Combination of Paeoniae Radix and Cnidii Rhizoma Prolonged Survival of Fully Mismatched Cardiac Allografts and Generated Regulatory Cells in Mice

Abstract EN

In previous studies, we have demonstrated that Tokishakuyakusan (TJ-23) can prolong the survival of allogeneic cardiac grafts and induce regulatory T cells.

In this study we investigated the effects of Paeoniae radix and Cnidii rhizoma, two components of TJ-23, on alloimmune responses in a murine cardiac transplantation model and whether the two agents have synergistic effect.

CBA mice underwent transplantation of a C57BL/6 heart and received oral administration of 2 g/kg/day of Paeoniae radix, Cnidii rhizoma, or the mixture of two agents from the day of transplantation until 7 days afterward.

Naïve CBA mice rejected C57BL/6 cardiac graft acutely (median survival time (MST): 7 days).

Paeoniae radix and Cnidii rhizoma prolonged C57BL/6 allograft survival (MSTs: 13.5 and 15.5 days, resp.).

However, the mixture of two agents prolonged C57BL/6 allograft survival indefinitely (MST > 100 days).

Secondary CBA recipients given whole splenocytes from primary combination-treated CBA recipients with B6 cardiac allografts 30 days after grafting had prolonged survival of B6 hearts (MST: 33 days).

Flow cytometry studies showed that the CD4+CD25+Foxp3+ regulatory cell population was increased in combination-treated recipients.

Combination of Paeoniae radix and Cnidii rhizoma induced hyporesponsiveness to fully allogeneic cardiac allografts and may generate CD4+CD25+Foxp3+ regulatory cells in our model.