Methanol Extracts of Stewartia koreana Inhibit Cyclooxygenase-2 (COX-2) and Inducible Nitric Oxide Synthase (iNOS) Gene Expression by Blocking NF-κB Transactivation in LPS-activated RAW 264.7 Cells

  • Lee, Tae Hoon (Graduate School of Biotechnology and Institute of Life Sciences and Resources, Kyung Hee University) ;
  • Kwak, Han Bok (Department of Cell and Developmental Biology, Seoul National University School of Dentistry) ;
  • Kim, Hong-Hee (Department of Cell and Developmental Biology, Seoul National University School of Dentistry) ;
  • Lee, Zang Hee (Department of Cell and Developmental Biology, Seoul National University School of Dentistry) ;
  • Chung, Dae Kyun (Graduate School of Biotechnology and Institute of Life Sciences and Resources, Kyung Hee University) ;
  • Baek, Nam-In (Graduate School of Biotechnology and Institute of Life Sciences and Resources, Kyung Hee University) ;
  • Kim, Jiyoung (Graduate School of Biotechnology and Institute of Life Sciences and Resources, Kyung Hee University)
  • Received : 2007.01.13
  • Accepted : 2007.04.03
  • Published : 2007.06.30

Abstract

Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) are involved in various pathophysiological processes such as inflammation and carcinogenesis. In a search for inhibitors of COX-2 and iNOS production we found that extracts of Stewartia koreana strongly inhibited NO and $PGE_2$ production in LPS-treated macrophage RAW 264.7 cells. We have now shown that the mRNA and protein levels of iNOS and COX-2 are reduced by the Stewartia koreana extract (SKE). SKE inhibited expression of an NF-${\kappa}B$ reporter gene in response to LPS, and gel mobility shift assays revealed that SKE reduced NF-${\kappa}B$ DNA-binding activity. The extract also inhibited LPS-induced phosphorylation of $I{\kappa}B-{\alpha}$ and nuclear translocation of p65. Administration of the extract reduced the symptoms of arthritis in a collagen-induced arthritic mouse model. These results indicate that Stewartia extracts contain potentially useful agents for preventing and treating inflammatory diseases.

Keywords

Cyclooxygenase-2;Inflammation;Nitric Oxide Synthase;Nuclear factor ${\kappa}B$;Stewartia koreana

Acknowledgement

Supported by : Rural Development Administration

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