title: Anti-inflammatory and antitumoural effects of Uncaria guianensis bark.
abstract: BACKGROUND
  Uncaria guianensis (Aublet) Gmell (Rubiaceae) is a medicinal plant from the jungles of South and Central America, used to treat cancer, arthritis, diabetes, and inflammation. Evaluate the anti-inflammatory and anti-tumor effects of Uncaria guianensis preparations.
  
  
  METHODS
  Bio-guided fractionation of a hydroethanolic extract of Uncaria guianensis was performed, evaluating the fractions and subfractions for their effect on inflammatory mediators, tumour necrosis factor alpha (TNF-α), interleukin 6 (IL-6) and prostaglandin E2 (PGE2) by ELISA and nitric oxide (NO) by the Griess reaction in cultured supernatant from RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). The expression of cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS) and inhibitor of κB (IκB) were investigated in RAW 264.7 macrophages by flow cytometry. The activity of NF-κB in HeLa cells transfected with a luciferase reporter system was determined. The effect of Uncaria guianensis on the inflammatory response in vivo was assessed in BALB/c mice stimulated with LPS, on rat paw oedema induced by carrageenan, and on tumour growth and lung metastasis in BALB/c mice inoculated with 4T1 mammary tumour cells. Immune cell infiltrates and inflammatory mediators were evaluated in the tumour by immunohistochemistry.
  
  
  RESULTS
  Sub-fraction Ug AIV inhibited, to varying degrees, NO, TNF-α, IL-6 and PGE2 production by macrophages in vitro (30 μg/ml) and in the serum of LPS-challenged mice (5 mg/kg). Macrophage expression of Cox-2 was inhibited (35%), IκB degradation was completely inhibited and NF-κB activation was inhibited (70%) by Ug AIV at 30 μg/ml. Ug AIV decreased paw oedema by 86% (5 mg/kg) and serum NO and TNF-α by 45% and 65% respectively. Ug AIV reduced 4T1 mammary tumour growth by 91% on day 33 post-inoculation as well as the levels of serum NO, IL-6 and TNF-α in the same animals. Ug AIV decreased the number of tumour-infiltrating T lymphocytes, macrophages and neutrophils as well as the number of cells positive for COX-2, iNOS, IL-6, TNF-α and p65.
  
  
  CONCLUSIONS
  As Ug AIV was not cytotoxic for tumour cells or macrophages, its anti-tumour effect may be due to a reduction in pro-tumoural inflammatory processes in the tumour microenvironment, possibly mediated through NF-κB.
authors.affiliation: Laboratorio de Patología Celular y Molecular, Centro de Medicina Experimental, Instituto Venezolano de Investigaciones Científicas, Apartado 20632, Caracas 1020-A, Venezuela.
authors.forename: I
authors.initials: I
authors.lastname: Urdanibia
authors.forename: F
authors.initials: F
authors.lastname: Michelangeli
authors.forename: M-C
authors.initials: MC
authors.lastname: Ruiz
authors.forename: B
authors.initials: B
authors.lastname: Milano
authors.forename: P
authors.initials: P
authors.lastname: Taylor
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002351:Carrageenan; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D008517:Phytotherapy; D024301:Plant Bark; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D032070:Uncaria
chemical_list: D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D020672:I-kappa B Proteins; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606205:Nfkbia protein, mouse; C000606206:Nfkbia protein, rat; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D002351:Carrageenan; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D015232:Dinoprostone
keywords: COX-2; IL; Il-6; IκB; LPS; NF-κB; NO; PGE(2); TNF-α; cyclooxygenase 2; iNOS; inducible nitric oxide synthase; inhibitor of κB; interleukin; lipopolysaccharide; nitric oxide; prostaglandin E(2); tumour necrosis factor alpha