Sinomenine improve diabetic nephropathy by inhibiting fibrosis and regulating the JAK2/STAT3/SOCS1 pathway in streptozotocin-induced diabetic rats

To investigate the therapeutic effects and potent mechanism of sinomenine (SIN) nanoliposomes on nephropathy in diabetic rats. The protective efficacies of SIN on the oxidative injury in renal HK-2 cell induced by hydrogen peroxide (H2O2) were investigated via the CCK-8 assay. Forty SD rats with streptozotocin (STZ)-induced diabetic kidney disease (DKD) were assigned to the saline group and three SIN groups (10, 20 and 40 mg/kg). During 6-week treatment, body weight, fasting glucose level and other metabolic parameters were recorded. H&E staining and changes in renal functions as well as expression levels of apoptosis and fibrosis-related factors in renal tissues were assessed. The qPCR and western blotting (WB) methods were used to detect relative expression levels of JAK/STAT/SOCS pathway-related factors in the renal tissues. Cell viabilities of HK-2 cells with oxidative injury were obviously improved by incubating with SIN at 320 μg/mL for 92.9%. Significantly up-regulated GPX1, SOD2 and GSH contributed to the down-regulated ROS content in SIN-treated groups. Moreover, 6-week administration of SIN improved renal functions and worsening nephropathy morphology of DKD rats. SIN also ameliorated gradually increased renal cell apoptosis, suppressed expression levels of fibrosis-related proteins as well as IL-6 and ICAM-1, and regulated JAK2/STAT3/SOCS1 pathway, thereby exhibited protective effects on renal tissues of DKD rats. SIN protects nephrocytes and decreases renal tissue injury via inhibiting oxidative stress, reducing renal cell apoptosis and fibrosis, regulating the JAK2/STAT3/SOCS1 pathway in DKD rats.