Samchuleum suppressed high glucose‐induced renal proliferation and fibrosis in cultured rat mesangial cells

Abstract

Diabetic nephropathy associated with morbidity and mortality of diabetic patients. Mesangial cell proliferation is known as the major pathologic features such as glomerulosclerosis and renal fibrosis. Samchuleum (SCE), originally recorded in an ancient Korea medicinal book named “Donguibogam”, is a well‐known blended traditional herbal formula. Thus, this study was investigated the inhibitory effect of SCE (1‐50 μg/ml) on high glucose (HG)‐stimulated rat mesangial cells proliferation and fibrosis.Thymidine incorporation under HG was significantly accelerated, which was inhibited by SCE in a dose dependent manner. Pre‐treatment of SCE induced down‐regulation of cyclins/CDKs and up‐regulation of CDK inhibitor, p21waf1/cip1 and p27kip1 expression. In addition, SCE significantly suppressed the HG‐induced ROS production. Thus, SCE consequently inhibited HG‐induced mesangial cell proliferation through the inhibition of ROS signaling pathway.HG enhanced expression of fibrosis biomarkers such as collagen IV and CTGF, which was markedly attenuated by SCE. Moreover, SCE inhibits HG‐induced fibronectin mRNA expression. SCE decreased TGF‐β1 and p‐Smad2/Smad4 expression, whereas increased Smad7 expression under HG. Thus, SCE promoted ECM degradation through disturbing TGF‐β–SMAD signaling.In conclusion, these results suggested that SCE has a protective effect on renal proliferation and fibrosis. Thus SCE might prove to be effective in the treatment of renal dysfunction leading to Diabetic nephropathy.