Aims: In order to clarify the antinephritic mechanisms of saireito, the glucocorticoid receptor agonistic effect of saireito was evaluated in adrenalectomized rats with anti-glomerular basement membrane (anti-GBM) nephritis.
Methods: Rats with anti-GBM nephritis were subjected to adrenalectomy to exclude the effects of endogenous steroid hormones to investigate effects of saireito on the nephritis. The suppressive effects of saireito and saikosaponin D on the production of cytokines were investigated in vitro andin vivo.
Results: Administration of saireito or saikosaponin D significantly suppressed the increase of urinary protein excretion and histopathological changes in adrenalectomized nephritic rats. Coadministration of saireito or saikosaponin D and RU-38486, a glucocorticoid receptor antagonist, did not suppress the increase of urinary protein excretion. Saikosaponin D inhibited the glucocorticoid receptor binding of [(3)H]dexamethasone in anin vitro assay (IC(50) ratio 5.8 micromol/l). The IC(50) values of saikosaponin D for the release of IL-2 and IL-10 were 13.4 and 12.3 micromol/l, respectively. Administration of saireito and saikosaponin D prevented an increase in IL-2 levels in the renal cortex of anti-GBM nephritic rats.
Conclusion: These results suggest that the antinephritic effects of saireito may be partly attributable to an agonistic action on the glucocorticoid receptor by saikosaponin D, a component of saireito.
Copyright 2008 S. Karger AG, Basel.