Kaempferol from Semen cuscutae attenuates the immune function of dendritic cells.

Dendritic cells (DCs) are the critical leukocytes in regulating immune responses. Accordingly, DCs are the major target in the development of immunomodulators. In this study, we examined the effect of Semen cuscutae (SC), an important traditional Chinese medicine, on mouse bone marrow-derived DCs. We found that the n-butanol and methanol extracts of SC significantly suppressed LPS-stimulated DC activation. Several flavonoids were verified in the extracts using HPLC, and then kaempferol was identified as the major flavonoid in the methanol fraction of SC. Kaempferol was able to reduce cytokines and chemokines produced by LPS-stimulated DCs, and this reduction was not due to its cytotoxicity on DCs. In addition, DC maturation was impaired by kaempferol. Furthermore, kaempferol abrogated the ability of LPS-stimulated DCs to promote Ag-specific T cell activation, both in vitro and in vivo. Thus, we show for the first time that SC exhibits an immunosuppressive effect on DCs and that the active ingredient kaempferol attenuates DC function, which suggests that kaempferol has potential in the treatment of chronic inflammatory and autoimmune diseases.

A novel adjuvant Ling Zhi-8 enhances the efficacy of DNA cancer vaccine by activating dendritic cells.

DNA vaccine has been suggested to use in cancer therapy, but the efficacy remains to be improved. The immunostimulatory effect of a fungal immunomodulatory protein Ling Zhi-8 (LZ-8) isolated from Ganoderma lucidum has been reported. In this study, we tested the adjuvanticity of LZ-8 for HER-2/neu DNA vaccine against p185(neu) expressing tumor MBT-2 in mice. We found that recombinant LZ-8 stimulated mouse bone marrow-derived dendritic cells (DCs) via TLR4 and its stimulatory effect was not due to any microbe contaminant. In addition, LZ-8 enhanced the ability of DCs to induce antigen-specific T cell activation in vitro and in a subunit vaccine model in vivo. Surprisingly, LZ-8 cotreatment strongly improved the therapeutic effect of DNA vaccine against MBT-2 tumor in mice. This increase in antitumor activity was attributed to the enhancement of vaccine-induced Th1 and CTL responses. Consistent with the results from DCs, the promoting effect of LZ-8 on DNA vaccine was diminished when the MBT-2 tumor cells were grown in TLR4 mutant mice. Thus, we concluded that LZ-8 may be a promising adjuvant to enhance the efficacy of DNA vaccine by activating DCs via TLR4.