title: In vitro and in vivo assessment of meadowsweet (Filipendula ulmaria) as anti-inflammatory agent.
abstract: BACKGROUND
  Meadowsweet (Filipendula ulmaria (L.) Maxim, Rosaceae) has been traditionally used in most European countries for the treatment of inflammatory diseases due to its antipyretic, analgesic, astringent, and anti-rheumatic properties. However, there is little scientific evidence on F. ulmaria anti-inflammatory effects regarding its impact on cyclooxygenases enzymatic activity and in vivo assessment of anti-inflammatory potential. This study aims to reveal the anti-inflammatory activity of methanolic extracts from the aerial parts (FUA) and roots (FUR) of F. ulmaria, both in in vitro and in vivo conditions.
  
  
  METHODS
  The characteristic phenolic compounds in F. ulmaria extracts were monitored via high performance thin layer chromatography (HPTLC). The in vitro anti-inflammatory activity of F. ulmaria extracts was evaluated using cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzyme assays, and an assay for determining COX-2 gene expression. The in vivo anti-inflammatory effect of F. ulmaria extracts was determined in two doses (100 and 200 mg/kg b.w.) with hot plate test and carrageenan-induced paw edema test in rats. Inflammation was also evaluated by histopathological and immunohistochemical analysis.
  
  
  RESULTS
  FUA extract showed the presence of rutoside, spiraeoside, and isoquercitrin. Both F. ulmaria extracts at a concentration of 50μg/mL were able to inhibit COX-1 and -2 enzyme activities, whereby FUA extract (62.84% and 46.43% inhibition, respectively) was double as effective as the root extract (32.11% and 20.20%, respectively). Extracts hardly inhibited the level of COX-2 gene expression in THP-1 cells at a concentration of 25μg/mL (10.19% inhibition by FUA and 8.54% by FUR). In the hot plate test, both extracts in two doses (100 and 200mg/kg b.w.), exhibited an increase in latency time when compared with the control group (p<0.05). In the carrageenan-induced acute inflammation test, FUA at doses of 100 and 200mg/kg b.w., and FUR at 200mg/kg, were able to significantly reduce the mean maximal swelling of rat paw until 6h of treatment. Indomethacin, FUA, and FUR extracts significantly decreased inflammation score and this effect was more pronounced after 24h, compared to the control group (p<0.05).
  
  
  CONCLUSIONS
  The observed results of in vitro and, for the first time, in vivo anti-inflammatory activity of meadowsweet extracts, provide support of the traditional use of this plant in the treatment of different inflammatory conditions. Further investigation of the anti-inflammatory compounds could reveal the mechanism of anti-inflammatory action of these extracts.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, 34000 Kragujevac, Serbia. Electronic address: jkatanic@kg.ac.rs.
authors.forename: Jelena
authors.initials: J
authors.lastname: Katanić
authors.affiliation: Department of Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, 34000 Kragujevac, Serbia.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Boroja
authors.affiliation: Department of Chemistry, Faculty of Science, University of Kragujevac, Radoja Domanovića 12, 34000 Kragujevac, Serbia.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Mihailović
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitaetsplatz 4, 8010 Graz, Austria.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Nikles
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitaetsplatz 4, 8010 Graz, Austria.
authors.forename: San-Po
authors.initials: SP
authors.lastname: Pan
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, 34000 Kragujevac, Serbia.
authors.forename: Gvozden
authors.initials: G
authors.lastname: Rosić
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, 34000 Kragujevac, Serbia.
authors.forename: Dragica
authors.initials: D
authors.lastname: Selaković
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, 34000 Kragujevac, Serbia.
authors.forename: Jovana
authors.initials: J
authors.lastname: Joksimović
authors.affiliation: Department of Pathology, Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovića 69, 34000 Kragujevac, Serbia.
authors.forename: Slobodanka
authors.initials: S
authors.lastname: Mitrović
authors.affiliation: Institute of Pharmaceutical Sciences, Department of Pharmacognosy, University of Graz, Universitaetsplatz 4, 8010 Graz, Austria.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Bauer
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy; D020834:Ethnopharmacology; D031984:Filipendula / Q000737:chemistry*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008297:Male; D059226:Nociceptive Pain / Q000188:drug therapy; D035261:Plant Components, Aerial / Q000737:chemistry; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D018517:Plant Roots / Q000737:chemistry; D017208:Rats, Wistar
chemical_list: D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D010936:Plant Extracts; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2
keywords: Carrageenan-induced edema; Cyclooxygenase; Filipendula ulmaria; Hot plate test; Inflammation; NS-398 (PubChem CID: 4553); apigenin (PubChem CID: 5280443); dexamethasone (PubChem CID: 5743); hyperoside (PubChem CID: 5281643); indomethacin (PubChem CID: 3715); isoquercitrin (PubChem CID: 5280804); quercetin (PubChem CID: 5280343); rutoside (PubChem CID: 5280805); spiraeoside (PubChem CID: 5320844); λ-carrageenan (PubChem CID: 91972149)