title: Anti-inflammatory activity of Eupatorium perfoliatum L. extracts, eupafolin, and dimeric guaianolide via iNOS inhibitory activity and modulation of inflammation-related cytokines and chemokines.
abstract: BACKGROUND
  Eupatorium perfoliatum L. has been used traditionally for the treatment of fever, malaria and inflammation-associated diseases. Nowadays it is mostly used as immune activating remedy. The following study was performed to evaluate extracts with different polarity and defined lead-compounds from the herbal material on potential in vitro activities concerning immune cell activation, phagocytosis, and inflammation-related processes.
  
  
  METHODS
  MeOH-, EtOH-, and DCM extracts, beside several subfractions and isolated polysaccharides, sesquiterpene lactones and flavonoids were prepared and characterized analytically from the aerial parts of E. perfoliatum. Immunological activity was tested within lymphocyte transformation test on PBMC, test on enhancement of phagocytosis and of NO-production by murine RAW 264.7 macrophages. Anti-inflammatory effects were assessed from LPS-stimulated RAW 264.7 cells by NO/iNOS quantification, gene array, real-time PCR and ELISA.
  
  
  RESULTS
  No stimulatory activity was found within lymphocyte transformation test, for phagocytic activity and NO formation in macrophages. MeOH-, EtOH- and DCM extracts showed anti-inflammatory activity against LPS-stimulated macrophages by inhibition of NO release (IC(50)>100, 89, 19 μg/mL resp.) with eupafolin and a dimeric guaianolide having prominent NO inhibiting activity (IC(50) 6 resp. 16 μM). Anti-inflammatory activity was found on gene and protein level by significant down-regulation of cytokines CSF-3, IL-1α, IL-1β, and chemokines CCL2, CCL22 and CXCL10. Also TNF was down-regulated moderately (-17%).
  
  
  CONCLUSIONS
  Although the postulated immunostimulating properties of E. perfoliatum have not been confirmed, the anti-inflammatory effects can be seen as a verification of the traditional use against inflammatory diseases.
authors.affiliation: University of Münster, Institute for Pharmaceutical Biology and Phytochemistry, Hittorfstraße 56, D-48149 Münster, Germany.
authors.forename: Mareike
authors.initials: M
authors.lastname: Maas
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Deters
authors.forename: Andreas
authors.initials: A
authors.lastname: Hensel
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D018925:Chemokines / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D000431:Ethanol / Q000737:chemistry; D036602:Eupatorium / Q000737:chemistry; D047309:Flavones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D000432:Methanol / Q000737:chemistry; D008752:Methylene Chloride / Q000737:chemistry; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010587:Phagocytosis / Q000187:drug effects; D035261:Plant Components, Aerial; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045789:Sesquiterpenes, Guaiane / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D012997:Solvents / Q000737:chemistry
chemical_list: D000893:Anti-Inflammatory Agents; D018925:Chemokines; D016207:Cytokines; D004791:Enzyme Inhibitors; D047309:Flavones; D018836:Inflammation Mediators; D010936:Plant Extracts; D045789:Sesquiterpenes, Guaiane; D012997:Solvents; D009569:Nitric Oxide; D000431:Ethanol; D008752:Methylene Chloride; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C503624:eupafolin; D000432:Methanol