Phenylethanoid glycosides as a new macrophage-activating factor

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Acteoside, a phenylpropanoid glycoside, was found to induce cytokine production and adhesion molecule expression on macrophages or SV4O-transformed endothelial cells (GEN-T). On the other hand, acteoside showed cytotoxicity against various kinds of tumor cells. In this study we studied whether the pathway of signal transduction in cell activation and cell death was different or not. Acteoside produced hydrogen peroxide which was detected by scopletin method as early as 1 min after its addition into medium. Its hydrogen peroxide production was dependent on the amount of acteoside and was abolished by the pretreatment with catalase. When the relationship between the amount of produced hydrogen peroxide and the intensity of cytotoxicity against tumor cells was examined, cell death was induced with the amount of produced hydrogen peroxide. In addition catalase completely inhibited acteoside-induced cell death. In contrast, cell adhesion molecule expression on GEN-T cells by acteoside was not influenced by pretreatment with catalase, suggesting that hydrogen peroxide was not implicated in the signal transduction of GEN-T cell activation by acteoside. We so far considered reactive oxygen species, intracellular calcium and protein phosphorylation as second messenger of signal transduction elicited by acteoside, whereas acteoside-derived hydrogen peroxide, and phosphorylation mediated by hydrogen peroxide would be negated by the facts described above. The precise mechanism of signal transduction remains to be clarified in the future.