@article{kaur_oberhofer_juzumaite_raja_gulledge_kao_faeth_laster_oberlies_cech_2016, title={Secondary metabolites from fungal endophytes of Echinacea purpurea suppress cytokine secretion by macrophage-type cells}, volume={11}, DOI={10.1177/1934578x1601100827}, abstractNote={Botanical extracts of Echinacea purpurea have been widely used for the treatment of upper respiratory infections. We sought to chemically examine fungal endophytes inhabiting E. purpurea, and to identify compounds produced by these endophytes with in vitro cytokine-suppressive activity. Twelve isolates from surface sterilized seeds of E. purpurea were subjected to fractionation and major components were isolated. Sixteen secondary metabolites belonging to different structural classes were identified from these isolates based on NMR and mass spectrometry data. The compounds were tested for their influence on cytokine secretion by murine macrophage-type cells. Alternariol (1), O-prenylporriolide (4), porritoxin (10) β-zearalenol (13), and ( S)-zearalenone (14) inhibited production of TNF-α from RAW 264.7 macrophages stimulated with LPS in the absence of any significant cytotoxicity. This is the first report of a cytokine-suppressive effect for 4. The results of this study are particularly interesting given that they show the presence of compounds with cytokine-suppressive activity in endophytes from a botanical used to treat inflammation. Future investigations into the role of fungal endophytes in the biological activity of E. purpurea dietary supplements may be warranted.}, number={8}, journal={Natural Product Communications}, author={Kaur, A. and Oberhofer, M. and Juzumaite, M. and Raja, H. A. and Gulledge, T. V. and Kao, D. N. and Faeth, S. H. and Laster, S. M. and Oberlies, N. H. and Cech, N. B.}, year={2016}, pages={1143–1146} }
 @article{todd_gulledge_britton_oberhofer_leyte-lugo_moody_shymanovich_grubbs_juzumaite_graf_et al._2015, title={Ethanolic Echinacea purpurea Extracts Contain a Mixture of Cytokine-Suppressive and Cytokine-Inducing Compounds, Including Some That Originate from Endophytic Bacteria}, volume={10}, ISSN={["1932-6203"]}, DOI={10.1371/journal.pone.0124276}, abstractNote={Echinacea preparations, which are used for the prevention and treatment of upper respiratory infections, account for 10% of the dietary supplement market in the U.S., with sales totaling more than $100 million annually. In an attempt to shed light on Echinacea's mechanism of action, we evaluated the effects of a 75% ethanolic root extract of Echinacea purpurea, prepared in accord with industry methods, on cytokine and chemokine production from RAW 264.7 macrophage-like cells. We found that the extract displayed dual activities; the extract could itself stimulate production of the cytokine TNF-α, and also suppress production of TNF-α in response to stimulation with exogenous LPS. Liquid:liquid partitioning followed by normal-phase flash chromatography resulted in separation of the stimulatory and inhibitory activities into different fractions, confirming the complex nature of this extract. We also studied the role of alkylamides in the suppressive activity of this E. purpurea extract. Our fractionation method concentrated the alkylamides into a single fraction, which suppressed production of TNF-α, CCL3, and CCL5; however fractions that did not contain detectable alkylamides also displayed similar suppressive effects. Alkylamides, therefore, likely contribute to the suppressive activity of the extract but are not solely responsible for that activity. From the fractions without detectable alkylamides, we purified xanthienopyran, a compound not previously known to be a constituent of the Echinacea genus. Xanthienopyran suppressed production of TNF-α suggesting that it may contribute to the suppressive activity of the crude ethanolic extract. Finally, we show that ethanolic extracts prepared from E. purpurea plants grown under sterile conditions and from sterilized seeds, do not contain LPS and do not stimulate macrophage production of TNF-α, supporting the hypothesis that the macrophage-stimulating activity in E. purpurea extracts can originate from endophytic bacteria. Together, our findings indicate that ethanolic E. purpurea extracts contain multiple constituents that differentially regulate cytokine production by macrophages.}, number={5}, journal={PLOS ONE}, author={Todd, Daniel A. and Gulledge, Travis V. and Britton, Emily R. and Oberhofer, Martina and Leyte-Lugo, Martha and Moody, Ashley N. and Shymanovich, Tatsiana and Grubbs, Laura F. and Juzumaite, Monika and Graf, Tyler N. and et al.}, year={2015}, month={May} }
 @article{moazami_gulledge_laster_pierce_2015, title={Synthesis and biological evaluation of a series of fatty acid amides from Echinacea}, volume={25}, ISSN={["1464-3405"]}, DOI={10.1016/j.bmcl.2015.06.024}, abstractNote={Alkylamides are lipophilic constituents of Echinacea and possess numerous biological activities. Although significant effort has been focused on the study of crude Echinacea extracts, very little is known regarding the activities of the individual constituents that make up these herbal treatments. Herein we explore the SAR of simple alkylamides found in Echinacea extracts with respect to their ability to decrease the production of the pro-inflammatory mediator TNF-α. Our results have revealed the key structural requirements for activity and provide lead compounds for further investigation of these poorly understood molecules.}, number={16}, journal={BIOORGANIC & MEDICINAL CHEMISTRY LETTERS}, author={Moazami, Yasamin and Gulledge, Travis V. and Laster, Scott M. and Pierce, Joshua G.}, year={2015}, month={Aug}, pages={3091–3094} }