Effect of Onpi-to (TJ-8117) on TGF-beta 1 in rats with 5/6 nephrectomized chronic renal failure

We and others have already reported that Onpi-to (TJ-8117), a Kampo medicine composed mainly of Rhei Rhizoma, has a beneficial effect on an adenine-induced renal failure model and 5/6 nephrectomized renal failure. However, little is known about the detailed mechanism of this medicine when used for renal failure. The present study was designed to clarify whether or not TJ-8117 affects TGF-beta 1 production or activation in glomeruli of 5/6 nephrectomized rats. TJ-8117 (400 mg/kg/ day) and captopril (50 mg/kg/day) were administered as drinking water from the day immediately after the operation and continued throughout the experiment. All rats were sacrificed at 4 weeks and renal cortical tissue was removed to quantify the protein and activity of TGF-beta 1 and activities of metalloproteinase. TIMP expression and extracellular matrix (collagen type I, IV) in the glomeruli were analysed histologically. TJ-8117 inhibited proteinuria, and the accumulation of collagen type I and IV in glomeruli of nephrectomized rats. In addition, TJ-8117 inhibited the TGF-beta 1 positive area in the glomeruli and the elevation of mature TGF-beta 1 level in the renal cortex of nephrectomized rats. In the TJ-8117 treated group, activities of metalloproteinase 1, 2 or 9 in the renal cortex were elevated compared with the control group. Captopril failed to affect the TGF-beta 1 level. We also found that the constitutive herbs in TJ-8117, Rhei Rhizoma and Ginseng radix, inhibited the process from inactive TGF-beta 1 to mature TGF-beta 1.