Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Quercetin Derivatives from Siegesbeckia glabrescens Inhibit the Expression of COX-2 Through the Suppression of NF-κB Activation in Microglia

  • Lim, Hyo-Jin (College of Pharmacy, Sookmyung Women's University) ;
  • Li, Hua (College of Pharmacy, Sookmyung Women's University) ;
  • Kim, Jae-Yeon (College of Pharmacy, Sookmyung Women's University) ;
  • Ryu, Jae-Ha (College of Pharmacy, Sookmyung Women's University)
  • Received : 2010.10.11
  • Accepted : 2010.11.09
  • Published : 2011.01.31
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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 $E_2$ ($PGE_2$) 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 $IC_{50}$ 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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References

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