title: The influence of seasonality on the content of goyazensolide and on anti-inflammatory and anti-hyperuricemic effects of the ethanolic extract of Lychnophora passerina (Brazilian arnica).
abstract: BACKGROUND
  Lychnophora passerina (Mart ex DC) Gardn (Asteraceae), popularly known as Brazilian arnica, is used in Brazilian folk medicine to treat pain, rheumatism, bruises, inflammatory diseases and insect bites.
  
  
  OBJECTIVE
  Investigate the influence of the seasons on the anti-inflammatory and anti-hyperuricemic activities of ethanolic extract of L. passerina and the ratio of the goyazensolide content, main chemical constituent of the ethanolic extract, with these activities.
  
  
  METHODS
  Ethanolic extracts of aerial parts of L. passerina were obtained from seasons: summer (ES), autumn (EA), winter (EW) and spring (EP). The sesquiterpene lactone goyazensolide, major metabolite, was quantified in ES, EA, EW and EP by a developed and validated HPLC-DAD method. The in vivo anti-hyperuricemic and anti-inflammatory effects of the ethanolic extracts from L. passerina and goyazensolide were assayed on experimental model of oxonate-induced hyperuricemia in mice, liver xanthine oxidase (XOD) inhibition and on carrageenan-induced paw edema in mice.
  
  
  RESULTS
  HPLC method using aqueous solution of acetic acid 0.01% (v/v) and acetonitrile with acetic acid 0.01% (v/v) as a mobile phase in a gradient system, with coumarin as an internal standard and DAD detection at 270nm was developed. The validation parameters showed linearity in a range within 10.0-150.0µg/ml, with intraday and interday precisions a range of 0.61-3.82. The accuracy values of intraday and interday analysis within 87.58-100.95%. EA showed the highest goyazensolide content. From the third to the sixth hour after injection of carrageenan, treatments with all extracts at the dose of 125mg/kg were able to reduce edema. Goyazensolide (10mg/kg) showed significant reduction of paw swelling from the second hour assay. This sesquiterpene lactone was more active than extracts and presented similar effect to indomethacin. Treatments with ES, EA and EP (125mg/kg) and goyazensolide (10mg/kg) reduced serum urate levels compared to hyperuricemic control group and were able to inhibit liver XOD activity. One of the mechanisms by which ES, EA, EP and goyazensolide exercise their anti-hyperuricemic effect is by the inhibition of liver XOD activity. Goyazensolide was identified as the main compound present in ES, EA, EW and EP and it is shown to be one of the chemical constituents responsible for the anti-inflammatory and anti-hyperuricemic effects of the ethanolic extracts.
  
  
  CONCLUSIONS
  The anti-inflammatory and anti-hyperuricemic activities of the ethanolic extracts from L. passerina were not proportionally influenced by the variation of goyazensolide content throughout the seasons. The involvement of goyazensolide on in vivo anti-inflammatory and anti-hyperuricemic activities of L.passerina extracts was confirmed, as well as the possibility of participation of other constituents on these effects. This study demonstrated that the aerial parts of L. passerina may be collected in any season for use as anti-inflammatory agent. For use in hyperuricemia, the best seasons for the collection are summer, autumn and spring. The ethanolic extract of L. passerina and goyazensolide can be considered promising agents in the therapeutic of inflammation, hyperuricemia and gout.
authors.affiliation: Laboratório de Plantas Medicinais (LAPLAMED), CiPharma, Escola de Farmácia, Campus da Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais 35400-000, Brazil.
authors.forename: Bruno César
authors.initials: BC
authors.lastname: de Albuquerque Ugoline
authors.affiliation: Laboratório de Controle de Qualidade, CiPharma, Escola de Farmácia, Campus da Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais 35400-000, Brazil.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: de Souza
authors.affiliation: Laboratório de Plantas Medicinais (LAPLAMED), CiPharma, Escola de Farmácia, Campus da Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais 35400-000, Brazil.
authors.forename: Fernanda Cristina
authors.initials: FC
authors.lastname: Ferrari
authors.affiliation: Laboratório de Plantas Medicinais (LAPLAMED), CiPharma, Escola de Farmácia, Campus da Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais 35400-000, Brazil; Departamento de Química, Instituto Federal de Minas Gerais-Campus Ouro Preto, Ouro Preto, Minas Gerais 35400-000, Brazil.
authors.forename: Zilma Schimith
authors.initials: ZS
authors.lastname: Ferraz-Filha
authors.affiliation: Laboratório de Plantas Medicinais (LAPLAMED), CiPharma, Escola de Farmácia, Campus da Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais 35400-000, Brazil.
authors.forename: Grazielle Brandão
authors.initials: GB
authors.lastname: Coelho
authors.affiliation: Laboratório de Plantas Medicinais (LAPLAMED), CiPharma, Escola de Farmácia, Campus da Universidade Federal de Ouro Preto, Ouro Preto, Minas Gerais 35400-000, Brazil. Electronic address: saudeguima@gmail.com.
authors.forename: Dênia Antunes
authors.initials: DA
authors.lastname: Saúde-Guimarães
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D019659:Asteraceae / Q000737:chemistry*; D001938:Brazil; D001952:Bridged-Ring Compounds / Q000302:isolation & purification / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D004487:Edema / Q000188:drug therapy / Q000473:pathology; D000431:Ethanol / Q000737:chemistry; D005663:Furans / Q000302:isolation & purification / Q000494:pharmacology*; D006073:Gout / Q000188:drug therapy / Q000473:pathology; D006074:Gout Suppressants / Q000302:isolation & purification / Q000494:pharmacology; D033461:Hyperuricemia / Q000188:drug therapy / Q000473:pathology; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008519:Medicine, Traditional; D051379:Mice; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000494:pharmacology*; D012621:Seasons; D054830:Sesterterpenes; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
chemical_list: D000893:Anti-Inflammatory Agents; D001952:Bridged-Ring Compounds; D005663:Furans; D006074:Gout Suppressants; D010936:Plant Extracts; D054830:Sesterterpenes; C499803:furanoheliangolide; D000431:Ethanol; D014969:Xanthine Oxidase; D007213:Indomethacin
keywords: Gout; Hyperuricemia; Inflammation; Lychnophora passerina; Seasonality