Inhibition of nuclear factor-kappaB activation by 2',8''-biapigenin.
Inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) play a key role in the inflammatory processes. Improper overproduction of NO and prostaglandins by both enzymes are also believed to be involved in the pathogenesis of certain human cancers. Crude extracts of Selaginella tamariscina are used as an oriental medicine, which has been reported to inhibit the production of proinflammatory cytokines and cause cell cycle arrest. We isolated 2',8''-biapigenin from S. tamariscina and investigated whether it modulates iNOS and COX-2 expressions in Raw264.7 macrophages stimulated with lipopolysaccharide (LPS). We found that 2',8''-biapigenin blocked the transactivations of iNOS and COX-2 genes via the inactivation of nuclear factor-kappaB by preventing the nuclear translocation of p65. Hence, it may be possible to develop S. tamariscina extracts or 2',8''-biapigenin as a useful agent for cancer chemoprevention or for the treatment of inflammatory diseases.
Woo
Eun-Rhan
ER
College of Pharmacy, Chosun University, Gwangju, South Korea.
Pokharel
Yuba Raj
YR
Yang
Jin Won
JW
Lee
Song Yi
SY
Kang
Keon Wook
KW
D047310:Apigenin / Q000494:pharmacology*; D044946:Biflavonoids / Q000494:pharmacology*; D015153:Blotting, Western; D002467:Cell Nucleus / Q000737:chemistry / Q000187:drug effects; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000096:biosynthesis; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017930:Genes, Reporter / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D008156:Luciferases / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects / Q000201:enzymology; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D032503:Selaginellaceae / Q000737:chemistry
D044946:Biflavonoids; D052246:Cyclooxygenase 2 Inhibitors; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D016328:NF-kappa B; C446502:biapigenin; D047310:Apigenin; D008156:Luciferases; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone