Synergistic immunosuppressive effects of rosmarinic acid and rapamycin in vitro and in vivo.
BACKGROUND
We previously demonstrated that rosmarinic acid (RosA) inhibits T-cell antigen receptor-induced T-cell activation and proliferation. In this study, we evaluated the ability of RosA alone and in conjunction with currently used immunosuppressive drugs to inhibit in vitro splenic T-cell proliferation and prolong skin graft survival in vivo.


METHODS
Mouse splenic T-cell proliferation assays were performed in the presence of RosA alone or in combination with cyclosporine, rapamycin (Rapa), or prednisone (Pred). The in vivo synergistic efficacy of RosA and Rapa was evaluated in the mouse skin allograft model.


RESULTS
RosA combined with Rapa or prednisone synergistically inhibited splenic T-cell proliferation, whereas the combination of RosA and cyclosporine additively inhibited T-cell proliferation. The combination of RosA and Rapa synergistically prolonged allograft survival.


CONCLUSIONS
We conclude that the combination of RosA and Rapa promotes immunosuppressive effects.
Yun
Su-Young
SY
Signal Transduction Laboratory, Mogam Biotechnology Research Institute, Gyonggido, Korea.
Hur
Yun-Gyoung
YG
Kang
Mi-Ae
MA
Lee
Jihyun
J
Ahn
Curie
C
Won
Jonghwa
J
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology; D053630:Depsides; D004357:Drug Synergism; D005938:Glucocorticoids / Q000494:pharmacology; D006085:Graft Survival / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011241:Prednisone / Q000494:pharmacology; D020123:Sirolimus / Q000494:pharmacology*; D016038:Skin Transplantation; D013154:Spleen / Q000166:cytology*; D013601:T-Lymphocytes / Q000166:cytology; D000097123:Rosmarinic Acid
D002934:Cinnamates; D016572:Cyclosporine; D053630:Depsides; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D011241:Prednisone; D020123:Sirolimus; D000097123:Rosmarinic Acid