title: Potent anti-inflammatory and antiproliferative effects of gambogic acid in a rat model of antigen-induced arthritis.
abstract: BACKGROUND
  We have previously reported a continuous activation of caspase-1 and increased interleukin (IL)-1β levels in early rheumatoid arthritis (RA). These observations raised the hypothesis that drugs targeting the IL-1β pathway, in addition to tumour necrosis factor (TNF), may be particularly effective for early RA treatment. We have recently identified gambogic acid as a promising therapeutic candidate to simultaneously block IL-1β and TNF secretion. Our main goal here was to investigate whether gambogic acid administration was able to attenuate inflammation in antigen-induced arthritis (AIA) rats.
  
  
  METHODS
  Gambogic acid was administered to AIA rats in the early and late phases of arthritis. The inflammatory score, ankle perimeter, and body weight were evaluated during the period of treatment. Rats were sacrificed after 19 days of disease progression and paw samples were collected for histological and immunohistochemical evaluation.
  
  
  RESULTS
  We found that inflammation in joints was significantly suppressed following gambogic acid administration. Histological and immunohistochemical evaluation of treated rats revealed normal joint structures with complete abrogation of the inflammatory infiltrate and cellular proliferation.
  
  
  CONCLUSIONS
  Our results suggest that gambogic acid has significant anti-inflammatory properties and can possibly constitute a prototype anti-inflammatory drug with therapeutic efficacy in the treatment of inflammatory diseases such as RA.
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Cascão
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vidal
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Helena
authors.initials: H
authors.lastname: Raquel
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Neves-Costa
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal ; Gulbenkian Programme for Advanced Medical Education, Lisbon, Portugal.
authors.forename: Nuno
authors.identifier: 0000-0002-5582-0933
authors.initials: N
authors.lastname: Figueiredo
authors.affiliation: Department of Internal Medicine, Rush University Medical Center, Chicago, IL 60612, USA.
authors.forename: Vineet
authors.identifier: 0000-0001-6987-2550
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal ; Rheumatology Department, Centro Hospitalar de Lisboa Norte, EPE, Hospital de Santa Maria, Lisbon, Portugal.
authors.forename: João Eurico
authors.initials: JE
authors.lastname: Fonseca
authors.affiliation: Instituto de Medicina Molecular, Faculdade de Medicina da Universidade de Lisboa, Lisbon, Portugal.
authors.forename: Luis Ferreira
authors.identifier: 0000-0003-0707-315X
authors.initials: LF
authors.lastname: Moita
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000627:therapeutic use*; D000941:Antigens / Q000737:chemistry; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D020170:Caspase 1 / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D044004:Xanthones / Q000627:therapeutic use*
chemical_list: D000893:Anti-Inflammatory Agents; D000941:Antigens; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D044004:Xanthones; C052659:gambogic acid; D020170:Caspase 1