Effects of Saireito, a Japanese herbal medicine, on edema via antagonistic actions against aldosterone in anti-GBM nephritic rats.
BACKGROUND
In order to clarify the diuretic mechanisms of Saireito, a Japanese herbal medicine, the mineralcorticoid receptor antagonistic action of Saireito was evaluated in anti-glomerular basement membrane (GBM) nephritic rats.


METHODS
Anti-GBM nephritis was induced in rats by the intravenous, injection of anti-GBM serum, and test drugs were administered 5 days after the induction of nephritis. In addition, we also investigated aldosterone-loaded mice to clarify the effects of test drugs on aldosterone signal transduction. In an in vitro study, a mineralocorticoid receptor binding assay of the components of Saireito was performed.


RESULTS
Saireito and spironolactone inhibited the development of proteinuria and abdominal ascites in anti-GBM nephritic rats. Saireito and spironolactone increased the urine volume and decreased the abdominal saline content in aldosterone-loaded mice. Saikosaponin H, a component of Saireito, inhibited the receptor binding of aldosterone in the in vitro assay 50% inhibitory concentration ([IC(50)], 22 micromol/l). Saikosaponin H also inihibited the decrease in urine volume in aldosterone-loaded mice.


CONCLUSIONS
These results suggest that the diuretic action of Saireito may be partly due to an antagonistic action on the mineralocorticoid receptor, exerted by saikosaponin H.
Tsumura and Co., Pharmacology Research Department, R&D Division, 3586 Yoshiwara, Ami-machi, Ibaraki 300-1192, Japan. hattori_tomohisa@mail.tsumura.co.jp
Tomohisa
T
Hattori
Hirofumi
H
Maruyama
Hiroaki
H
Nishimura
Yoichiro
Y
Nakai
Iwao
I
Sakakibara
Yoshio
Y
Kase
Shuichi
S
Takeda
D000450:Aldosterone / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000627:therapeutic use; D000906:Antibodies / Q000378:metabolism; D001323:Autoantibodies; D002216:Captopril / Q000627:therapeutic use; D004232:Diuretics / Q000378:metabolism / Q000627:therapeutic use; D004365:Drugs, Chinese Herbal / Q000378:metabolism / Q000627:therapeutic use; D004487:Edema / Q000188:drug therapy*; D005665:Furosemide / Q000627:therapeutic use; D006801:Humans; D007564:Japan; D008297:Male; D051379:Mice; D009393:Nephritis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D009828:Oleanolic Acid / Q000031:analogs & derivatives / Q000737:chemistry / Q000627:therapeutic use; D011188:Potassium / Q000652:urine; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000378:metabolism; D012503:Saponins / Q000737:chemistry / Q000627:therapeutic use; D012964:Sodium / Q000652:urine; D013148:Spironolactone / Q000627:therapeutic use
D000806:Angiotensin-Converting Enzyme Inhibitors; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000906:Antibodies; D001323:Autoantibodies; D004232:Diuretics; D004365:Drugs, Chinese Herbal; D018161:Receptors, Mineralocorticoid; D012503:Saponins; C051951:antiglomerular basement membrane antibody; C080903:sairei-to; D013148:Spironolactone; D000450:Aldosterone; D009828:Oleanolic Acid; D005665:Furosemide; D002216:Captopril; D012964:Sodium; D011188:Potassium; C025759:saikosaponin D