Emerging evidence shows that increasing fibrosis and apoptosis have been observed in the tubular epithelia in the progression of type 1 diabetic nephropathy (DN). Excessive inflammatory response and oxidative stress contribute to the pathogenesis of progression. Isoliquiritigenin (ISL), a natural chalcone compound, has been reported to exert anti-inflammatory and anti-oxidative properties. However, little is known about the effects of ISL on diabetic nephropathy and its mechanism. In this study, we investigated the potential protective effects and pharmacological mechanisms of ISL on DN in vivo and in vitro. We test beneficial activities of ISL on streptozotocin (STZ)-induced type 1 diabetes mellitus mice and renal tubular epithelial NRK-52E cells. The study showed that ISL attenuated diabetic nephropathy by decreasing both pro-fibrotic and pro-apoptotic biomarkers. Diabetes or high glucose (HG) induced inflammatory response and oxidative stress were eliminated by ISL administration. The molecular docking using the multiple ligand simultaneous docking (MLSD) software indicated that three molecules of ISL might bound to the binding site of SIRT1 and formation of a stable complex. We also found ISL could neutralize HG-mediated inactivation of SIRT1. Activation of SIRT1 could attenuate HG-induced inflammation, oxidative stress, fibrosis and apoptosis in NRK-52E cells, paralleled with the effects of ISL. While inhibition of SIRT1 could significantly abrogate the protective effects of ISL. Our study implicated that ISL might have great pharmacological actions on attenuating tubular damage of diabetic nephropathy. The beneficial effects of ISL are likely associated with inhibiting excessive inflammatory response and oxidative stress via directly activating SIRT1.


X. Chen: None. F. Shen: None.


Wenzhou Science and Technology Bureau (Y20190125); First Affiliated Hospital of Wenzhou Medical University (FHY2019015)

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