1 research outputs found
Inhibition of NF-κB-Dependent Cytokine and Inducible Nitric Oxide Synthesis by the Macrocyclic Ellagitannin Oenothein B in TLR-Stimulated RAW 264.7 Macrophages
Immunomodulatory effects of oenothein B (<b>1</b>), a macrocyclic
ellagitannin from various Onagraceae species, have been described
previously. However, the mechanisms underlying the anti-inflammatory
activity of <b>1</b> have not been fully clarified. The effects
of <b>1</b> were investigated on inducible nitric oxide synthase,
TLR-dependent and TLR-independent signal transduction cascades, and
cytokine expression using murine macrophages (RAW 264.7). Compound <b>1</b> (10–60 μg/mL) reduced NO production, iNOS mRNA,
and iNOS protein levels in a dose-dependent manner, without inhibition
of iNOS enzymatic activity. It reduced the binding of the NF-κB
p50 subunit to the biotinylated-consensus sequence and decreased nuclear
p65 translocation. Gallic acid as a subunit of the macrocyclic ellagitannin <b>1</b> showed a far lower inhibitory activity. Nitric oxide production
was reduced by <b>1</b> after stimulation using TLR2 (Pam2CSK4)
and TLR4 (Kdo2) agonists, but this compound did not inhibit inducible
nitric oxide synthesis after stimulation using interferon-gamma. IL-1beta,
IL-6, and TNF-alpha mRNA synthesis was clearly reduced by the addition
of <b>1</b>. Oenothein B (<b>1</b>) inhibits iNOS after
stimulation with LPS, TLR2, and TLR4 agonists via inhibition of TLR/NF-κB-dependent
inducible nitric oxide and cytokine synthesis independent from IFN-gamma/JAK/STAT
pathways. The full molecular structure of this macrocyclic ellagitannin
seems to be required for its immunomodulatory actions