Scope: In this study, we investigate the underlying molecular mechanism of the effect of tectochrysin on LPS-primed macrophages.
Methods and results: As measured by western blot, RT-PCR, and ELISA, tectochrysin inhibits extracellular signal-related kinase 1/2 (ERK1/2) phosphorylation and sequentially suppressed downstream inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), and IL-6 transcription as well as the NO, TNF-α, and IL-6 in supernatant, but it does not affect extracellular signal-regulated kinase (MEK) phosphorylation levels. An enzyme reaction study shows that tectochrysin exerted an inhibitory effect on ERK1/2 phosphorylation by inactivating phosphorylated MEK1/2. Moreover, tectochrysin decreases arginase II expression in LPS-primed RAW264.7 macrophages via reduction of NO production. Tectochrysin also suppresses inflammatory mediator release in peritoneal lavage fluid and in the serum of LPS-induced endotoxemia mice.
Conclusion: Our data indicate that by directly inactivating p-MEK1/2, tectochrysin decreases the phosphorylation level of ERK and subsequently suppresses activator protein-1 (AP-1) activation to reduce pro-inflammatory mediator production, suggesting that tectochrysin has great potential for use in a nutritional preventive strategy against inflammation-related diseases.
Keywords: ERK; MEK; anti-inflammatory; macrophages; tectochrysin.
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