These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Flavonoids inhibit tumor necrosis factor-alpha-induced up-regulation of intercellular adhesion molecule-1 (ICAM-1) in respiratory epithelial cells through activator protein-1 and nuclear factor-kappaB: structure-activity relationships.
    Author: Chen CC, Chow MP, Huang WC, Lin YC, Chang YJ.
    Journal: Mol Pharmacol; 2004 Sep; 66(3):683-93. PubMed ID: 15322261.
    Abstract:
    Intercellular adhesion molecule-1 (ICAM-1) has been implicated in the processes of inflammation and carcinogenesis. Flavonoids, which are polyphenolic compounds with a wide distribution throughout the plant kingdom, have potent anti-inflammatory properties. We investigated the effects of flavonols (kaempferol, quercetin, and myricetin) and flavones (flavone, chrysin, apigenin, luteolin, baicalein, and baicalin) on the tumor necrosis factor-alpha (TNF-alpha)-stimulated ICAM-1 expression. Among those flavonoids tested, kaempferol, chrysin, apigenin, and luteolin are active inhibitors of ICAM-1 expression. Additional experiments suggested that apigenin and luteolin were actively inhibiting the IkappaB kinase (IKK) activity, the IkappaBalpha degradation, the nuclear factor-kappaB (NF-kappaB) DNA-protein binding, and the NF-kappaB luciferase activity. TNF-alpha-induced ICAM-1 promoter activity was attenuated using an activator protein-1 (AP-1) site deletion mutant, indicating the involvement of AP-1 in ICAM-1 expression. AP-1-specific DNA-protein binding activity was increased by TNF-alpha, and the supershift assay identified the components of c-fos and c-jun. Extracellular signal-regulated kinase (ERK) and p38 were involved in the c-fos mRNA expression, and c-Jun NH(2)-terminal kinase (JNK) was involved in the c-jun mRNA expression. All three mitogen-activated protein kinase (MAPK) activities were inhibited by apigenin and luteolin. In comparison, kaempferol and chrysin only inhibited the JNK activity. The inhibitory effects of apigenin and luteolin on ICAM-1 expression are mediated by the sequential attenuation of the three MAPKs activities, the c-fos and c-jun mRNA expressions, and the AP-1 transcriptional activity. IKK/NF-kappaB pathway is also involved; however, kaempferol- and chrysin-mediated inhibitions are primarily executed through the attenuation of JNK activity, c-jun mRNA expression, and AP-1 activity. The structure-activity relationships are also explored, and the important role of -OH group at positions 5 and 7 of A ring and at position 4 of B ring is noted. Finally, our results suggested that AP-1 seems to play a more significant role than NF-kappaB in the flavonoid-induced ICAM-1 inhibition.
    [Abstract] [Full Text] [Related] [New Search]