Dimeric procyanidins are inhibitors of NF-kappaB-DNA binding.
Given the central role of the transcription factor NF-kappaB in inflammation, molecules that can inhibit NF-kappaB are being actively investigated. The present work characterize potential interactions between dimeric procyanidins [B-type (B1 and B2) and A-type (A1 and A2)] and NF-kappaB proteins. B1 and B2, inhibited tumor necrosis factor alpha (TNFalpha)- and phorbol 12-myristate 13-acetate (PMA)-induced transactivation of NF-kappaB-driven genes and the increase of NF-kappaB-DNA nuclear binding in Jurkat T cells. B1 and B2, added in vitro to nuclear fractions, inhibited NF-kappaB binding to its DNA consensus sequence. B1 and B2 prevented the binding of RelA and p50 recombinant proteins to its DNA consensus sequence. All these effects were not observed with A1 and A2. Putative molecular models for possible interactions of B1, B2, A1 and A2, with NF-kappaB proteins were constructed, indicating that B-type dimeric procyanidins have higher possibilities of chemical interactions with NF-kappaB than A-type dimeric procyanidins. The results support the concept that B-type dimeric procyanidins can provide anti-inflammatory benefits due to their ability to reduce NF-kappaB binding to the DNA.
Mackenzie
Gerardo G
GG
Department of Nutrition, University of California-Davis, One Shields Avenue, Davis, CA 95616, USA.
Delfino
Jose M
JM
Keen
Carl L
CL
Fraga
Cesar G
CG
Oteiza
Patricia I
PI
D004247:DNA / Q000378:metabolism*; D019281:Dimerization; D024202:Electrophoretic Mobility Shift Assay; D006801:Humans; D019169:Jurkat Cells; D008958:Models, Molecular; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D044945:Proanthocyanidins / Q000737:chemistry / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000494:pharmacology
D016328:NF-kappa B; D044945:Proanthocyanidins; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D013755:Tetradecanoylphorbol Acetate