Astragalus Polysaccharide Ameliorates Renal Inflammatory Responses in a Diabetic Nephropathy by Suppressing the TLR4/NF-κB Pathway

Background: Diabetic nephropathy (DN), as a chronic inflammatory complication of diabetes, is characterized by hyperglycemia, albuminuria and edema, which ultimately becomes the leading cause of end-stage renal disease (ESRD). Astragalus polysaccharide (APS), extracted from the Astragalus membranaceus, was widely used in the treatment of diabetes mellitus. However, the functional roles of APS ameliorate inflammatory responses in DN, which remain poorly understood. Therefore, the purpose of this study was to explore the molecular mechanism of APS on DN in vivo and vitro models. Methods: We explored the beneficial effects of APS in streptozotocin (STZ)-induced DN rat model and high glucose (HG)-treated glomerular podocyte model. The fasting blood glucose (FBG) and ratio of kidney weight to body weight were measured after 4 weeks of APS treatment. The renal injury parameters containing serum creatinine (Scr), blood urea nitrogen (BUN) and 24 h urinary protein were evaluated. The renal pathological examination was observed by hematoxylin-eosin (HE) staining. The levels of IL-1 & beta;, IL-6 and MCP-1 were evaluated by ELISA assay. The proliferation of podocytes was determined using CCK-8 assay and flow cytometry. qRTPCR and Western blot analysis were performed to determine the amounts of TLR4/NF-& kappa;B-related gene expression. Results: Our results indicated that APS effectively decreased the levels of FBG, BUN, Scr and renal pathological damage when compared with STZ-induced DN model group. Additionally, APS significantly ameliorated renal injury by reducing inflammatory cytokines IL-1 & beta;, IL-6, MCP-1 expression and inhibiting the TLR4/NF-& kappa;B pathway activity in DN rats. Consistent with the results in vitro, the HG-induced inflammatory response and proliferation of glomerular podocytes were also alleviated through APS administration. Conclusion: We found that APS ameliorated DN renal injury, and the mechanisms perhaps related to relieving inflammatory responses and attenuating the TLR4/NF-& kappa;B signaling pathway.

Automated summary

Diabetic nephropathy is a chronic inflammatory complication of diabetes characterized by hyperglycemia, albuminuria, and edema. Astragalus polysaccharide, extracted from Astragalus membranaceus, has been used for the treatment of diabetes mellitus. This study aimed to investigate the molecular mechanism of Astragalus polysaccharide on diabetic nephropathy. The results demonstrated that Astragalus polysaccharide effectively reduced fasting blood glucose levels, improved kidney function, and alleviated renal pathological damage in diabetic nephropathy models.