title: Pharmacological insight into the anti-inflammatory activity of sesquiterpene lactones from Neurolaena lobata (L.) R.Br. ex Cass.
abstract: OBJECTIVE
  Neurolaena lobata is a Caribbean medicinal plant used for the treatment of several conditions including inflammation. Recent data regarding potent anti-inflammatory activity of the plant and isolated sesquiterpene lactones raised our interest in further pharmacological studies. The present work aimed at providing a mechanistic insight into the anti-inflammatory activity of N. lobata and eight isolated sesquiterpene lactones, as well as a structure-activity relationship and in vivo anti-inflammatory data.
  
  
  METHODS
  The effect of the extract and its compounds on the generation of pro-inflammatory proteins was assessed in vitro in endothelial and monocytic cells by enzyme-linked immunosorbent assay. Their potential to modulate the expression of inflammatory genes was further studied at the mRNA level. In vivo anti-inflammatory activity of the chemically characterized extract was evaluated using carrageenan-induced paw edema model in rats.
  
  
  RESULTS
  The compounds and extract inhibited LPS- and TNF-α-induced upregulation of the pro-inflammatory molecules E-selectin and interleukin-8 in HUVECtert and THP-1 cells. LPS-induced elevation of mRNA encoding for E-selectin and interleukin-8 was also suppressed. Furthermore, the extract inhibited the development of acute inflammation in rats.
  
  
  CONCLUSIONS
  Sesquiterpene lactones from N. lobata interfered with the induction of inflammatory cell adhesion molecules and chemokines in cells stimulated with bacterial products and cytokines. Structure-activity analysis revealed the importance of the double bond at C-4-C-5 and C-2-C-3 and the acetyl group at C-9 for the anti-inflammatory activity. The effect was confirmed in vivo, which raises further interest in the therapeutic potential of the compounds for the treatment of inflammatory diseases.
authors.affiliation: Department of Pharmacognosy, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria. Electronic address: ruxandra.mckinnon@univie.ac.at.
authors.forename: R
authors.initials: R
authors.lastname: McKinnon
authors.affiliation: Department of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, A-1090 Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Binder
authors.affiliation: Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
authors.forename: I
authors.initials: I
authors.lastname: Zupkó
authors.affiliation: Department of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, A-1090 Vienna, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Afonyushkin
authors.affiliation: Department of Pharmacognosy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
authors.forename: I
authors.initials: I
authors.lastname: Lajter
authors.affiliation: Department of Pharmacognosy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Vasas
authors.affiliation: Department of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, A-1090 Vienna, Austria.
authors.forename: R
authors.initials: R
authors.lastname: de Martin
authors.affiliation: Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, A-1090 Vienna, Austria.
authors.forename: C
authors.initials: C
authors.lastname: Unger
authors.affiliation: Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, A-1090 Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Dolznig
authors.affiliation: Institute of Ethnobiology, Playa Diana, San José/Petén, Guatemala.
authors.forename: R
authors.initials: R
authors.lastname: Diaz
authors.affiliation: Institute of Ethnobiology, Playa Diana, San José/Petén, Guatemala.
authors.forename: R
authors.initials: R
authors.lastname: Frisch
authors.affiliation: Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, D-40225 Düsseldorf, Germany.
authors.forename: C M
authors.initials: CM
authors.lastname: Passreiter
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Krupitza
authors.affiliation: Department of Pharmacognosy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Hohmann
authors.affiliation: Department of Pharmacognosy, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria.
authors.forename: B
authors.initials: B
authors.lastname: Kopp
authors.affiliation: Department of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, A-1090 Vienna, Austria.
authors.forename: V N
authors.initials: VN
authors.lastname: Bochkov
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D019659:Asteraceae / Q000737:chemistry*; D019040:E-Selectin / Q000378:metabolism; D004487:Edema / Q000188:drug therapy; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D015394:Molecular Structure; D009000:Monocytes / Q000187:drug effects; D035261:Plant Components, Aerial / Q000737:chemistry; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; C508606:CXCL8 protein, human; D019040:E-Selectin; D016209:Interleukin-8; D007783:Lactones; C546936:SELE protein, human; D012717:Sesquiterpenes
keywords: Anti-inflammatory; Chemokines; Natural products; Neurolaena lobata; Sesquiterpene lactones