title: Anti-inflammatory activity of new compounds from Andrographis paniculata by NF-kappaB transactivation inhibition.
abstract: Previous studies showed that the ethyl acetate (EtOAc) fraction of Andrographis paniculata (AP) possessed anti-inflammatory activity. This study further isolated these active compounds from bioactivity-guided chromatographic fractionation and identified eight pure compounds. Reporter gene assay indicated that 5-hydroxy-7,8-dimethoxyflavone (1), 5-hydroxy-7,8-dimethoxyflavanone (2), a mix of beta-sitosterol (3a) and stigmasterol (3b), ergosterol peroxide (4), 14-deoxy-14,15-dehydroandrographolide (5), and a new compound, 19-O-acetyl-14-deoxy-11,12-didehydroandrographolide (6a), significantly inhibited the transcriptional activity of NF-kappaB in LPS/IFN-gamma stimulated RAW 264.7 macrophages (P < 0.05). The two most abundant compounds, 14-deoxy-11,12-didehydroandrographolide (7) and andrographolide (8), had less inhibitory activity but exerted greater inhibitory activity by hydrogenation, oxidation, or acetylation to become four derived compounds, 9, 10, 11, and 12. All of the compounds significantly decreased TNF-alpha, IL-6, macrophage inflammatory protein-2 (MIP-2), and nitric oxide (NO) secretions from LPS/IFN-gamma stimulated RAW 264.7 cells. Compounds 5, 11, and 12 exerted the strongest inhibitory effect on NF-kappaB-dependent transactivation in the RAW 264.7 cell, with IC(50) values of 2, 2.2, and 2.4 microg/mL, respectively, providing encouraging results for bioactive compound development.
authors.affiliation: Department of Biochemical Science and Technology, National Taiwan University, Taipei 10617, Taiwan.
authors.forename: Wen-Wan
authors.initials: WW
authors.lastname: Chao
authors.forename: Yueh-Hsiung
authors.initials: YH
authors.lastname: Kuo
authors.forename: Bi-Fong
authors.initials: BF
authors.lastname: Lin
mesh_terms: D035685:Andrographis / Q000235:genetics*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D004224:Diterpenes / Q000032:analysis / Q000378:metabolism; D017930:Genes, Reporter; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D010936:Plant Extracts / Q000032:analysis / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation / Q000235:genetics*
chemical_list: D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; C030419:andrographolide; D007371:Interferon-gamma