Potent anti-inflammatory activity of sesquiterpene lactones from Neurolaena lobata (L.) R. Br. ex Cass., a Q’eqchi’ Maya traditional medicine Brendan Walshe-Roussel a,1 , Christine Choueiri b,1 , Ammar Saleem a , Muhammd Asim b , Federico Caal c , Victor Cal c , Marco Otarola Rojas d , Todd Pesek e , Tony Durst b , John Thor Arnason a,⇑ a Centre for Research in Biotechnology and Biopharmaceuticals, Department of Biology, University of Ottawa, Ottawa, ON, Canada K1N 6N5 b Department of Chemistry, University of Ottawa, Ottawa, ON, Canada K1N 6N5 c Belize Indigenous Training Institute, Punta Gorda, Toledo District, Belize d Herbario Juvenal Valerio Rodriguez, Universidad Nacional, Heredia, Costa Rica e Department of Health Sciences, Center for Healing Across Cultures, Cleveland State University, Cleveland, OH 44115, USA article info Article history: Received 25 December 2012 Received in revised form 15 March 2013 Accepted 8 May 2013 Available online 5 June 2013 Keywords: Neurolaena lobata Asteraceae Sesquiterpene lactones Neurolenin Lobatin Parthenolide Anti-inflammatory TNF-a Traditional medicine abstract The widespread use of Neurolaena lobata (L.) R. Br. ex Cass. by Q’eqchi’ Maya and indigenous healers throughout the Caribbean for inflammatory conditions prompted the study of the anti-inflammatory activity of this traditional medicine. The objectives of this study were to conduct a detailed ethnobotan- ical investigation of the uses of N. lobata by the Q’eqchi’ Maya of Belize for a variety of inflammatory symptoms and to evaluate the in vitro anti-inflammatory activity of leaf extract and isolated sesquiter- pene lactones. The crude 80% EtOH extract of N. lobata leaves administered at 100 lg/mL reduced LPS- stimulated TNF-a production in THP-1 monocytes by 72% relative to the stimulated vehicle control. Iso- lated sesquiterpene lactones, neurolenins B, C + D, lobatin B and 9a-hydroxy-8b-isovalerianyloxy-calycu- latolide were more active (IC 50 = 0.17–2.32 lM) than the positive control parthenolide (IC 50 = 4.79 lM). The results provide a pharmacological and phytochemical basis for the traditional use of this leaf for inflammatory conditions. Ó 2013 Elsevier Ltd. All rights reserved. 1. Introduction Neurolaena lobata (L.) R. Br. ex Cass. (Asteraceae) is a common medicinal plant found growing in open areas throughout Central America, the Caribbean, and into southern Mexico (Turner, 1982). The bitter tasting leaves of the plant are widely used by indigenous traditional healers in these regions to treat a variety of ailments including malaria, diabetes, skin diseases and cancer (Giron et al., 1991; Hartwell, 1968; Morton, 1981). Among Yucatec Maya, the crushed leaf is used to treat itchy inflamed skin (Arnason et al., 1980). Arvigo and Balick (1993) described a variety of conditions treated with the plant, including ringworm, wounds, sores, and infections, by Mopan Maya and other cultures. A general ethnobo- tanical survey of medicinal plant use among the Q’eqchi’ Maya healers of southern Belize established that the leaves of N. lobata are used to treat fevers and malaria, as well as diarrhea, ulcers and diabetes (Amiguet et al., 2005). It is known locally by such names as Jackass Bitters (English Creole), Mano de lagarto and Tres puntas (Spanish), Kayabim (Yucatec and Mopan Maya) and K’a mank (Q’eqchi’ Maya). Previous phytochemical studies have identified 11 sesquiter- pene lactones (Borges-Del-Castillo et al., 1982; Manchand and Blount, 1978; Passreiter et al., 1995) and 12 flavonoids in the leaves (Kerr et al., 1981), and several thymol derivatives in the roots of N. lobata (Bohlmann et al., 1979). Manchand and Blount (1978) were the first to isolate the germacranolide sesquiterpene lactones neurolenins A and B (1) from the leaves of plants collected in Trinidad. In leaves of N. lobata collected in Panama, Borges-Del- Castillo et al. (1982) isolated neurolenin B (1), and identified two novel furanoheliangolide sesquiterpene lactones, lobatins A and B (4). Further work by Passreiter et al. (1995) identified an additional 7 sesquiterpene lactones from the leaves of plants collected in Gua- temala. These include 4 germacranolide sesquiterpene lactones, neurolenins C (2) and D (3), and trace amounts of E and F, as well as 3 furanoheliangolide sesquiterpene lactones, lobatin C in trace 0031-9422/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.phytochem.2013.05.004 ⇑ Corresponding author. Address: Department of Biology, University of Ottawa, Ottawa, ON, Canada K1N 6N5. Tel.: +1 613 562 5262; fax: +1 613 562 5765. E-mail address: John.Arnason@uOttawa.ca (J.T. Arnason). 1 These authors contributed equally to this work. Phytochemistry 92 (2013) 122–127 Contents lists available at SciVerse ScienceDirect Phytochemistry journal homepage: www.elsevier.com/locate/phytochem