The influence of the iridoids aucubin, catalpol and harpagosid as well as their metabolites on innate immune function

Iridoids are secondary plant constituents that are produced in the terpenoid metabolic pathway and can be divided into three major groups: iridoid glycosides, secoiridoids and non-glycosidical iridoids. The iridoid glycosides aucubin, catalpol and harpagosid can be found in various plants like Plantago lanceolatae L., Verbascum densiflorum Bertol., and Harpagophytum procumbens DC. ex MEISN. which are all known to be immune modulators in traditional herbal medicine. Aim of this study was to determine which of the three above mentioned iridoid glycosides can be spliced into their aglycon and its respective sugar residue under physiological conditions and whether they influence TNF-α secretion in undifferentiated and differentiated THP-1 cells under inflammatory conditions. We found that only aucubin and catalpol could be hydrolysed with β-glucosidase whereas harpagosid required an alkaline hydrolysis at a pH above 11. Yet, only harpagosid and its cinnamic acid lacking derivate harpagid were able to significantly influence TNF-α secretion in differentiated THP-1 cells, with a reduction down to 57% for harpagosid and 37% for harpagid. Aucubin and catalpol had no effect whereas their β-glycosidically spliced metabolites induced TNF-α secretion up to 145% and 185%, respectively.