[Sairei-to inhibits the production of endothelin-1 by nephritic glomeruli(2): alisols, possible candidates as active compounds].
We have previously reported that Sairei-to (TJ-114), a Japanese herbal medicine, prevented the production of endothelin-1 in anti-GBM nephritic rats, and that Alismatis Rhizoma (Takusha in Japanese), one of the twelve herbs composing TJ-114, might be responsible for the action. In order to further clarify the antinephritic components of TJ-114, we investigated the effects of Takusha extracts on various parameters, including endothelin-1 production of glomeruli in vitro and in vivo using anti-GBM nephritic rats. MeOH-100% MeOH and MeOH-50% MeOH fractions (31.3 microgram/ml or higher) strongly inhibited an increase in endothelin-1 concentration in culture medium when they were added to a culture of glomerular cells derived from nephritic rats. In addition, oral administration of the MeOH-100% MeOH fraction (30 mg/kg) ameliorated the proteinuria, increase in systolic blood pressure and changes in histopathological parameters in nephritic rats. Oral administration of the MeOH-100% MeOH fraction inhibited increase in endothelin-1 expression in the glomeruli of nephritic rats and in endothelin-1 production by a culture of glomerular cells derived from the nephritic rats. Alisols A and B, the main constituents of the MeOH-100% MeOH fraction, inhibited in vitro endothelin-1 production by glomerular cells derived from the nephritic rats. Oral administration of alisol B (30 mg/kg) prevented the endothelin-1 expression by glomeruli and the increase in endothelin-1 production by cultured nephritic glomerular cells. Oral administration of alisol B also ameliorated the proteinuria, the increase in systolic blood pressure and the changes in histopathological parameters in the nephritic rats. These results indicate that the antinephritic action of TJ-114, resulting from the inhibition of endothelin-1 production, may be attributed to the alisols in Takusha.
Hattori
T
T
New Drug Research Department, TSUMURA & Co. Central Laboratories, Ibaragi, Japan.
Nishimura
H
H
Makino
B
B
Shindo
S
S
Kawamura
H
H
D000818:Animals; D002478:Cells, Cultured; D003864:Depression, Chemical; D004365:Drugs, Chinese Herbal / Q000494:pharmacology* / Q000627:therapeutic use; D019332:Endothelin-1 / Q000096:biosynthesis*; D005921:Glomerulonephritis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D007678:Kidney Glomerulus / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
D004365:Drugs, Chinese Herbal; D019332:Endothelin-1; C080903:sairei-to