Synergistic immunosuppressive effects of rosmarinic acid and rapamycin in vitro and in vivo

Transplantation. 2003 May 27;75(10):1758-60. doi: 10.1097/01.TP.0000063933.12440.50.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / drug effects
  • Cinnamates / pharmacology*
  • Cyclosporine / pharmacology
  • Depsides
  • Drug Synergism
  • Glucocorticoids / pharmacology
  • Graft Survival / drug effects
  • Immunosuppressive Agents / pharmacology*
  • In Vitro Techniques
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Prednisone / pharmacology
  • Rosmarinic Acid
  • Sirolimus / pharmacology*
  • Skin Transplantation
  • Spleen / cytology*
  • T-Lymphocytes / cytology

Substances

  • Cinnamates
  • Depsides
  • Glucocorticoids
  • Immunosuppressive Agents
  • Cyclosporine
  • Prednisone
  • Sirolimus