title: Cymbopogon citratus as source of new and safe anti-inflammatory drugs: bio-guided assay using lipopolysaccharide-stimulated macrophages.
abstract: BACKGROUND
  Aqueous extracts of Cymbopogon citratus (Cy) leaves are used in traditional medicine for the treatment of inflammatory conditions, however, little is known about their mechanism of action.
  
  
  OBJECTIVE
  The aim of this study is to explore the anti-inflammatory properties of Cymbopogon citratus leaves and their polyphenol-rich fractions (PFs), as well its mechanism of action in murine macrophages.
  
  
  METHODS
  A lipid- and essential oil-free infusion of Cy leaves was prepared (Cy extract) and fractionated by column chromatography. Anti-inflammatory properties of Cy extract (1.115 mg/ml) and its PFs, namely phenolic acids (530 μg/ml), flavonoids (97.5 μg/ml) and tannins (78 μg/ml), were investigated using lipopolysaccharide (LPS)-stimulated Raw 264.7 macrophages as in vitro model. As inflammatory parameters, nitric oxide (NO) production was evaluated by Griess reaction, as well as effects on cyclooxygenase-2 (COX-2), inducible NO synthase (iNOS) expression and on intracellular signaling pathways activation, which were analyzed by Western blot using specific antibodies.
  
  
  RESULTS
  Cy extract inhibited iNOS expression, NO production and various LPS-induced pathways like p38 mitogen-activated protein kinase (MAPK), c-jun NH(2)-terminal kinase (JNK) 1/2 and the transcription nuclear factor (NF)-κB. The extracellular signal-regulated kinase (ERK) 1/2 and the phosphatidylinositol-3-kinase (PI3K)/Akt activation were not affected by Cy extract. Both phenolic acid- and tannin-rich fractions significantly inhibited NF-κB activation, iNOS expression and NO production but none of the PFs modulated MAPKs or PI3K/Akt activation. Neither Cy extract nor PFs affected LPS-induced COX-2 expression but LPS-induced PGE(2) production is inhibited by Cy extract and by phenolic acid-rich fraction.
  
  
  CONCLUSIONS
  Our data provide evidence that support the usage of Cymbopogon citratus leaves extract in traditional medicine, and suggest that Cy, in particular its polyphenolic compounds, could constitute a natural source of a new and safe anti-inflammatory drug.
authors.affiliation: Centro de Estudos Farmacêuticos-Faculdade de Farmácia, Universidade de Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548 Coimbra, Portugal.
authors.forename: Vera
authors.initials: V
authors.lastname: Francisco
authors.forename: Artur
authors.initials: A
authors.lastname: Figueirinha
authors.forename: Bruno Miguel
authors.initials: BM
authors.lastname: Neves
authors.forename: Carmen
authors.initials: C
authors.lastname: García-Rodríguez
authors.forename: Maria Celeste
authors.initials: MC
authors.lastname: Lopes
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Cruz
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Batista
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification* / Q000494:pharmacology*; D001681:Biological Assay; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D031743:Cymbopogon / Q000737:chemistry; D015232:Dinoprostone / Q000096:biosynthesis; D020834:Ethnopharmacology; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008519:Medicine, Traditional; D051379:Mice; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D028321:Plant Preparations / Q000302:isolation & purification* / Q000494:pharmacology*; D059808:Polyphenols; D011174:Portugal; D015398:Signal Transduction / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D005419:Flavonoids; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010636:Phenols; D028321:Plant Preparations; D059808:Polyphenols; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D015232:Dinoprostone