concanavalin-a and taraxasterol

Discovery of anti-inflammatory drugs that can suppress T lymphocyte activation and proliferation by inhibiting TCR/CD3 and IL-2/IL-2R signaling is still needed in clinic, though rapamycin and other related reagents have made great success. Taraxasterol (TAS) is an active ingredient of dandelion, an anti-inflammatory medicinal herb with low in vivo toxicity that has long been used in China. Yet the action mechanism of TAS on lymphocytes remains elusive. The anti-inflammatory effects of TAS were evaluated in C57BL/6 mouse primary lymphocytes stimulated with concanavalin A (Con A) in vitro and in mouse model of Con A-induced acute hepatitis in vivo. Our results showed that TAS significantly suppressed Con A-induced acute hepatitis in a mouse model, reducing the hepatic necrosis areas, the release of aminotransferases, and the production of IL-2 and other inflammatory cytokines. Supporting this, in vitro study also showed that TAS reduced the production of IL-2 and the expression of IL-2 receptor subunit α (CD25) upon the stimulation of Con A, which was likely mediated by suppressing NF-κB activation. The downstream pathways of IL-2/IL-2R signaling, including the activation of PI3K/PDK1/mTOR, STAT3 and STAT5, were also suppressed by TAS. Consistently, Con A-induced T cell proliferation was also inhibited by TAS in vitro. Our data indicate that TAS can suppress both T lymphocyte activation and cell proliferation by down-regulating IL-2 expression and its signaling pathway thereby ameliorating Con A-induced acute hepatitis, highlighting TAS as a potential drug candidate for treating inflammatory diseases including autoimmune hepatitis.

Topics: Animals; Anti-Inflammatory Agents; Cell Proliferation; Chemical and Drug Induced Liver Injury; Concanavalin A; Cytokines; Female; Interleukin-2; Liver; Mice, Inbred C57BL; Signal Transduction; Sterols; T-Lymphocytes; Triterpenes

Topics: Alanine Transaminase; Animals; Apoptosis; Aspartate Aminotransferases; bcl-2-Associated X Protein; Chemical and Drug Induced Liver Injury; Concanavalin A; Cytokines; Cytoprotection; Glutathione; Hepatocytes; Male; Malondialdehyde; Mice; Mice, Inbred ICR; Proto-Oncogene Proteins c-bcl-2; Signal Transduction; Sterols; Superoxide Dismutase; Taraxacum; Toll-Like Receptors; Transcription Factor RelA; Triterpenes; Tumor Necrosis Factor-alpha