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Title

Friedelane-type triterpenoids as selective anti-inflammatory agents by regulation of differential signaling pathways in LPS-stimulated macrophages

AuthorsVillar-Lorenzo, Andrea; Ardiles, Alejandro E.; Arroba, Ana I. ; Pardo, Virginia; López-Collazo, Eduardo; Bazzocchi, Isabel L.; González-Rodríguez, Águeda; Valverde, Ángela M.
KeywordsLipopolysaccharide
Inflammation
Antioxidant enzymes
Nitric oxide synthase
Triterpenoids
Macrophages
Issue Date2016
PublisherElsevier
CitationToxicology and Applied Pharmacology 313: 57-67 (2016)
AbstractA series of 31 pentacyclic triterpenoids isolated from the root barks of Celastrus vulcanicola and Maytenus jelskii were tested for cytotoxicity and inhibitory activity against lipopolysaccharide (LPS)-induced nitric oxide (NO) production in RAW 264.7 macrophages. Compounds 18 (C18) and 25 (C25) exhibited significant inhibition of LPS-induced NO release at 50 and 25 μM concentrations, respectively, and decreased mRNAs of pro-inflammatory cytokines. At the molecular level, C18 neither inhibited LPS-mediated phosphorylation of mitogen activated protein kinases (MAPKs) nor nuclear translocation of nuclear factor kappa beta (NFκB). Instead, C18 enhanced and prolonged nuclear translocation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and increased the expression of its target genes including hemeoxigenase 1 (HO1). C25 efficiently inhibited LPS-mediated phosphorylation of JNK, p38 and ERK, without affecting NFκB or Nrf2 signaling pathways. Both compounds reduced LPS-mediated processing of caspase-1 and the cleavage of interleukin 1β (IL1β) proform, reflecting their ability to target the inflammasome. C25 also counteracted LPS effects on iNOS expression and pro-inflammatory cytokines mRNA levels in Bv-2 microglial cells. The anti-inflammatory effect of both compounds was also assessed in human macrophages. Our results suggest that triterpenoids C18 and C25 possess anti-inflammatory effects, which may be therapeutically relevant for diseases linked to inflammation.
URIhttp://hdl.handle.net/10261/151059
DOI10.1016/j.taap.2016.10.004
Identifiersdoi: 10.1016/j.taap.2016.10.004
e-issn: 1096-0333
issn: 0041-008X
Appears in Collections:(IIBM) Artículos
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