title: Mitraphylline inhibits lipopolysaccharide-mediated activation of primary human neutrophils.
abstract: BACKGROUND
  Mitraphylline (MTP) is the major pentacyclic oxindolic alkaloid presented in Uncaria tomentosa. It has traditionally been used to treat disorders including arthritis, heart disease, cancer, and other inflammatory diseases. However, the specific role of MTP is still not clear, with more comprehensivestudies, our understanding of this ancient herbal medicine will continue growing.
  
  
  OBJECTIVE
  Some studies provided its ability to inhibit proinflamatory cytokines, such as TNF-α, through NF-κB-dependent mechanism. TNF-α primes neutrophils and modulates phagocytic and oxidative burst activities in inflammatory processes. Since, neutrophils represent the most abundant pool of leukocytes in human blood and play a crucial role in inflammation, we aimed to determine the ability of MTP to modulate neutrophil activation and differentially regulate inflammatory-related cytokines.
  
  
  METHODS
  To determine the mechanism of action of MTP, we investigated the effects on LPS-activated human primary neutrophils responses including activation surface markers by FACS and the expression of inflammatory cytokines, measured by real time PCR and ELISA.
  
  
  RESULTS
  Treatment with MTP reduced the LPS-dependent activation effects. Activated neutrophils (CD16(+)CD62L(-)) diminished after MTP administration. Moreover, proinflamatory cytokines (TNF-α, IL-6 or IL-8) expression and secretion were concomitantly reduced, similar to basal control conditions.
  
  
  CONCLUSIONS
  Taken together, our results demonstrate that MTP is able to elicit an anti-inflammatory response that modulates neutrophil activation contributing to the attenuation of inflammatory episodes. Further studies are need to characterize the mechanism by which MTP can affect this pathway that could provide a means to develop MTP as new candidate for inflammatory disease therapies.
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Seville, 41012, Seville, Spain ; Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, CSIC, Seville, Spain.
authors.forename: Sergio
authors.initials: S
authors.lastname: Montserrat-de la Paz
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Seville, 41012, Seville, Spain.
authors.forename: Angeles
authors.initials: A
authors.lastname: Fernandez-Arche
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Seville, 41012, Seville, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: de la Puerta
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Seville, 41012, Seville, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Quilez
authors.affiliation: Laboratory of Cellular and Molecular Nutrition, Instituto de la Grasa, CSIC, Seville, Spain.
authors.forename: Francisco J G
authors.initials: FJ
authors.lastname: Muriana
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Seville, 41012, Seville, Spain.
authors.forename: Maria Dolores
authors.initials: MD
authors.lastname: Garcia-Gimenez
authors.affiliation: Department of Pharmacology, School of Pharmacy, University of Seville, 41012, Seville, Spain . Electronic address: bbermudez@us.es.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bermudez
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D020948:Cat's Claw / Q000737:chemistry; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D026121:Indole Alkaloids / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008070:Lipopolysaccharides; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects*; D000078183:Oxindoles; D024301:Plant Bark / Q000737:chemistry; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C508606:CXCL8 protein, human; D016207:Cytokines; C508600:IL6 protein, human; D026121:Indole Alkaloids; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000078183:Oxindoles; D014409:Tumor Necrosis Factor-alpha; C509328:mitraphylline
keywords: Alkaloids; Inflammation; Lipopolysaccharide; Mitraphylline; Neutrophils; Uncaria tomentosa