Research: ZHOU and COLLEAGUES,

Listed in Issue 197

Abstract

ZHOU and COLLEAGUES, Department of Immunology, H. Lee. Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA studied the effect of ICT, the major active ingredient of Herba Epimedii, upon the anti-inflammatory and anti-tumour effects in myeloid derived suppressive cells functions.

Background

3, 5,7-trihydroxy-4'-methoxy-8-(3-hydroxy-3-methylbutyl)-flavone (ICT) is a novel derivative of Icariin (ICA), the major active ingredient of Herba Epimedii, a herb used in traditional Chinese and alternative medicine.

Methodology

We previously demonstrated its anti-inflammatory effect in murine innate immune cells and activated human PBMCs.

Results

We report herein that ICA or ICT treatment reduces the expression of MRP8/MRP14 and toll-like receptor 4 (TLR4) on human PBMCs. Administration of ICA or ICT inhibited tumour growth in 4T1-Neu tumour-bearing mice and considerably decreased MDSC numbers in the spleen of these mice. Further, we saw a restoration of IFN-gamma production by CD8+ T cells in tumour bearing mice when treated with ICA or ICT. ICA and ICT significantly decreased the amounts of nitric oxide and reactive oxygen species in MDSC in vivo. When MDSC were treated in vitro with ICT, we saw a significant reduction in the percent of these cells with concomitant differentiation into dendritic cells and macrophages. Concomitant with this cell type conversion was a down-regulation of IL-10, IL-6 and TNF-alpha production. Decreased expression of S100A8/9 and inhibition of activation of STAT3 and AKT may in part be responsible for the observed results.

Conclusion

In conclusion, our results showed that ICA, and more robustly, ICT, directly modulate MDSC signalling and therefore altered the phenotype and function of these cells, in vitro and in vivo.

References

Zhou J, Wu J, Chen X, Fortenbery N, Eksioglu E, Kodumudi KN, Pk EB, Dong J, Djeu JY and Wei S. Icariin and its derivative, ICT, exert anti-inflammatory, anti-tumor effects, and modulate myeloid derived suppressive cells (MDSCs) functions. International Immunopharmacology. 11(7):890-8, Jul 2011. Other ID Source: NLM. NIHMS265001 [Available on 07/01/12] Source: NLM. PMC3109231 [Available on 07/01/12].

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