Industrial Crops and Products 47 (2013) 270–276 Contents lists available at SciVerse ScienceDirect Industrial Crops and Products journa l h om epa ge: www.elsevier.com/locate/indcrop Genetical, developmental and spatial factors influencing parthenolide and its precursor costunolide in feverfew (Tanacetum parthenium L. Schulz Bip.) Mohammad Majdi a,c,* , Tatsiana Charnikhova b , Harro Bouwmeester b a Agricultural Biotechnology Department, Faculty of Agriculture, University of Kurdistan, Sanandaj, Iran b Laboratory of Plant Physiology, Wageningen University, P.O. Box 658, Wageningen, The Netherlands c Research Center for Medicinal Plant Breeding and Development, University of Kurdistan, Sanandaj, Iran a r t i c l e i n f o Article history: Received 17 October 2012 Received in revised form 12 March 2013 Accepted 19 March 2013 Keywords: Tanacetum parthenium Medicinal plant Parthenolide Costunolide Secondary metabolites a b s t r a c t Feverfew (Tanacetum parthenium) is a medicinal herb which is rich in sesquiterpene lactones. The main sesquiterpene lactone in feverfew is parthenolide. Costunolide has been considered to be the immediate precursor of parthenolide. Parthenolide and costunolide levels in flowers and in leaves collected during the vegetative and generative phase of three feverfew genotypes (diploid, tetraploid and Zardband cv.) and in 2,4-D treated leaves of the diploid genotype were analyzed using UPLC–MS/MS. Parthenolide and costunolide levels showed a similar pattern in all genotypes, and were higher in flowers than in leaves. The developmental pattern of these two compounds was not the same in flowers of the different genotypes and 2,4-D treatment increased both coordinately. In conclusion, we show that genetical, developmental and spatial factors all influence the composition of sesquiterpene lactones in feverfew. © 2013 Elsevier B.V. All rights reserved. 1. Introduction Plants are a major source of a large number of medicinally important compounds (Verpoorte et al., 2006). The quality and quantity of secondary metabolites can be affected by several factors e.g. plant species, genotypes, developmental stages and environ- ment factors (Goossens et al., 2003; Houshyani et al., 2011; Jessing et al., 2013). It has been well documented in many plant species that the secondary metabolite level and composition are highly vari- able due to multiple factors (Masaroviˇ cová et al., 2010). Terpenes are the largest and most diverse group of secondary metabolites with more than 20,000 compounds, having many diverse ecologi- cal functions in plants (Davis and Croteau, 2000). They have been extensively used as pharmaceuticals, flavors, fragrances and dyes (Misawa, 2011). Sesquiterpene lactones comprise the largest class of terpenes and have been mostly reported in the Asteraceae with more than 4000 different compounds that arise from different Abbreviations: MVA, mevalonic acid; UPLC, ultra performance liquid chromatog- raphy; MS, mass spectrometry; MRM, multiple reaction monitoring; PDA, photo diode array; RT, retention time; IS, internal standard. * Corresponding author at: Agricultural Biotechnology Department, Faculty of Agriculture, University of Kurdistan, Sanandaj, Iran. Tel.: +98 8716620553; fax: +98 8716620553. E-mail addresses: m.majdi@uok.ac.ir, majdi60@gmail.com (M. Majdi). sesquiterpene skeletons including germacranolides, eudesmano- lides and guaianolides. Costunolide has been postulated to be the parent compound of these three types of sesquiterpene lactones (Fig. 1) (de Kraker et al., 2002). Feverfew (Tanacetum parthenium L. Schulz Bip.) is a diploid (2n = 2x = 18) and perennial medicinal herb belonging to the Asteraceae that traditionally has been used as a fever-reducer and to treat headaches (Palevitch et al., 1997). Chro- mosome doubling in feverfew via colchicine treatment has been successfully conducted and resulted in the production of viable tetraploid feverfew (2n = 4x = 36) plants with good survival and growth performance (Majdi et al., 2010). The predominant con- stituent and effective compound in feverfew is parthenolide (Fig. 1), which raised considerable attention due to its medicinal value and pharmacological activities that have been investigated through in vivo and in vitro experiments (Zhou et al., 2008; Cheng and Xie, 2011). The migraine prophylactic property of feverfew has also been attributed to parthenolide, which inhibits the serotenin, 5- hydroxytryptamine release from blood platelets and blocks the transcription factor nuclear factor-kappaB (NF-B) that mediate the pain and inflammatory responses (Sohma et al., 2011). Parthenolide has a sesquitepene lactone structure which is most likely synthesized through the mevalonic acid (MVA) path- way (de Kraker et al., 2002). Parthenolide has been postulated to be derived from costunolide, by the introduction of an epoxide at the C 4 –C 5 position (Fig. 1) (Majdi et al., 2011). The level of parthenolide in feverfew depends on different factors e.g. 0926-6690/$ – see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.indcrop.2013.03.021