Isoliquiritigenin Alleviates Diabetic Kidney Disease via Oxidative Stress and the TLR4/NF-κB/NLRP3 Inflammasome Pathway

Diabetic kidney disease (DKD) is the primary factor that causes chronic kidney disease and causes increasing mortality and morbidity due to its severe consequences. Isoliquiritigenin (ISL) is the primary element of licorice root that is physiologically active and has antifree radical, antioxidation, and antiapoptotic properties. However, the effect of ISL on DKD is still unclear and needs to be further improved. This study aims to evaluate the renoprotective effects of ISL on diabetes-induced renal injury and explores the underlying mechanisms involved. Male C57BL/6 mice are fed a high-fat diet and then injected with streptozotocin for 2 consecutive days to establish a diabetic model, and high-glucose-treated NRK-52E cells are used to investigate the renoprotective effects of ISL in DKD. The results show that ISL significantly preserves renal function and architecture in DKD. ISL suppresses oxidative stress and reduces ROS levels, inhibiting the activation of the NF-κB and the NLRP3 inflammasome and the occurrence of pyroptosis. Moreover, the study finds that ISL can inhibit the mitochondrial apoptotic pathway. In addition, the study confirms the inhibitory effect of ISL on the TLR4/NF-κB/NLRP3 inflammasome pathway. These observations demonstrate that the natural flavonoid compound ISL can be a promising agent for the treatment of DKD.