394회 Discovery and Mode of Action of NF-κB inhibitors from Natural Pro…

394회  

일시: 2006. 09. 07

연사: 이정형, 자연과학대학 생명과학부 생화학과

제목: Discovery and Mode of Action of NF-κB inhibitors from Natural Products.

Abstract

NF-κB regulates the transcription of a large number of genes, particularly those involved in immune, inflammatory, and antiapoptotic responses. Inappropriate regulation of NF-κB is directly involved in a wide range of human disorders, including a variety of cancers, neurodegenerative diseases, ataxiatelangiectasia, arthritis, asthma, inflammatory bowel disease, and numerous other inflammatory conditions. Recently, NF-κB and the signaling pathways that regulate its activity have become a focal point for intense drug discovery and development efforts. Well-known antiinflammatory substances such as glucocorticoids or aspirin and salicylate exert, at least a part of their effects, by inhibiting NF-κB activity. Several antiinflammatory medicinal plants also contain structurally diverse compounds that inhibit NF-κB activation. In our search for inhibitors of NF-κB activation from natural products, we identified dozens of compounds from several medicinal plants such as Celastrus orbiculatus. Isodon japonicus, Alpina cochingera, Artemisia sylvatica, and Inula britanica. These inhibitors were categorized into three groups based on the mode of action. One group of inhibitors interferes with the induced degradation of IκB family members by inhibiting IκB kinase. Another group of inhibitors exerts their effects only in the cell nucleus by impairing the transcriptional activity of RelA subunit of NF-κB. Further group of inhibitors interferes with DNA-binding activity of NF-κB by directly targeting p50 subunit. In this seminar, it will be present and discussed an IκB kinase inhibitor and a transcriptional activity inhibitor of RelA(p65).