhizome of Anemarrhena asphodeloides Bunge (AA, family Liliaceae) has been widely used in China for thousands of years to treat febrile diseases and diabetes. Steroidal
saponins from AA show good antidiabetes effects and ameliorate
diabetic complications. This study was designed to investigate the effects of
sarsasapogenin (Sar), a major sapogenin from AA, on
diabetic nephropathy (DN) in rats, and to explore the possible mechanisms. Diabetic rats were divided into 3 groups treated orally with Sar (0, 20, or 60 mg/kg) and
carboxymethylcellulose sodium, whereas normal rats for Sar (0 or 60 mg/kg) and
carboxymethylcellulose sodium. We found that chronic treatment with Sar for 9 weeks significantly ameliorated renal dysfunction of diabetic rats, as evidenced by decreases in
albuminuria, kidney weight index, serum
uric acid, and morphologic changes such as extracellular matrix expansion and accumulation (
fibronectin and
collagen IV levels, etc.). Meanwhile, Sar treatment resulted in decreases in
interleukin-18, NLRP3, and activated
caspase 1 levels as well as
advanced glycation endproducts (AGEs) and their receptor (RAGE) levels in the renal cortex of diabetic rats. However, Sar has no effects on the above indices in the normal rats. Therefore, Sar can markedly ameliorate
diabetic nephropathy in rats via inhibition of NLRP3
inflammasome activation and AGEs-RAGE interaction.