title: Suppression of lipopolysaccharide-induced nuclear factor-kappaB activity by theaflavin-3,3'-digallate from black tea and other polyphenols through down-regulation of IkappaB kinase activity in macrophages.
abstract: We investigated the inhibition of IkappaB kinase (IKK) activity in lipopolysaccharide (LPS)-activated murine macrophages (RAW 264.7 cell line) by various polyphenols including (-)-epigallocatechin-3-gallate, theaflavin, a mixture of theaflavin-3 gallate and theaflavin-3'-gallate, theaflavin-3,3'-digallate (TF-3), pyrocyanidin B-3, casuarinin, geraniin, and penta-O-galloyl-beta-D-glucose (5GG). TF-3 inhibited IKK activity in activated macrophages more strongly than did the other polyphenols. TF-3 strongly inhibited both IKK1 and IKK2 activity and prevented the degradation of IkappaBalpha and IkappaBbeta in activated macrophage cells. The results suggested that the inhibition of IKK activity by TF-3 could occur by a direct effect on IKKs or on upstream events in the signal transduction pathway. Furthermore, geraniin, 5GG, and TF-3 all blocked phosphorylation of IKB from the cytosolic fraction, inhibited nuclear factor-kappaB (NFkappaB) activity, and inhibited increases in inducible nitric oxide synthase levels in activated macrophages. These results suggest that TF-3 may exert its anti-inflammatory and cancer chemopreventive actions by suppressing the activation of NFkappaB through inhibition of IKK activity.
authors.affiliation: Institute of Biochemistry, College of Medicine, National Taiwan University, Taipei.
authors.forename: M H
authors.initials: MH
authors.lastname: Pan
authors.forename: S Y
authors.initials: SY
authors.lastname: Lin-Shiau
authors.forename: C T
authors.initials: CT
authors.lastname: Ho
authors.forename: J H
authors.initials: JH
authors.lastname: Lin
authors.forename: J K
authors.initials: JK
authors.lastname: Lin
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D044946:Biflavonoids; D002392:Catechin; D002478:Cells, Cultured; D015536:Down-Regulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005960:Glucosides / Q000494:pharmacology; D047348:Hydrolyzable Tannins; D051550:I-kappa B Kinase; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010636:Phenols / Q000494:pharmacology*; D010766:Phosphorylation; D011108:Polymers / Q000494:pharmacology*; D059808:Polyphenols; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013634:Tannins / Q000494:pharmacology; D013662:Tea / Q000737:chemistry
chemical_list: D000975:Antioxidants; D044946:Biflavonoids; D004791:Enzyme Inhibitors; D005419:Flavonoids; D005960:Glucosides; D047348:Hydrolyzable Tannins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010636:Phenols; D011108:Polymers; D059808:Polyphenols; D013634:Tannins; D013662:Tea; D009569:Nitric Oxide; C077197:theaflavin digallate; C435084:pentagalloylglucose; C024603:Geraniin; D005707:Gallic Acid; D002392:Catechin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D017346:Protein Serine-Threonine Kinases; C496564:Chuk protein, mouse; D051550:I-kappa B Kinase; C496562:Ikbkb protein, mouse; C496566:Ikbke protein, mouse