title: CML-1 inhibits TNF-alpha-induced NF-kappaB activation and adhesion molecule expression in endothelial cells through inhibition of IkBalpha kinase.
abstract: CML-1 is a purified extract from a mixture of 13 oriental herbs (Achyranthis Radix, Angelicae Gigantis Radix, Cinnamomi Cortex Spissus, Eucommiae Cortex, Glycyrrhizae Radix, Hoelen, Lycii Fructus, Paeoniae Radix, Rehmanniae Radix Preparata and Atractylodis Rhizoma, Zingiberis Rhizoma, Zizyphi Semen, Acori Graminei Rhizoma) that have been widely used for the treatment of inflammatory diseases in Asia. Since our previous study has been shown to have the anti-inflammatory activity of CML-1 in vivo and the upregulation of adhesion molecules in response to numerous inducing factors is associated with inflammation, this study examined the effect of CML-1 on the expression of adhesion molecules induced by TNF-alpha in cultured human umbilical vein endothelial cells (HUVECs). Preincubation of HUVECs for 20h with CML-1 (1-100mug/ml) dose-dependently inhibited TNF-alpha (10ng/ml)-induced adhesion of THP-1 monocytic cells, as well as mRNA and protein expression of E-selectin, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1). CML-1 was also shown to inhibit NK-kB activation induced by TNF-alpha. Furthermore, CML-1 inhibited TNF-alpha-induced IkB kinase activation, subsequent degradation of IkBalpha, and nuclear translocation of NK-kB. Evidence presented in this report demonstrated that CML-1 inhibited the adhesive capacity of HUVEC and the TNF-alpha-mediated induction of E-selectin, ICAM-1 and VCAM-1 in HUVEC by inhibiting the IkB/NF-kB signaling pathway at the level of IkB kinase, which may explain the ability of CML-1 to suppress inflammation and modulate the immune response.
authors.affiliation: College of Pharmacy, Sungkyunkwan University, Suwon City, Kyunggi-do 440-746, Republic of Korea.
authors.forename: Seong-Ji
authors.initials: SJ
authors.lastname: Mo
authors.forename: Eun-Wha
authors.initials: EW
authors.lastname: Son
authors.forename: Sung-Ryul
authors.initials: SR
authors.lastname: Lee
authors.forename: Sun-Mee
authors.initials: SM
authors.lastname: Lee
authors.forename: Dae-Hee
authors.initials: DH
authors.lastname: Shin
authors.forename: Suhkneung
authors.initials: S
authors.lastname: Pyo
mesh_terms: D001711:Biotransformation / Q000187:drug effects; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000096:biosynthesis*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D019040:E-Selectin / Q000096:biosynthesis; D024202:Electrophoretic Mobility Shift Assay; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D051550:I-kappa B Kinase / Q000037:antagonists & inhibitors*; D047468:Immunoprecipitation; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016328:NF-kappa B / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: C518724:CML-1 plant extract; D015815:Cell Adhesion Molecules; D019040:E-Selectin; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D051550:I-kappa B Kinase