title: The influence of harpagoside and harpagide on TNFα-secretion and cell adhesion molecule mRNA-expression in IFNγ/LPS-stimulated THP-1 cells.
abstract: 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 3h and expression could be maintained on high levels even after 48h. L-selectin and PSGL-1 were strongly induced after 48h 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.
authors.affiliation: Freie Universität Berlin, Fachbereich für Pharmazie, Königin-Luise-Straße 2+4, 14195 Berlin, Germany. Electronic address: pschopohl@uni-potsdam.de.
authors.forename: P
authors.initials: P
authors.lastname: Schopohl
authors.affiliation: Freie Universität Berlin, Fachbereich für Pharmazie, Königin-Luise-Straße 2+4, 14195 Berlin, Germany. Electronic address: paul.grueneberg@gmail.com.
authors.forename: P
authors.initials: P
authors.lastname: Grüneberg
authors.affiliation: Freie Universität Berlin, Fachbereich für Pharmazie, Königin-Luise-Straße 2+4, 14195 Berlin, Germany. Electronic address: melzig@zedat.fu-berlin.de.
authors.forename: M F
authors.initials: MF
authors.lastname: Melzig
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry*; D002454:Cell Differentiation; D002460:Cell Line; D002465:Cell Movement; D006027:Glycosides / Q000737:chemistry*; D031684:Harpagophytum / Q000737:chemistry; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma; D057889:Iridoid Glycosides / Q000737:chemistry*; D019041:L-Selectin / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects*; D010946:Plants, Medicinal / Q000737:chemistry; D011714:Pyrans / Q000737:chemistry*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D006027:Glycosides; D057889:Iridoid Glycosides; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D011714:Pyrans; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D007371:Interferon-gamma; C033249:harpagoside; C033250:harpagide
keywords: Adhesion; FSL-1; FSL-1 (PubChem CID: 87858248); Harpagide; Harpagide (PubChem CID: 10044294); Harpagoside; Harpagoside (PubChem CID: 5281542); LPS; Lipopolysaccharide (PubChem ID: 11970143); Migration; Phorbol 12-myristate 13-acetate (PubChem CID: 27924)