Protective Role of Oryeongsan Against Renal Inflammation and Glomerulosclerosis in db/db Mice

Abstract

Diabetic nephropathy is characterized by renal hardening and interstitial fibrosis caused by extracellular matrix (ECM) accumulation. The most distinctive diabetic lesion in the glomeruli is mesangial expansion and hyperplasia, which ultimately leads to diabetic nephrosclerosis. Oryeongsan (ORS), a traditional Chinese herbal medication, is widely used to treat nephrosis, dropsy, and uremia. In this study, type 2 diabetic animals (db/db mice) were administered ORS (100 mg/kg/day) for 8 weeks to examine the potential beneficial effects on metabolic abnormalities and diabetic nephropathy progression, including renal fibrosis. The body weight, total-cholesterol, triglyceride, and LDL-c levels were significantly decreased in ORS-treated db/db mice compared to untreated db/db mice. In addition, the blood glucose, insulin, glucose tolerance, and the homeostasis model assessment of insulin resistance index (HOMA-IR) were significantly improved in ORS-treated db/db mice compared to untreated db/db mice. Creatinine clearance (Ccr), urine albumin, and BUN levels were also improved by ORS treatment. The ratio of mesangial matrix/glomerular area was markedly higher in db/db mice than in db/m mice, but ORS significantly reduced this expansion. TGF-β1, Smad-2/-4, Collagen IV, CTGF, and TIMP decreased with ORS treatment, as were Smad-7 and MT1-MMP in ORS-treated db/db mice. Furthermore, ICAM-1 and MCP-1 expression were suppressed in ORS-treated db/db mice. Therefore, these findings suggest that ORS ameliorated insulin resistance and diabetes-associated glomerulosclerosis in db/db mice, possibly by disturbing the TGF-β1/Smads pathway. ORS may be a new therapeutic option for treating diabetic nephropathy.