The influence of harpagoside and harpagide on TNFα-secretion and cell adhesion molecule mRNA-expression in IFNγ/LPS-stimulated THP-1 cells

- Cell viability of PMA-differentiated THP-1 cells was influenced by neither harpagoside nor harpagide.
- Both iridoids, harpagoside and harpagide, had an inhibitory effect on IFNγ/LPS induced TNFα-secretion.
- In undifferentiated THP-1 cells harpagoside and harpagide had almost no effect on TNFα-secretion.
- The expression of various cell adhesion molecules like ICAM-1 and L-selectin was significantly induced.

Inflammation does not only lead to pain and functio laesa in the affected tissue but is also implicated in the onset and progression of cardiovascular diseases and cancer. Many medicinal plants show anti-inflammatory properties yet plant-constituents and their effect on molecular pathways involved in the attenuation of inflammation as well as cell migration are only poorly understood. Harpagophytum procumbens DC. ex MEISN. is a potent plant used as an immune modulator in traditional herbal medicine. Aim of this study was to investigate the influence of harpagoside and harpagide on TNFα-secretion in undifferentiated and differentiated THP-1 cells under inflammatory conditions as well as their implication in cellular migration into inflamed tissue. We found that both iridoids decrease TNFα-secretion in PMA-differentiated THP-1 cells whereas undifferentiated cells were poorly affected. Yet, in undifferentiated cells harpagoside and harpagide induced mRNA-expression of certain proteins involved in leukocyte transmigration. Especially TNFα and ICAM-1 mRNA-expression was positively affected after 3 h and expression could be maintained on high levels even after 48 h. L-selectin and PSGL-1 were strongly induced after 48 h of stimulation. This ambiguous effect of harpagoside and harpagide highlights their immune modulatory function by facilitating cell migration into the inflamed tissue, whereby in consequence the anti-inflammatory activity of the resident macrophages was also found to be promoted.

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