Abstract
In human diabetic nephropathy, the extent of tubulointerstitial fibrosis is the leading cause of end-stage renal disease; fibrosis is closely correlated with renal dysfunction. Although a wide array of medicinal plants play a role in the prevention and treatment of diabetes, there are few reports of the application of herbal medicines in amelioration of renal fibrosis, or the underlying mechanisms by which such benefits are mediated. The efficacy of the Ayurvedic antidiabetic medicine Salacia oblonga (SO) root on rat renal fibrosis was investigated. An aqueous extract from SO (100 mg/kg, p.o., 6 weeks) diminished renal glomerulosclerosis and interstitial fibrosis in Zucker diabetic fatty (ZDF) rats, as revealed by van Giesen-staining. SO also reduced renal salt-soluble, acid-soluble and salt-insoluble collagen contents. These changes were accompanied by normalization of hypoalbuminemia and BUN. Gene profiling revealed that the increase in transcripts encoding the glomerulosclerotic mediators collagen I, collagen IV, fibronectin, angiotensin II type 1 receptor (AT1), transforming growth factor (TGF)-β1, plasminogen activator inhibitor (PAI)-1 observed in ZDF rat kidney was suppressed by SO. In rat-derived mesangial cells, similar to the effect of the AT1 antagonist telmisartan, SO and its major component mangiferin suppressed the stimulatory effect of angiotensin II on proliferation and increased mRNA expression and/or activities of collagen I, collagen IV, fibronectin, AT1, TGF-β1 and PAI-1. Considered together the present findings demonstrate that SO attenuates diabetic renal fibrosis, at least in part by suppressing anigiotensin II/AT1 signaling. Further, it now emerges that mangiferin is an effective antifibrogenic agent.
Highlights
Fibroproliferative diseases, including cardiovascular disease, progressive kidney disease and macular degeneration, are leading causes of morbidity and mortality and can affect all tissues and organ systems
Diabetic nephropathy is structurally characterized by an early thickening of tubular and glomerular basement membranes due to the excessive accumulation of the extracellular matrix [2]
The extent of glomerulosclerosis and tubulointerstitial fibrosis are well correlated with renal dysfunction [4,5,6]
Summary
Fibroproliferative diseases, including cardiovascular disease, progressive kidney disease and macular degeneration, are leading causes of morbidity and mortality and can affect all tissues and organ systems. Diabetic nephropathy is the leading cause of end-stage renal disease worldwide and is an independent risk factor for all-cause and cardiovascular mortalities in diabetic patients. Diabetic nephropathy is structurally characterized by an early thickening of tubular and glomerular basement membranes due to the excessive accumulation of the extracellular matrix [2]. Excessive deposition of extracellular matrix in the glomerular mesangium and tubulointerstitium is closely associated with a progressive decline in renal function in diabetes [2, 3]. The extent of glomerulosclerosis and tubulointerstitial fibrosis are well correlated with renal dysfunction [4,5,6]. Prevention and treatment of renal fibrosis may improve renal dysfunction
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