Jiangtang Capsule ameliorates kidney injury via inhibition of the JAK-STAT signaling pathway and increased antioxidant capacity in STZ-induced diabetic nephropathy rats

Diabetic nephropathy (DN), the most common and most serious microvascular complication of diabetic mellitus (DM), is a major cause of chronic renal failure or end-stage renal disease (ESRD). With the increase of the incidence of DM, the subsequent incidence of DN is increasing worldwide. Multiple mechanisms contribute to the occurrence and development of DN, such as glucose and lipid metabolic disorders, oxidative stress, accumulation of advanced glycosylation end products (AGEs) and the interaction with their receptors, and renal hemodynamic alterations. Accumulating evidence suggests that inflammation is an important pathogenic mechanism of diabetic complications (1-4). Elevated levels of proinflammatory cytokines, chemokines, adhesion molecules and growth factors in renal tissues, serum and urine of diabetic patients are correlated with albuminuria (1-4). During inflammation, Summary Danzhi Jiangtang Capsule (DJC), a traditional Chinese medicinal formula, has been used clinically in treating diabetes and diabetic nephropathy (DN). We previously demonstrated that DJC is capable of improving renal function in patients and rats with DN, but the mechanisms underlying these therapeutic benefits of DJC are not quite clear yet. In this study, STZ-induced diabetic rats were orally administered DJC for 8 weeks. Fasting blood glucose, renal function indicators in the serum, renal index, and the expression of proteins related to JAK-STAT signaling pathway were evaluated at the end of the experiment. The kidneys were sliced for pathological histology. Antioxidant status was assessed by measuring SOD, LPO and MDA in serum. The expression levels of COX2, iNOS, SOCS and the phosphorylation status of JAK2, STAT1, and STAT3 in renal tissues were evaluated by Western blot analyses. IL-6, TNF-α, and MCP-1 expression levels in renal tissues were determined using doubleantibody sandwich ELISA. Diabetic renal dysfunction and its associated pathologies were ameliorated by DJC treatment. DJC significantly reversed the high expression of COX2 and iNOS in renal tissues. Furthermore, DJC inhibited the JAK2-STAT1/STAT3-SOCS3 signaling pathway, resulting in decreased concentrations of IL-6, TNF-α, and MCP-1. Moreover, the oxidant status in the kidney was substantially ameliorated by DJC treatment. In conclusion, the ability of DJC to ameliorate diabetic renal dysfunction and the associated pathologies of this disease might be due to its antioxidant capacity and suppression of the JAK2-STAT1/ STAT3 cascade.