Furanodien-6-one from Commiphora erythraea inhibits the NF-κB signalling and attenuates LPS-induced neuroinflammation.
We investigated the in vitro anti-inflammatory activity of 1(10),4-furanodien-6-one, one the most active compounds of the hexane extract of Commiphora erythraea (Ehrenb.) Engl., by exposing microglial BV-2 cells to lipopolysaccharide. We showed that furanodien-6-one pre-treatment restored cell viability and ROS to control levels while halving NO generation. Production of pro-inflammatory IL-6, IL-23, IL-17, TGF-β, and INF-γ, significantly induced by LPS, was also markedly reduced by furanodien-6-one treatment. We further showed that furanodien-6-one protects primary neuronal cultures against the inflammatory/toxic insults of LPS-treated BV-2 conditioned media, indicating that furanodien-6-one exerts anti-inflammatory/cytoprotective effects in neuronal cells. We then investigated whether furanodien-6-one exerts anti-inflammatory properties in an in vivo model of microglial activation. In adult mice ip-injected with LPS we found that furanodien-6-one had strong cerebral anti-inflammatory properties by inhibiting liver and brain TNFα as well as IL-1β expression. Results were not unexpected since FTIR-metabolomic analyses showed that furanodien-6-one-treated mice had a reduced dissimilarity to control animals and that the response to LPS treatment was markedly modified by furanodien-6-one. In conclusion our data provide strong evidence of the anti-inflammatory properties of furanodien-6-one that could be exploited to counteract degenerative pathologies based on neuroinflammation.
Dipartimento di Medicina Sperimentale Scienze Biochimiche, Università di Perugia, 06123 Perugia, Italy. ilaria.bellezza@unipg.it
Ilaria
I
Bellezza
Annalisa
A
Mierla
Silvia
S
Grottelli
Maria Carla
MC
Marcotullio
Federica
F
Messina
Luca
L
Roscini
Gianluigi
G
Cardinali
Massimo
M
Curini
Alba
A
Minelli
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D054022:Cerebrum / Q000187:drug effects / Q000378:metabolism; D029744:Commiphora / Q000737:chemistry*; D005663:Furans / Q000302:isolation & purification / Q000494:pharmacology*; D006574:Heterocyclic Compounds, 2-Ring / Q000302:isolation & purification / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009443:Neuritis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D005663:Furans; D006574:Heterocyclic Compounds, 2-Ring; D053583:Interleukin-1beta; D007378:Interleukins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; C442489:furanodiene; D009569:Nitric Oxide; D007371:Interferon-gamma