Cardamomin protects from diabetes-induced kidney damage through modulating PI3K/AKT and JAK/STAT signaling pathways in rats

Diabetic nephropathy is one of the common complications of diabetes mellitus, which seriously affects the life quality and health of patients. In this study, we aimed to investigate the function of cardamonin (CAD) in diabetes-induced kidney damage in rats.

The normal rat kidney tubular epithelial cells (NRK-52E) were pre-treated with different doses of CAD and then stimulated with methylglyoxal (MGO). Streptozotocin (STZ) induced diabetes rat model were received different doses of CAD treatment. MTT, EdU, Transwell, and flow cytometry was used to detect cell viability, proliferation, migration, and apoptosis. Western blot analysis was used to detect the expression of apoptosis related proteins, advanced glycation end-products (AGEs), receptor for AGEs (RAGE), epithelial mesenchymal transition (EMT) related proteins, phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway related proteins, and janus kinas/signal transducer and activator of transcription 3 (JAK/STAT3) related proteins. ELISA assay was used to detect the levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β). The levels of malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were detected using commercial kit. Hematoxylin and eosin staining was used to assess pathological changes in rat kidney.

Compared with control group, MGO reduced cell viability and proliferation, enhanced migration and apoptosis of NRK-52E cells, while CAD inhibited these effects induced by MGO in NRK-52E cells. Moreover, CAD increased Bcl-2 expression and decreased the expression of Bax and cleaved caspase-3 in MGO-treated NRK-52E cells. Compared with control group, MGO increased the AGEs formation, the expression of RAGE and p-p65, the levels of TNF-α, IL-6, IL-1β, MDA in NRK-52E cells and reduced the levels of GSH and SOD, while treatment of CAD dose-dependently prevented these results. In addition, CAD attenuated MGO-induced EMT of MGO-treated NRK-52E cells. Mechanically, we identified that CAD repressed PI3K/AKT and JAK/STAT3 signaling in NRK-52E cells. Importantly, the kidney injury of diabetes rats was attenuated by CAD. Besides, STZ-induced inflammatory response, oxidative stress, and phosphorylation levels of PI3K, AKT, JAK2, and STAT3 were reduced by CAD in the rats.

CAD protects from diabetes-induced kidney damage through modulating PI3K/AKT and JAK/STAT signaling pathways in rats.