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

Pharm Biol. 2017 Dec;55(1):435-440. doi: 10.1080/13880209.2016.1246574.

Abstract

Context: 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).

Materials and 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 IC50 values 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 IC50 values of 8.74 ± 0.31 and 12.08 ± 0.24 μM, respectively.

Discussion and conclusion: 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.

Keywords: BMDCs; CpG-DNA; Pro-inflammatory cytokines; mitogen-activated protein kinase.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / isolation & purification
  • Anti-Inflammatory Agents / pharmacology*
  • CpG Islands
  • Cytokines / metabolism
  • Dendritic Cells / drug effects*
  • Dendritic Cells / enzymology
  • Dose-Response Relationship, Drug
  • Enzyme Activation
  • Female
  • Genes, Reporter
  • HEK293 Cells
  • Humans
  • Inflammation Mediators / metabolism
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism*
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Norisoprenoids / isolation & purification
  • Norisoprenoids / pharmacology*
  • Oligonucleotides / genetics
  • Oligonucleotides / metabolism
  • Phosphorylation
  • Phytotherapy
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology*
  • Plants, Medicinal
  • Signal Transduction / drug effects*
  • Time Factors
  • Toll-Like Receptor 9 / antagonists & inhibitors*
  • Toll-Like Receptor 9 / genetics
  • Toll-Like Receptor 9 / metabolism
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / metabolism
  • Transcription, Genetic / drug effects
  • Transfection
  • Ulva / chemistry*

Substances

  • 3-hydroxyl-4,7-megastigmadien-9-one
  • Anti-Inflammatory Agents
  • Cytokines
  • Inflammation Mediators
  • NF-kappa B
  • Norisoprenoids
  • Oligonucleotides
  • Plant Extracts
  • Tlr9 protein, mouse
  • Toll-Like Receptor 9
  • Transcription Factor AP-1
  • Mitogen-Activated Protein Kinases