Caffeic acid derivatives isolated from the aerial parts of Galinsoga parviﬂora and their effect on inhibiting oxidative burst in human neutrophils Marta K. Dudek b,c , Lukasz Dudkowski a , Agnieszka Bazylko a , Slawomir Ka  zmierski b , Anna K. Kiss a, * a Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland b Centre of Molecular and Macromolecular Studies PAS, Sienkiewicza 112, 90-363 Lodz, Poland c Physical Chemistry Department, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland A R T I C L E I N F O Article history: Received 16 January 2016 Received in revised form 3 May 2016 Accepted 17 May 2016 Available online xxx Keywords: Galinsoga parviﬂora Caffeoylglucaric acid derivatives Caffeoylaltraric acid derivatives J-couplings analysis Oxidative burst A B S T R A C T Four new caffeoyl -glucaric and -altraric acid derivatives along with eleven known compounds were isolated from aerial parts of Galinsonga parviﬂora. Their structures were elucidated by high-resolution spectroscopic studies. The four new compounds were determined as being 2,3,4,5-tetracaffeoylglucaric acid (1), 2,4,5-tricaffeoylglucaric acid (2), 2,3,4- or 3,4,5-tricaffeoylaltraric acid (3) and 2,3(4,5)- dicaffeoylaltraric acid (4). A reliable criterion for the determination of the linkage position of caffeic acids moieties in glucaric acid derivatives has been proposed, on the basis of detailed analysis of the respective J-couplings, including substitution and solvent inﬂuence on the observed values. All hexaric acids derivatives appeared as inhibitors of reactive oxygen species production by stimulated neutrophils. ã 2016 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved. 1. Introduction Galinsoga parviﬂora Cav. (Asteraceae) was brought to Europe from Central and South America. At ﬁrst it was planted in botanical gardens, but it very quickly spread to become a common weed. G. parviﬂora also known as gallant soldier is recognized as an edible plant: in Zimbabwe and Tanzania young leaves and shoots are cooked as vegetables (Maroyi, 2013; Damalas, 2008), as well as in South Africa (Odhav et al., 2007). Young plants/leaves in North and Latin America may be used fresh in salads or for preparing soups (Medve and Medve, 2000; Damalas, 2008). This suggests the plant material is non-toxic and safe for human consumption. The G. parviﬂora herb has been used in the traditional medicine of America, Asia, Africa and Europe. In Brazil water extracts are drunk in order to cure ﬂu and colds (Agra et al., 2007; Oliveira et al., 2012) and applied to heal wounds (Schmidt et al., 2009); in Ecuador infusions are used in to treat fever and internal inﬂammation (Tene et al., 2007); and in India for rheumatism (Gairola et al., 2014). In the traditional medicine of Uganda, G. parviﬂora is used to treat bleeding (Hamill et al., 2000), while in Kenya extracts from the stems and leaves are used to treat colds and sores (Matu and Van Staden, 2003); in Ethiopia preparation from ﬂowers are applied to the gum in case of toothache (Tolossa et al., 2013). In Europe, especially in Poland the aerial parts of the plant are traditionally used externally in the treatment of skin problems, dermatological diseases, eczemas, lichens and hard healing wounds (Strzelecka and Kowalski, 2000). Such uses were partially explained in in-vitro studies  recent research on Brazilian medicinal plants has shown that extracts from the leaves of G. parviﬂora can accelerate wound healing in a scratch assay (Schmidt et al., 2009) while hydrophilic extracts from aerial parts exhibited protective effects against damage caused by UV irradiation (Bazylko et al., 2015a,b). Extracts (methanolic and aqueous) from the stems and the leaves of G. parviﬂora inhibited the cyclooxygenase 1–COX1 activity by 90% and 54% respectively, but at a high concentration of 500 mg/mL (Matu and Van Staden, 2003), while the IC 50 for the 5-lipoxygenase (5- LOX) was signiﬁcantly lower with a value of 30.7 mg/mL for the methanolic extract (Akula and Odhav, 2008). The antioxidant activity of the plant extracts was also reported in a previous study, but the observed activity was associated only with the total amount of phenolic compounds (Bazylko et al., 2015b; Akula and Odhav, 2008; Bazylko et al., 2012; Chanaj-Kaczmarek et al., 2015). Although leaves or aerial parts obtained from gallant soldier are used in folk medicine, their chemical composition has only been * Corresponding author. E-mail address: akiss@wum.edu.pl (A.K. Kiss). http://dx.doi.org/10.1016/j.phytol.2016.05.007 1874-3900/ã 2016 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved. Phytochemistry Letters 16 (2016) 303–310 Contents lists available at ScienceDirect Phytochemistry Letters journa l home page : www.e lsevier.com/loca te/phyt ol