Inhibition of NF-κB-dependent cytokine and inducible nitric oxide synthesis by the macrocyclic ellagitannin oenothein B in TLR-stimulated RAW 264.7 macrophages

Journal of Natural Products
Diethart SchmidThomas Moeslinger

Abstract

Immunomodulatory effects of oenothein B (1), a macrocyclic ellagitannin from various Onagraceae species, have been described previously. However, the mechanisms underlying the anti-inflammatory activity of 1 have not been fully clarified. The effects of 1 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 1 (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 1 showed a far lower inhibitory activity. Nitric oxide production was reduced by 1 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 1. Oenothein B (1) inhibits iNOS after stimulation with LPS, TLR2, and TLR4 agonists via inhibition of TLR/NF-κB-dependent ind...Continue Reading

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Citations

Aug 2, 2013·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Hong-Wu WangQin Ning
Jun 2, 2012·Gastroenterology Research and Practice·Siriboon AttasaranyaBancha Ovartlarnporn
Jan 25, 2013·International Journal of Molecular Sciences·Morio YoshimuraTakashi Yoshida
Sep 10, 2014·Journal of Ethnopharmacology·Sebastian GranicaAnna K Kiss
Feb 9, 2016·Journal of Agricultural and Food Chemistry·Ching-Peng ChiuYang-Chang Wu
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Oct 19, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shaoxia YeZhimin Zhao
May 25, 2016·Phytotherapy Research : PTR·Igor A SchepetkinMark T Quinn

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