ScholarWorks@숙명여자대학교

초록

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 E-2 (PGE(2)) 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 PGE(2) 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 PGE(2) production in LPS-activated microglia with their IC50 values of 7.1, 4.9, 4.4, 12.4 mu M respectively. They reduced the expression of protein and mRNA of COX-2 through the inhibition of I-kappa B alpha degradation and NF-kappa B 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 PGE(2) and suppression of COX-2 overexpression.

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