A Nucleoside/Nucleobase-Rich Extract from Cordyceps Sinensis Inhibits the Epithelial–Mesenchymal Transition and Protects against Renal Fibrosis in Diabetic Nephropathy

Cordyceps Sinensis, a traditional Chinese medicine and a healthy food, has been used for the treatment of kidney disease for a long time. The aim of present study was to isolate a nucleoside/nucleobase-rich extract fromCordyceps Sinensis(CS-N), determine the contents of nucleosides and nucleobases, and explore its anti-diabetic nephropathy activity. CS-N was isolated and purified by using microporous resin and glucan columns and the unknown compounds were identified by using HPLC-DAD and LC-MS. The effects of CS-N on the epithelial–mesenchymal transition (EMT), extracellular matrix (ECM) depositions, and the MAPK signaling pathway were evaluated in streptozotocin (STZ)-induced diabetic mice and high glucose (HG)-exposed HK-2 cells. CS-N significantly attenuated the abnormity of renal functional parameters, ameliorated histopathological changes, and inhibited EMT and ECM accumulation by regulating p38/ERK signaling pathways. Our findings indicate that CS-N exerts a therapeutic effect on experimental diabetic renal fibrosis by mitigating the EMT and the subsequent ECM deposition with inhibition of p38 and ERK signaling pathways.Keywords:nucleosides and nucleobases;diabetic nephropathy;HK-2 cells;extracellular matrix;epithelial–mesenchymal transition