Oryeongsan improves diabetes‐associated renal proliferation and fibrosis in cultured rat mesangial cells

Abstract

Diabetic nephropathy (DN) associated with morbidity and mortality of diabetic patients. Mesangial cell proliferation is known as the major pathologic features such as glomerulosclerosis and renal fibrosis. Oryeongsan (ORS), traditional herbal formula, is widely used for the treatment of nephrosis, dropsy, and uremia.Thymidine incorporation under HG was significantly accelerated, which was inhibited by ORS in a dose dependent manner. Pretreatment of ORS induced down‐regulation of cyclins/CDKs and up‐regulation of CDK inhibitor, p21waf1/cip1 and p27kip1 expression. In addition, ORS reduced HG‐induced RMCs proliferation by suppression of the MAPK phospholyration such as ERK, JNK, and p38. ORS significantly suppressed the HG‐induced ROS production.HG enhanced expression of □brosis biomarkers such as collagen IV and CTGF, which was markedly attenuated by ORS. Moreover, ORS inhibits HG‐induced fibronectin mRNA expression. ORS decreased TGF‐â1 and p‐Smad2/Smad4 expression, whereas increased Smad7 expression under HG. Thus, ORS promoted ECM degradation through disturbing TGF‐â– SMAD signaling.Taken together, these results demonstrate that ORS has a protective effect on renal proliferation and fibrosis. These results suggest that ORS might prove to be effective in the treatment of renal dysfunction leading to DN.