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

• Published in: International immunopharmacology Vol. 10; no. 9; pp. 1127 - 1134
• Main Authors: Kim, Young-Joo, Ko, Hyeonseok, Park, Jin-Soo, Han, Im-Ho, Amor, Evangeline C, Lee, Jong Wha, Yang, Hyun Ok
• Format: Journal Article
• Language: English
• Published: Netherlands 01.09.2010
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Chalcones - pharmacology; Cyclooxygenase 2 - analysis; Dinoprostone - analysis; Inflammation - drug therapy; Inflammation Mediators - antagonists & inhibitors; Interleukin-1beta - analysis; Interleukin-6 - analysis; Lipopolysaccharides - immunology; Macrophages - drug effects; Male; Mice; Mice, Inbred ICR; Nitric Oxide - analysis; Nitric Oxide Synthase Type II - analysis; Phosphorylation; Shock, Septic - chemically induced; Shock, Septic - drug therapy; Transcription Factor RelA - antagonists & inhibitors; Tumor Necrosis Factor-alpha - analysis
• ISSN: 1878-1705
• DOI: 10.1016/j.intimp.2010.06.017

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.