Tokishakuyakusan Induces Prolonged Survival of Fully Mismatched Cardiac Allografts and Generates Regulatory Cells in Mice / 日本東洋医学雑誌

ABSTRACT

Tokishakuyakusan is a Japanese herbal medicine which is extracts from six herbal materials. The author investigated the effects of oral administration of Tokishakuyakusan in a murine model of cardiac transplantation with fully mismatched allografts. CBA mice (H 2k) underwent transplantation of C 57 BL/6 (H 2b) hearts and received oral administration of Tokishakuyakusan from day 0 to day 7 after grafting. Untreated CBA mice rejected C 57 BL/6 cardiac grafts acutely (median survival time [MST], 7 days). Mice given 2 g/kg/day of Tokishakuyakusan accepted their grafts (MST, 60 days). However, each herbal material alone and 0.2, 0.02 g/kg/day of Tokishakuyakusan did not prolong the allografts survival. Splenocytes from Tokishakuyakusan-treated recipients showed alloproliferative hyporesponsiveness and down-regulation of IFN-γ in mixed leukocyte culture with C 57 BL/6 stimulators. Secondary CBA recipients (naive) given whole splenocytes from primary Tokishakuyakusan-treated CBA recipients with C 57 BL/6 cardiac allografts 30 days after grafting had prolonged survival of C 57 BL/6 hearts (MST, 100 days) compared to that in the secondary recipients with adoptive transfer of naive splenocytes (MST, 12 days). In flow cytometry experiment, the population of CD 4+CD 25+cells, CD 4+FOXP 3+cells and CD 25+FOXP 3+cells were increased in the spleens of Tokishakuyaku-san-treated CBA recipients. Treatment with Tokishakuyakusan induced unresponsiveness to fully allogeneic cardiac allograft and generated regulatory cells. Traditional knowledge of Japanese herbal medicine may contribute to immunomodulation after modern transplantation surgery.