sapogenins and Glomerulonephritis

The effects of traditional Chinese medicine (Sairei-to) on experimental glomerulonephritis induced in rats by monoclonal antibody (mAb) 1-22-3 injection was examined. The level of proteinuria in the Sairei-to-treated group was significantly lower than that in the PBS treated group. This suppressive effect was caused by the major component of Sairei-to, Syo-saiko-to but not by another component, Gorel-san. The suppressive effect of Syo-saiko-to was identified in its components (Bupleuri radix, Pinelliae tuber and Zingiberis rhizoma), but not in the other combined components (Ginseng radix and Zizyphi fructus). Further study revealed that the suppressive effects of the combined components were mainly derived from Bupleuri radix. It was demonstrated that the actual active ingredient is probably Saikosaponin-d. Light microscopy revealed that Sairei-to and its effective components suppressed the proliferation of mesangial cells and mesangial matrix expansion. Semiquantitative morphological studies of glomerular lesions on the eighth day showed that Syo-saiko-to and its combined components (Bupleuri radix, Zingiberis rhizoma and Pinelliae tuber) suppressed mesangial matrix expansion significantly compared with phosphate-buffered saline control groups (matrix score: 28.0 +/- 19.1 vs 102.3 +/- 14.1; 30.9 +/- 30.1 vs 102.3 +/- 14.1, P < 0.005, respectively). It was concluded that Saikosaponin-d, as well as Bupleuri radix, Syo-saiko-to and Sairei-to can suppress proteinuria and morphological changes in the rat glomerulonephritis model induced by mAb 1-22-3.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antibodies, Monoclonal; Blood Chemical Analysis; Drugs, Chinese Herbal; Female; Glomerulonephritis; Kidney; Oleanolic Acid; Proteinuria; Rats; Rats, Wistar; Sapogenins; Saponins

This study was designed to clarify the anti-nephritic effects of the saikosaponins that are contained in Bupleurum falcatum L. crude saikosaponin at 1.0 mg and 5.0 mg/kg, i.p. prevented urinary protein excretion and elevation of serum cholesterol content on the 10th day after the injection of anti-GBM serum. Moreover, crude saikosaponin at 1.0 mg and 5.0 mg/kg, i.p. significantly inhibited histopathological changes such as hypercellularity and adhesion. On the other hand, saikosaponin a (5.0 mg/kg, i.p.) and d (1.0 mg and 5.0 mg/kg, i.p.) also prevented urinary protein excretion, elevation of serum cholesterol content, and histopathological changes. In the second study, to clarify the anti-nephritic mechanisms of saikosaponins on this model, we investigated the effect of saikosaponins on platelet aggregation, release of corticosterone and reactive oxygen species scavengers activity. Crude saikosaponin and saikosaponin d significantly inhibited the increase in platelet aggregation, and saikosaponin d enhanced the serum and intra-adrenal corticosterone levels. Crude saikosaponin and saikosaponin a inhibited the decrease in activity of scavengers (SOD, catalase, glutathione peroxidase). These results indicate that saikosaponins were effective on this model, and anti-nephritic mechanisms of saikosaponins were party due to anti-platelet, corticosterone releasing and enhancing action on the activity of reactive oxygen species scavengers.

Topics: Animals; Cholesterol; Corticosterone; Free Radical Scavengers; Glomerulonephritis; Glutathione Peroxidase; Kidney; Male; Oleanolic Acid; Platelet Aggregation; Platelet Aggregation Inhibitors; Proteinuria; Rats; Rats, Inbred Strains; Sapogenins; Saponins; Superoxide Dismutase