title: Pharmacological effects of mitraphylline from Uncaria tomentosa in primary human monocytes: Skew toward M2 macrophages.
abstract: BACKGROUND
  Uncaria tomentosa (Willdenow ex Roemer & Schultes) DC. (Rubiaceae) is a Peruvian thorny liana, commonly known as "cat׳s claw", and traditionally used in folk medicine to deal with several inflammatory diseases. Mitraphylline (MTP) is the most abundant pentacyclic oxindolic alkaloid (POA) from U. Tomentosa and has been reported to modify the inflammatory response. Herein, we have sought to identify the mechanisms underlying this modulatory effect of MTP on primary human monocytes and its ability to regulate differentiation processes on human primary monocyte and monocyte-derived macrophages.
  
  
  METHODS
  In vitro studies with human primary monocytes and monocyte-derived macrophages were performed. Monocytes and M0 macrophages were exposed to MTP (25μM) and LPS (100ng/mL). M0 macrophages were polarized to M1 and M2 phenotypes in the absence or presence of MTP. The activation state of monocytes/macrophages was assessed by flow cytometry, gene expression and protein analysis of different specific markers.
  
  
  RESULTS
  In human primary monocytes, the incubation of MTP for 24h reduced the number of classical (CD14(++)CD16(-)) and intermediate (CD14(++)CD16(+)) subsets when compared to untreated or LPS-treated cells. MTP also reduced the chemotactic capacity of human primary monocytes. In addition, MTP promoted the polarization of M0 macrophages toward an anti-inflammatory M2 phenotype, the abrogation of the release of pro-inflammatory cytokines such as TNFα, IL-6 or IL-1β, as well as the restoration of markers for M2 macrophages in LPS-treated M1 macrophages.
  
  
  CONCLUSIONS
  Our results suggest that MTP may be a key modulator for regulating the plasticity of monocytes/macrophages and the attenuation of the inflammatory response.
authors.affiliation: Department of Pharmacology. School of Pharmacy. University of Seville, Spain; Laboratory of Cellular and Molecular Nutrition. Instituto de la Grasa, CSIC, Seville, Spain.
authors.forename: S
authors.initials: S
authors.lastname: Montserrat-de la Paz
authors.affiliation: Department of Pharmacology. School of Pharmacy. University of Seville, Spain.
authors.forename: R
authors.initials: R
authors.lastname: de la Puerta
authors.affiliation: Department of Pharmacology. School of Pharmacy. University of Seville, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Fernandez-Arche
authors.affiliation: Department of Pharmacology. School of Pharmacy. University of Seville, Spain.
authors.forename: A M
authors.initials: AM
authors.lastname: Quilez
authors.affiliation: Laboratory of Cellular and Molecular Nutrition. Instituto de la Grasa, CSIC, Seville, Spain.
authors.forename: F J G
authors.initials: FJ
authors.lastname: Muriana
authors.affiliation: Department of Pharmacology. School of Pharmacy. University of Seville, Spain.
authors.forename: M D
authors.initials: MD
authors.lastname: Garcia-Gimenez
authors.affiliation: Department of Pharmacology. School of Pharmacy. University of Seville, Spain. Electronic address: bbermudez@us.es.
authors.forename: B
authors.initials: B
authors.lastname: Bermudez
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D020948:Cat's Claw / Q000737:chemistry*; D002454:Cell Differentiation / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D026121:Indole Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity; D008264:Macrophages / Q000166:cytology / Q000187:drug effects*; D009000:Monocytes / Q000166:cytology / Q000187:drug effects*; D000078183:Oxindoles
chemical_list: D015415:Biomarkers; D016207:Cytokines; D026121:Indole Alkaloids; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D000078183:Oxindoles; C509328:mitraphylline
keywords: Macrophages; Mitraphylline (Pubchem CID: 94160); Monocytes; Polarization and inflammatory diseases; Uncaria tomentosa; mitraphylline