Saireito and saikosaponin D prevent urinary protein excretion via glucocorticoid receptor in adrenalectomized WKY rats with heterologous-phase anti-GBM nephritis.
OBJECTIVE
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.


CONCLUSIONS
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.
Hattori
Tomohisa
T
Tsumura & Co., Central Research Laboratories and Ibaraki Plant, Ami-machi, Japan. hattori_tomohisa@mail.tsumura.co.jp
Nishimura
Hiroaki
H
Kase
Yoshio
Y
Takeda
Shuichi
S
D000315:Adrenalectomy; D000818:Animals; D019867:Anti-Glomerular Basement Membrane Disease / Q000378:metabolism; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines / Q000652:urine*; D004359:Drug Therapy, Combination; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D016753:Interleukin-10 / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D008297:Male; D009828:Oleanolic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives*; D051381:Rats; D011921:Rats, Inbred WKY; D011965:Receptors, Glucocorticoid / Q000276:immunology*; D012503:Saponins / Q000008:administration & dosage*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D007376:Interleukin-2; D011965:Receptors, Glucocorticoid; D012503:Saponins; C080903:sairei-to; D016753:Interleukin-10; D009828:Oleanolic Acid; C025759:saikosaponin D