Schisandrin ameliorates diabetic nephropathy via regulating of PI3K/Akt/NF-κB-mediated inflammation and TGF-β1-induced fibrosis in HFD/STZ-induced C57BL/6J mice

Abstract

In the present work, we investigated the protective effect of schisandrin, a major and representative lignin from the fruits of Schisandra chinensis Baill., on streptozotocin combining with high fat diet (STZ/HFD)-induced diabetic nephropathy (DN) in mice. All mice were divided into five groups as follows: normal group, diabetes mellitus (DM) group, Metformin group, DM + schisandrin (10 and 20 mg/kg). Schisandrin were administered intragastrically to mice for 8 weeks. Schisandrin prevented DN-induced injuries as determined by significantly decreasing levels of fast blood glucose, advanced glycation end products (AGEs), lipid Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), creatinine (CRE), and blood urea nitrogen (BUN) and increasing level of high-density lipoprotein cholesterol (HDL-C), which correlated with inhibited TGF-β1 and α-SMA at protein and transcriptional levels. In addition, schisandrin treatment reduced protein expression levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), inducible nitric oxide synthase (iNOS), and cyclooxygenase (COX-2), suggesting a suppressed inflammatory response. This suppression was afforded by inhibiting nuclear factor-κB (NF-κB) and activating phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt) signaling. In summary, these findings highlight the nephroprotective effect of schisandrin against STZ/HFD-induced DN through inhibiting the renal inflammation and fibrosis in mice.

Keywords

• Schisandrin
• Diabetic Nephropathy
• PI3K/Akt
• NF-κB
• Inflammation