title: 3-Hydroxy-4,7-megastigmadien-9-one, isolated from Ulva pertusa, attenuates TLR9-mediated inflammatory response by down-regulating mitogen-activated protein kinase and NF-κB pathways.
abstract: BACKGROUND
  Seaweeds are rich in bioactive compounds in the form of vitamins, phycobilins, polyphenols, carotenoids, phycocyanins and polysaccharides; many of these are known to have advantageous applications in human health. 3-Hydroxy-4,7-megastigmadien-9-one (comp) was isolated from Ulva pertusa (U. pertusa) Kjellman (Ulvaceae), which is a familiar edible green seaweed.
  
  
  OBJECTIVE
  This study evaluates the anti-inflammatory activity of comp in CpG DNA-stimulated bone marrow-derived dendritic cells (BMDCs).
  
  
  METHODS
  For evaluating the effect of comp on cytokines production, BMDCs were treated with doses of comp (0, 0.5, 1, 2, 5, 10, 25 and 50 μM) for 1 h before stimulation with CpG DNA (1 μM). Cytokine production was measured by ELISA. Western blotting was conducted for evaluating effect of comp (50 μM) on MAPKs and NF-κB pathways. Luciferase reporter gene assay was conducted for effect of comp (0, 5, 10 and 25 μM) on transcriptional activity of AP-1 and NF-κB.
  
  
  RESULTS
  Comp exhibited strong inhibition of interleukin (IL)-12 p40, IL-6 and TNF-α cytokine production with IC50values of 6.02 ± 0.35, 27.14 ± 0.73, and 7.56 ± 0.21 μM, respectively. It blocked MAPKs and NF-κB pathways by inhibiting the phosphorylation of ERK1/2, JNK1/2, p38 and IκBα. In addition, it strongly inhibited the transcriptional activity of AP-1 and NF-κB with IC50values of 8.74 ± 0.31 and 12.08 ± 0.24 μM, respectively.
  
  
  CONCLUSIONS
  Taken together, these data suggest that comp has a significant anti-inflammatory property and warrants further studies concerning the potential of comp for medicinal use.
authors.affiliation: a School of Medicine and Brain Korea 21 PLUS Program , Jeju National University , Jeju , South Korea.|b Institute of Medical Science, Jeju National University , Jeju , South Korea.
authors.forename: Irshad
authors.initials: I
authors.lastname: Ali
authors.affiliation: a School of Medicine and Brain Korea 21 PLUS Program , Jeju National University , Jeju , South Korea.|b Institute of Medical Science, Jeju National University , Jeju , South Korea.
authors.forename: Zahid
authors.initials: Z
authors.lastname: Manzoor
authors.affiliation: a School of Medicine and Brain Korea 21 PLUS Program , Jeju National University , Jeju , South Korea.|b Institute of Medical Science, Jeju National University , Jeju , South Korea.
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Koo
authors.affiliation: c Department of Chemistry and Cosmetics, College of Natural Sciences , Jeju National University , Jeju , South Korea.
authors.forename: Jung-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: c Department of Chemistry and Cosmetics, College of Natural Sciences , Jeju National University , Jeju , South Korea.
authors.forename: Sang-Hee
authors.initials: SH
authors.lastname: Byeon
authors.affiliation: a School of Medicine and Brain Korea 21 PLUS Program , Jeju National University , Jeju , South Korea.|b Institute of Medical Science, Jeju National University , Jeju , South Korea.
authors.forename: Eun-Sook
authors.initials: ES
authors.lastname: Yoo
authors.affiliation: a School of Medicine and Brain Korea 21 PLUS Program , Jeju National University , Jeju , South Korea.|b Institute of Medical Science, Jeju National University , Jeju , South Korea.
authors.forename: Hee-Kyoung
authors.initials: HK
authors.lastname: Kang
authors.affiliation: a School of Medicine and Brain Korea 21 PLUS Program , Jeju National University , Jeju , South Korea.|b Institute of Medical Science, Jeju National University , Jeju , South Korea.
authors.forename: Jin-Won
authors.initials: JW
authors.lastname: Hyun
authors.affiliation: c Department of Chemistry and Cosmetics, College of Natural Sciences , Jeju National University , Jeju , South Korea.
authors.forename: Nam-Ho
authors.initials: NH
authors.lastname: Lee
authors.affiliation: a School of Medicine and Brain Korea 21 PLUS Program , Jeju National University , Jeju , South Korea.|b Institute of Medical Science, Jeju National University , Jeju , South Korea.
authors.forename: Young-Sang
authors.initials: YS
authors.lastname: Koh
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D018899:CpG Islands; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005260:Female; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D045792:Norisoprenoids / Q000302:isolation & purification / Q000494:pharmacology*; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D051217:Toll-Like Receptor 9 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D044445:Ulva / Q000737:chemistry*
chemical_list: C528304:3-hydroxyl-4,7-megastigmadien-9-one; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D016328:NF-kappa B; D045792:Norisoprenoids; D009841:Oligonucleotides; D010936:Plant Extracts; C495370:Tlr9 protein, mouse; D051217:Toll-Like Receptor 9; D018808:Transcription Factor AP-1; D020928:Mitogen-Activated Protein Kinases
keywords: BMDCs; CpG-DNA; Pro-inflammatory cytokines; mitogen-activated protein kinase