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.
Hattori
Tomohisa
T
Tsumura and Co., Pharmacology Research Department, R&D Division, 3586 Yoshiwara, Ami-machi, Ibaraki 300-1192, Japan. hattori_tomohisa@mail.tsumura.co.jp
Maruyama
Hirofumi
H
Nishimura
Hiroaki
H
Nakai
Yoichiro
Y
Sakakibara
Iwao
I
Kase
Yoshio
Y
Takeda
Shuichi
S
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