Inhibition of NF-kappaB activation and iNOS induction by ent-kaurane diterpenoids in LPS-stimulated RAW264.7 murine macrophages.
Xerophilusin A (1), xerophilusin B (2), longikaurin B (3), and xerophilusin F (4) from Isodon xerophylus inhibit LPS-induced NO production in RAW 264.7 macrophages, with IC(50) values of 0.60, 0.23, 0.44, and 0.67 muM, respectively, and they all inhibited mRNA production in these same cells. They decreased the luciferase activity in RAW 264.7 cells transiently transfected with the NF-kappaB-dependent luciferase reporter, with IC(50) values of 1.8, 0.7, 1.2, and 1.6 muM, respectively. Compounds 1-3 reduced NF-kappaB activation, with compound 4 showing no effect, but p65 translocation from the cytoplasm to the nucleus and the LPS-induced degradation of IkappaB were inhibited by all four test compounds. These findings indicate that ent-kauranes are potential anti-inflammatory agents, with a specific mechanism in which both the inhibition of NF-kappaB translocation and the consequent decrease of pro-inflammatory mediators are implicated.
Aquila
Silvia
S
Departament de Farmacologia, Universitat de Valencia, Avenida Vicent Andres Estelles s/n, 46100 Burjassot, Valencia, Spain.
Weng
Zhi-Ying
ZY
Zeng
Yue-Qin
YQ
Sun
Han-Dong
HD
Ríos
José Luis
JL
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D045786:Diterpenes, Kaurane / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D037602:Isodon / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008156:Luciferases / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects*; D010946:Plants, Medicinal / Q000737:chemistry*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D045786:Diterpenes, Kaurane; D008070:Lipopolysaccharides; D016328:NF-kappa B; C410910:xerophilusin A; C410911:xerophilusin B; D009569:Nitric Oxide; D008156:Luciferases; D052247:Nitric Oxide Synthase Type II