Dimethyl cardamonin inhibits lipopolysaccharide-induced inflammatory factors through blocking NF-kappaB p65 activation.

This study has found that dimethyl cardamonin (2',4'-dihydroxy-6'-methoxy-3',5'-dimethylchalcone; DMC), a naturally occurring chalcone, showed potent anti-inflammatory effects in vitro and in vivo. In a cellular model of inflammation, DMC inhibited production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) and attenuated expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-1 beta, inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2). DMC prevented nuclear translocation of the nuclear factor-kappaB (NF-kappaB) p65 subunit by reducing inhibitor of kappaB alpha (I-kappaB alpha) phosphorylation and degradation, which resulted in a suppression of NF-kappaB activities for its target genes. In a mouse model of endotoxin shock, the intraperitoneal injection (i.p.) of DMC (1-50mg/kg) suppressed TNF-alpha, IL-6 and IL-1 beta secretion in LPS-induced mouse blood serum. These results suggest that DMC exerts anti-inflammatory effects through blocking NF-kappaB activation, therefore, DMC may act as an effective therapeutic strategy against a variety of inflammatory diseases. (c) 2010 Elsevier B.V. All rights reserved.