Blocking effect of an immuno-suppressive agent, cynarin, on CD28 of T-cell receptor

  • Pharm Res. 2009 Feb;26(2):375-81. doi: 10.1007/s11095-008-9754-5.
Guo-Chung Dong  1 ,  Ping-Hsien Chuang ,  Kai-chun Chang ,  Pey-shynan Jan ,  Pei-Ing Hwang ,  Huan-Bin Wu ,  Myunggi Yi ,  Huan-Xiang Zhou ,  Hueih Min Chen
Affiliations
  • 1. Agricultural Biotechnology Research Center, Academia Sinica, Taipei, 115, Taiwan.
PMID: 18989760 DOI: 10.1007/s11095-008-9754-5
Abstract

Purpose: Cynarin, a potential immunosuppressant that blocks the interaction between the CD28 of T-cell receptor and CD80 of antigen presenting cells, was found in Echinacea purpurea by a new pharmaceutical screening method: After Flowing Through Immobilized Receptor (AFTIR; Dong et al., J Med Chem, 49: 1845-1854, 2006). This Echinacea component is the first small molecule that is able to specifically block "signal 2" of T-cell activation.

Methods: In this study, we used the AFTIR method to further confirm that cynarin effectively blocked the binding between CD80 of B-cells and CD28 of T-cells, and provide details of its mechanism of action.

Results: The experimental results showed that cynarin blocked about 87% of the CD28-dependent "signal 2" pathway of T-cell activation under the condition of one to one ratio of T-cell and B-cell in vitro. Theoretical structure modeling showed that cynarin binds to the "G-pocket" of CD28 (Evans et al., Nat Immunol, 6:271-279, 2005), and thus interrupts the site of interaction between CD28 and CD80.

Conclusions: These results confirm both that AFTIR is a promising method for screening selective active compounds from herbal medicine and that cynarin has great potential as an immuno-suppressive agent.

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