New sesquiterpene dimers from Inula britannica inhibit NF-kappaB activation and NO and TNF-alpha production in LPS-stimulated RAW264.7 cells.
A bioassay-guided isolation of an ethyl acetate-soluble extract of the aerial parts of Inula britannica var. chinensis (Rupr.) Regel, using an in vitro NF-kappaB reporter gene assay, led to the isolation of four new sesquiterpene dimers bearing a norbornene moiety, inulanolides A-D, and three known sesquiterpenes, 1,6alpha-dihydroxyeriolanolide, 1-acetoxy-6alpha-hydroxyeriolanolide, and eupatolide. The structures of the new compounds were elucidated by spectroscopic methods. Among these compounds, inulanolides B and D and eupatolide, exhibited potent inhibitory activity on the LPS-induced NF-kappaB activation with IC50 values of 0.49 microM, 0.48 microM, and 1.54 microM, respectively. Consistent with their inhibitory effect on NF-kappaB activation, compounds and also strongly inhibited the production of NO and TNF-alpha in the LPS-stimulated RAW264.7 cells with IC50 values in the range of 2 microM.
Jin
Hui Zi
HZ
Anticancer Research Laboratory, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
Lee
Dongho
D
Lee
Jeong Hyung
JH
Lee
Kyeong
K
Hong
Young-Soo
YS
Choung
Dong-Ho
DH
Kim
Young Ho
YH
Lee
Jung Joon
JJ
D000818:Animals; D002460:Cell Line; D020128:Inhibitory Concentration 50; D038143:Inula / Q000737:chemistry*; D008070:Lipopolysaccharides; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000187:drug effects*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D012717:Sesquiterpenes; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase