[Effects of onpi-to (TJ-8117) and (-)epicatechin-3-O-gallate on the proliferating changes in glomeruli of 5/6 nephrectomized rats].

Onpi-to (TJ-8117) is a herbal medicine composed of five crude drugs (Rhei Rhizoma, Glycyrrhizae Radix, Ginseng Radix, Zingiberis Rhizoma and Aconiti Tuber). Our previous experiments have demonstrated that TJ-8117 suppressed the development of glomerulosclerosis and retarded the deterioration of renal function in 5/6 nephrectomised rats. In the present study, the effects of TJ-8117 and (-)Epicatechin-3-O-gallate (ECG), which is a component of Rhei Rhizoma, on glomerular cell proliferation, extracellular matrix accumulation and glomerular hypertrophy were investigated in 5/6 nephrectomized rats. Male Wistar rats (170-180 g) were subjected to 5/6 nephrectomy, and TJ-8117 (0.32%, 0.64%) or angiotensin-converting enzyme inhibitor, captopril (CAP 0.08%) was administered daily by mixing in normal chow and ECG (2 mg, 8 mg/100 ml) by drinking water from the day after 5/6 nephrectomy. Following 5/6 nephrectomy, glomerular cell poliferation was increased and reached a maximum at 1 week in the untreated control rats, but was suppressed significantly at 1 and 2 weeks after treatment with TJ-8117 and at only 1 week after treatment with CAP. Extracellular matrix accumulation was detected after 1 week and increased gradually until 4 weeks in the control rats, whereas it was significantly inhibited in both the TJ-8117- and CAP-treated rats. In addition, immunohistochemistry revealed that TJ-8117 significantly inhibited the increase of fibronectin, and tended to reduce type I and type IV collagen at 4 weeks. Furthermore, TJ-8117 suppressed glomerular hypertrophy at 4 weeks. Systolic blood pressure (SBP) and urinary protein excretion (UP) were higher in the control rats than sham-operated rats. TJ-8117 prevented this increase of SBP and UP at 1 week. ECG also suppressed glomerular cell proliferation and the increase of SBP and UP at 1 week after 5/6 nephrectomy. These findings suggest that ECG was one of active components of TJ-8117. These results suggest that TJ-8117 suppressed proliferating changes in glomeruli at an early stage in 5/6 nephrectomized rats, and inhibited the development of glomerulosclerosis.