Abstract
Andrographolide (1), an active constituent of Andrographis paniculata, decreased tumor necrosis factor-α (TNF-α)-induced intercellular adhesion molecule-1 (ICAM-1) expression and adhesion of HL-60 cells onto human umbilical vein endothelial cells (HUVEC), which are associated with inflammatory diseases. Moreover, 1 abolished TNF-α-induced Akt phosphorylation. Transfection of an activated Akt1 cDNA vector increased Akt phosphorylation and ICAM-1 expression like TNF-α. In addition, 1 and LY294002 blocked TNF-α-induced IκB-α degradation and nuclear p65 protein accumulation, as well as the DNA-binding activity of NF-κB. Compound 1 exhibits anti-inflammatory properties through the inhibition of TNF-α-induced ICAM-1 expression. The anti-inflammatory activity of 1 may be associated with the inhibition of the PI3K/Akt pathway and downstream target NF-κB activation in HUVEC cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
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Cell Survival / drug effects
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Chromones / pharmacology*
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DNA / drug effects
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DNA / metabolism
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Diterpenes / chemistry
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Diterpenes / pharmacology*
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Down-Regulation
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HL-60 Cells
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Human Umbilical Vein Endothelial Cells / drug effects*
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Humans
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Intercellular Adhesion Molecule-1 / drug effects
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / metabolism
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Molecular Structure
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Morpholines / pharmacology*
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NF-kappa B / drug effects
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NF-kappa B / metabolism*
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Proto-Oncogene Proteins c-akt / metabolism*
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Tumor Necrosis Factor-alpha / antagonists & inhibitors*
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Chromones
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Diterpenes
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Morpholines
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NF-kappa B
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Tumor Necrosis Factor-alpha
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Intercellular Adhesion Molecule-1
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2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
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andrographolide
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DNA
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Proto-Oncogene Proteins c-akt