Impact of allicin on macrophage activity

Allicin (diallyl thiosulphinate) is the main antimicrobial constituent of garlic. It has been suggested for use as an antibiotic, or for treating diseases such as cancer and diabetes. Yet, several lines of evidence indicate that allicin affects cells of the immune system. Therefore, this study investigates its impact on macrophages, using the murine Raw 264.7 cell line. Half-maximal allicin toxicity occurred around 130 μM in Raw cells, which was comparable to values in Escherichia coli. Furthermore, allicin inhibited nitrogen monoxide production by the inducible nitric oxide synthase (iNOS), whereas it had no impact on the oxidative burst. Moreover, a reporter gene assay indicated activation of the promoter for the pro-inflammatory cytokine TNF-α, although, at higher concentrations than those required for iNOS inhibition. Investigating the molecular basis for the activation by allicin, we found that it triggered zinc, but not calcium signals, and inhibited dephosphorylation of the mitogen activated protein kinase, ERK1/2. Both effects were possibly caused by oxidizing cysteine thiols. In conclusion, whereas allicin might not be a promising antibiotic, it has a potential use for selectively suppressing iNOS expression in macrophages.