title: Ginsenoside metabolite compound K differentially antagonizing tumor necrosis factor-α-induced monocyte-endothelial trafficking.
abstract: Human leukocyte endothelial adhesion and transmigration occur in the early stage of the pathogenesis of atherosclerosis. Vascular endothelial cells are targeted by pro-inflammatory cytokines modulating many gene proteins responsible for cell adhesion, thrombosis and inflammatory responses. This study examined the potential of compound K to inhibit the pro-inflammatory cytokine TNF-α induction of monocyte adhesion onto TNF-α-activated human umbilical vein endothelial cells (HUVEC). HUVEC were cultured with 10ng/ml TNF-α with individual ginsenosides of Rb1, Rc, Re, Rh1 and compound K (CK). Ginsenosides at doses of ⩽50μM did not show any cytotoxicity. TNF-α induced THP-1 monocyte adhesion to HUVEC, and such induction was attenuated by Rh1 and CK. Consistently, CK suppressed TNF-α-induced expression of HUVEC adhesion molecules of VCAM-1, ICAM-1 and E-selectin, and also Rh1 showed a substantial inhibition. Rh1 and CK dampened induction of counter-receptors, α4/β1 integrin VLA-4 and αL/β2 integrin LFA-1 in TNF-α-treated THP-1 cells. Additionally, CK diminished THP-1 secretion of MMP-9 required during transmigration, inhibiting transendothelial migration of THP-1 cells. CK blunted TNF-α-promoted IL-8 secretion of HUVEC and CXCR1 expression of THP-1 monocytes. Furthermore, TNF-α-activated endothelial IκB phosphorylation and NF-κB nuclear translocation were disturbed by CK, and TNF-α induction of α4/β1 integrin was abrogated by the NF-κB inhibitor SN50. These results demonstrate that CK exerts anti-atherogenic activity with blocking leukocyte endothelial interaction and transmigration through negatively mediating NF-κB signaling.
authors.affiliation: Department of Food and Nutrition and the Regional Research Universities Program/Medical & Bio-Materials Research Center, Hallym University, Chuncheon, Kangwon-do, Republic of Korea.
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Lee
authors.forename: Jung-Suk
authors.initials: JS
authors.lastname: Choi
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Kim
authors.forename: Hyun Ju
authors.initials: HJ
authors.lastname: You
authors.forename: Geun Eog
authors.initials: GE
authors.lastname: Ji
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Kang
mesh_terms: D002448:Cell Adhesion / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D007948:Leukemia, Monocytic, Acute / Q000378:metabolism / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D036145:Ginsenosides; D020780:Matrix Metalloproteinase 9; D014409:Tumor Necrosis Factor-alpha; C112772:ginsenoside compound K