tectochrysin and Endotoxemia

In this study, we investigate the underlying molecular mechanism of the effect of tectochrysin on LPS-primed macrophages.. 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.. 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.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arginase; Endotoxemia; Flavonoids; Interleukin-6; Lipopolysaccharides; Male; MAP Kinase Kinase 1; MAP Kinase Kinase 2; Mice; Mice, Inbred BALB C; Nitric Oxide; Nitric Oxide Synthase Type II; Protein Kinase Inhibitors; RAW 264.7 Cells; Tumor Necrosis Factor-alpha