Saireito Induced Prolonged Survival of Fully Mismatched Cardiac Allografts in Mice / 日本東洋医学雑誌

ABSTRACT

Saireito, a 12-component Japanese herbal medicine, is used to treat immune-related diseases. We investigated the effects of oral administration of Saireito extract in a murine model of cardiac transplantation with fully mismatched allografts. Untreated recipients and those given water rejected their cardiac allografts acutely (median survival time [MST], 7 and 8 days, respectively), as did those treated with either 0.02 or 0.002 g/kg/day of Saireito extract (MST, 7 days in both groups). Recipients given 0.2 g/kg/day of Saireito extract had only moderate prolongation of allograft survival (MST, 41 days). However, all transplant recipients given 2 g/kg/day of Saireito extract had significant prolongation of allograft survival (MST>100 days). None of the single crude drug extracts of Saireito prolonged allograft survival, suggesting that its effects require administration of the combination agent. In mixed leukocyte cultures, proliferation of splenocytes from Saireito-treated CBA recipients was markedly suppressed compared with that of splenocytes from untreated mice, and interferon-γ production was significantly reduced. In flow cytometry experiment, the population of CD 4+CD 25+FOXP 3+cells was increased in the spleens of Saireito-treated CBA recipients compared with the spleens of naïve CBA mice or untreated CBA recipients. Thus, in our model, Saireito treatment induced hyporesponsiveness to cardiac allografts in a dose-dependent manner, and the combination of the components is essential for this effect.