R McKinnon1, M Binder2, I Zupkó3, T Afonyushkin2, I Lajter4, A Vasas4, R de Martin2, C Unger5, H Dolznig5, R Diaz6, R Frisch6, C M Passreiter7, G Krupitza8, J Hohmann4, B Kopp9, V N Bochkov2. 1. Department of Pharmacognosy, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria. Electronic address: ruxandra.mckinnon@univie.ac.at. 2. Department of Vascular Biology and Thrombosis Research, Center of Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, A-1090 Vienna, Austria. 3. Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary. 4. Department of Pharmacognosy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary. 5. Institute of Medical Genetics, Medical University of Vienna, Währinger Strasse 10, A-1090 Vienna, Austria. 6. Institute of Ethnobiology, Playa Diana, San José/Petén, Guatemala. 7. Institute of Pharmaceutical Biology and Biotechnology, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, D-40225 Düsseldorf, Germany. 8. Clinical Institute of Pathology, Medical University of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria. 9. Department of Pharmacognosy, University of Vienna, Althanstraße 14, A-1090 Vienna, Austria.
Abstract
PURPOSE: 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.
PURPOSE: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: Adolfo Andrade-Cetto; Elda Carola Cruz; Christian Alan Cabello-Hernández; René Cárdenas-Vázquez Journal: Evid Based Complement Alternat Med Date: 2019-01-01 Impact factor: 2.629