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.