title: Chlorogenic acids from Tithonia diversifolia demonstrate better anti-inflammatory effect than indomethacin and its sesquiterpene lactones.
abstract: BACKGROUND
  T. diversifolia (Hemsl.) A. Gray (Asteraceae) has been used in the traditional medicine in several countries as anti-inflammatory and against other illnesses. It is important to evaluate the anti-inflammatory activity of extracts from the leaves of this species, including an infusion, to identify the main constituents of the extracts, observe their effects and correlate them with the anti-inflammatory activity.
  
  
  METHODS
  An infusion, a leaf rinse extract (LRE) and a polar extract from the rinsed leaves (PE) were obtained and analysed by HPLC-UV-DAD and infrared spectroscopy. The major compounds of these extracts were quantified. The three obtained extracts were evaluated for their anti-inflammatory activities using the paw oedema and croton oil ear oedema assays in mice. Furthermore, neutrophil migration was measured by evaluating myeloperoxidase activity.
  
  
  RESULTS
  The PE consists primarily of chlorogenic acids (CAs) and lacks sesquiterpene lactones (STLs). The LRE is rich in STLs and includes a few flavonoids. The infusion is chemically similar to the PE but also contains very low amounts of STLs. The PE and LRE have better mechanisms of action than non-steroidal anti-inflammatory drugs (NSAIDs). Unlike NSAIDs, both the PE and LRE inhibit oedema and neutrophil migration. The pool of CAs from the PE of T. diversifolia has an additional mechanism of action, and its anti-inflammatory effect was greater than what is described in the literature for this class of compounds using the same evaluation models. The similar chemical compositions observed for the infusion and the PE, contrasted with the different activities observed, suggests the presence of antagonist compounds produced during the extraction procedure (infusion); the infusion did not inhibit oedema, however it inhibited neutrophil migration. It suggests that although the great majority of plants present CAs, the category of anti-inflammatory effect of their extracts depends on a suitable pool of compounds and an absence of antagonists, among other factors.
  
  
  CONCLUSIONS
  CAs from T. diversifolia comprise a good pool of anti-inflammatory compounds with better activity mechanisms than NSAIDs, other active compounds from the leaf extracts (STLs and flavonoids) and CAs from other plant sources. Thus, the PE of T. diversifolia has high potential for the development of new anti-inflammatory phytomedicines. The infusion probably contains antagonists, and therefore it can be useful to treat inflammation processes where neutrophil recruitment is involved and oedema is not.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP), Universidade de São Paulo (USP), Departamento de Ciências Farmacêuticas. Av. Café s/no., Monte Alegre, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Daniela Aparecida
authors.initials: DA
authors.lastname: Chagas-Paula
authors.forename: Rejane Barbosa de
authors.initials: RB
authors.lastname: Oliveira
authors.forename: Vanessa Cristina
authors.initials: VC
authors.lastname: da Silva
authors.forename: Leonardo
authors.initials: L
authors.lastname: Gobbo-Neto
authors.forename: Thaís Helena
authors.initials: TH
authors.lastname: Gasparoto
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Campanelli
authors.forename: Lúcia Helena
authors.initials: LH
authors.lastname: Faccioli
authors.forename: Fernando Batista
authors.initials: FB
authors.lastname: Da Costa
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D019659:Asteraceae / Q000737:chemistry*; D002726:Chlorogenic Acid / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D003509:Cyclohexanecarboxylic Acids / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D004487:Edema / Q000188:drug therapy*; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D007783:Lactones / Q000494:pharmacology; D051379:Mice; D020556:Neutrophil Infiltration / Q000187:drug effects; D008517:Phytotherapy; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D018515:Plant Leaves; D012717:Sesquiterpenes / Q000494:pharmacology
chemical_list: D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003509:Cyclohexanecarboxylic Acids; D007783:Lactones; D010936:Plant Extracts; D012717:Sesquiterpenes; D002726:Chlorogenic Acid; D007213:Indomethacin