Journal
JOURNAL OF PHARMACY AND PHARMACOLOGY
Volume 72, Issue 9, Pages 1245-1255Publisher
OXFORD UNIV PRESS
DOI: 10.1111/jphp.13291
Keywords
anti-inflammatory response; brassinin; monocyte-to-macrophage differentiation; nuclear factor erythroid-derived 2-like 2; nuclear factor kappa-light-chain-enhancer of activated B cells
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Objectives The effects and molecular mechanisms of brassinin (BR), an indole phytoalexin from cruciferous vegetables, on monocyte-to-macrophage differentiation and inflammatory responses were investigated in this study. Methods Inflammatory responses from RAW264.7 cells and THP-1 were stimulated by lipopolysaccharide (1 mu g/ml), and monocyte-to-macrophage differentiation of THP-1 was induced by phorbol myristate acetate (50 ng/ml). The production of inflammatory mediators was determined by ELISA, Western blot or real-time PCR. Reactive oxygen species were examined by DCFH-DA assay. Key findings Brassinin at 50 mu m suppressed lipopolysaccharide-induced production of nitric oxide synthase, cyclooxygenase-2, prostaglandin E2 and reactive oxygen species by 90%, 69%, 52% and 41%, respectively, in RAW264.7 cells. In THP-1 cells, BR inhibited phorbol myristate acetate-induced monocyte-to-macrophage differentiation by suppressing cluster of differentiation molecule beta and CD36. In addition, BR suppressed translocation of nuclear factor 'kappa-light-chain-enhancer' of activated B cells (NF-kappa B) into the nucleus. However, BR activated the nuclear factor erythroid-derived 2-like 2 (Nrf2) and its target molecules hemoxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1), with an increase in nuclear translocation of Nrf2. Conclusions Brassinin suppressed monocyte-to-macrophage differentiation and inflammatory responses by differentially regulating Nrf2 and NF-kappa B signallings.
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