Study on the inhibitive effect of Catalpol on diabetic nephropathy

Aims: Catalpol (Cat) can ameliorate oxide stress and inflammation caused by diabetic nephropathy (DN), but the molecular mechanisms are unclear. This study was designed to investigate the anti-diabetic effects of Cat and its potential mechanism. Main methods: We constructed high-fat diet/streptozotocin (HFD/STZ)-induced DN mice and high glucose (HG) induced podocyte model. The hypoglycemic effect of Cat was analyzed by general features of DN mice. Kidney function was detected via ELISA assay and Western blotting. Renal histopathology analysis was conducted via hematoxylin and eosin (H&E), Masson and periodic acid-silver metheramine (PASM) staining. Cellular viability was measured by TUNEL assay. In order to further study the potential mechanisms of Cat, various proteins in AMPK/SIRT1/NF-kappa B pathway were detected in DN mice and podocytes with siRNA-AMPK intervention using Western blotting, respectively. Key findings: We found hyperglycemia, renal structural and function abnormalities, and increased renal inflammation in DN mice. However, Cat effectively attenuated kidney damage caused by inflammation and increased AMPK, p-AMPK and SIRT1 levels. After AMPK-siRNA transfected into HG-induced podocyte model, AMPK, p-AMPK and SIRT1 levels were obviously decreased, while Cat reversed these chandes. The levels of pNF-kappa B, ASC, Cleaved IL-1 beta, NLRP3, Cleaved caspase1 and GSDMD-N significantly decreased by Cat treatment both in DN mice and podocyte model, which indicated that Cat could activate AMPK/SIRT1/NF-kappa B pathway. Significance: Cat could effectively inhibit oxide stress and inflammation accompanied with pyroptosis and its mechanism might be related to AMPK/SIRT1/NF-kappa B pathway, indicating that Cat possessed potential value in the treatment of DN.