Immune-suppressive activity of punicalagin via inhibition of NFAT activation.
Since T cell activation is central to the development of autoimmune diseases, we screened a natural product library comprising 1400 samples of medicinal herbal extracts, to identify compounds that suppress T cell activity. Punicalagin (PCG) isolated from the fruit of Punica granatum was identified as a potent immune suppressant, based on its inhibitory action on the activation of the nuclear factor of activated T cells (NFAT). PCG downregulated the mRNA and soluble protein expression of interleukin-2 from anti-CD3/anti-CD28-stimulated murine splenic CD4+ T cells and suppressed mixed leukocytes reaction (MLR) without exhibiting cytotoxicity to the cells. In vivo, the PCG treatment inhibited phorbol 12-myristate 13-acetate (PMA)-induced chronic ear edema in mice and decreased CD3+ T cell infiltration of the inflamed tissue. These results suggest that PCG could be a potential candidate for the therapeutics of various immune pathologies.
Lee
Sang-Ik
SI
Institute of Traditional Medicine and Bioscience, Daejeon University, Yongun-dong, Dong-gu, Daejeon 300-716, Republic of Korea.
Kim
Byoung-Soo
BS
Kim
Kyoung-Shin
KS
Lee
Samkeun
S
Shin
Kwang-Soo
KS
Lim
Jong-Soon
JS
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D004423:Ear; D004487:Edema / Q000139:chemically induced / Q000276:immunology; D006801:Humans; D047348:Hydrolyzable Tannins / Q000302:isolation & purification / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism; D019169:Jurkat Cells; D008213:Lymphocyte Activation / Q000187:drug effects; D007959:Lymphocyte Culture Test, Mixed; D029561:Lythraceae / Q000737:chemistry; D051379:Mice; D008815:Mice, Inbred Strains; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity
D047348:Hydrolyzable Tannins; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D050778:NFATC Transcription Factors; C115642:punicalagin; D013755:Tetradecanoylphorbol Acetate