Abstract
The activation of microglia induces the overproduction of inflammatory mediators that are responsible for the neurodegenerative disorders including Alzheimer's disease and Parkinson's disease. The large amounts of prostaglandin <TEX>$E_2$</TEX> (<TEX>$PGE_2$</TEX>) produced by inducible cyclooxygenase (COX-2) is one of the main inflammatory mediators that can contribute to neurodegeneration. The inhibition of COX-2 thus may provide therapeutic strategy for the treatment of neurodegenerative diseases. From the activity-guided purification of EtOAc soluble fraction of Siegesbeckia glabrescens, four compounds were isolated as inhibitors of <TEX>$PGE_2$</TEX> production in LPS-activated microglia. Their structures were determined as 3, 4'-dimethylquercetin (1), 3, 7-dimethylquercetin (2), 3-methylquercetin (3) and 3, 7, 4'-trimethylquercetin (4) by the mass and NMR spectral data analysis. The compounds 1-4 showed dose-dependent inhibition of <TEX>$PGE_2$</TEX> production in LPS-activated microglia with their <TEX>$IC_{50}$</TEX> values of 7.1, 4.9, 4.4, <TEX>$12.4\;{\mu}M$</TEX> respectively. They reduced the expression of protein and mRNA of COX-2 through the inhibition of I-<TEX>${\kappa}B{\alpha}$</TEX> degradation and NF-<TEX>$\kappa}B$</TEX> activity that were correlated with the inactivation of p38 and ERK. Therefore the active compounds from Siegesbeckia glabrescens may have therapeutic effects on neuro-inflammatory diseases through the inhibition of overproduction of <TEX>$PGE_2$</TEX> and suppression of COX-2 overexpression.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have