title: Zedoarondiol isolated from the rhizoma of Curcuma heyneana is involved in the inhibition of iNOS, COX-2 and pro-inflammatory cytokines via the downregulation of NF-kappaB pathway in LPS-stimulated murine macrophages.
abstract: Several sesquiterpene lactones that have been isolated from medicinal plants are known to have many pharmacological activities. In this study, we investigated the anti-inflammatory effects of zedoarondiol, a sesquiterpene lactone isolated from the rhizoma of Curcuma heyneana, in lipopolysaccharide (LPS)-stimulated macrophage cells. Zedoarondiol dose-dependently inhibited LPS-stimulated nitric oxide (NO), prostaglandin E(2) (PGE(2)), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), and interleukin-1beta (IL-1beta) productions in RAW 264.7 macrophage and in mouse peritoneal macrophage cells. Consistent with these findings, in RAW 264.7 cells, zedoarondiol suppressed the LPS-stimulated protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) and the mRNA expressions of iNOS, COX-2, TNF-alpha, IL-6, and IL-1beta in a concentration-dependent manner. Moreover, molecular data revealed that zedoarondiol inhibited LPS-stimulated DNA binding activity and the transcription activity of nuclear factor-kappa B (NF-kappaB), and this effect was accompanied by decreases in the degradation and phosphorylation of inhibitory kappaB (IkappaB)-alpha, and in the subsequent blocking of NF-kappaB translocations to the nucleus. Furthermore, zedoarondiol attenuated the phosphorylations of IkappaB kinase (IKK), extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38), and c-Jun N-terminal kinase (JNK) in LPS-stimulated RAW 264.7 cells. Taken together, the findings of the present study indicate that zedoarondiol inhibits iNOS, COX-2, and pro-inflammatory cytokine expressions by suppressing the phosphorylations of IKK and MAPKs, and by subsequently inactivating the NF-kappaB pathway. These relations reveal, in part, the mechanism underlying the anti-inflammatory properties of zedoarondiol.
authors.affiliation: Department of Pharmaceutical Biochemistry, Kyung-Hee University, Seoul, Republic of Korea.
authors.forename: Woong
authors.initials: W
authors.lastname: Cho
authors.forename: Joo-Won
authors.initials: JW
authors.lastname: Nam
authors.forename: Hyun-Jun
authors.initials: HJ
authors.lastname: Kang
authors.forename: Tri
authors.initials: T
authors.lastname: Windono
authors.forename: Eun-Kyoung
authors.initials: EK
authors.lastname: Seo
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D030024:Curcuma; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015536:Down-Regulation; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D007783:Lactones / Q000494:pharmacology* / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors*; D008517:Phytotherapy; D027343:Rhizome; D012717:Sesquiterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D007783:Lactones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D012717:Sesquiterpenes; C546347:zedoarondiol; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2