Scorzonera species are used in different folk medicines to combat many diseases, including the illnesses connected with inflammation. Previous experiments showed anti-inflammatory activity of Scorzonera extracts in vivo. S. latifolia, S. cana var. jacquiniana, S. tomentosa, S. mollis ssp. szowitsii, S. eriophora, S. incisa, S. cinerea, and S. parviflora extracts were, therefore, evaluated for their inhibitory activities of TNF-α and IL-1β production, and NF-κB nuclear translocation in THP-1 macrophages. The HPLC analysis was carried out to elucidate and to compare the composition of these extracts. Major compounds of the tested extracts have been isolated using different chromatographic techniques and further tested for their inhibitory activities on TNF-α and IL-1β production. Several extracts showed promising anti-inflammatory activity in these in vitro tests. Results of HPLC analysis revealed chlorogenic acid as a compound present in all tested extracts. Hyperoside, quercetin-3-O-β-d-glucoside and rutin were also present in varying amount in some Scorzonera species analyzed. Furthermore, eight phenolics which were identified as quercetin-3-O-β-d-glucoside (1), hyperoside (2), hydrangenol-8-O-glucoside (3), swertisin (4), 7-methylisoorientin (5), 4,5-O-dicaffeoyl-quinic acid (6), 3,5-di-O-caffeoyl-quinic acid (7), and chlorogenic acid (8) have been isolated as major phenolic compounds of the tested extracts and, together with eight terpenoids (9-16) previously obtained from different Scorzonera species, have been tested for the inhibition of TNF-α production, unfortunately with no activity comparable with standard.

Department of Molecular Biology and Pharmaceutical Biotechnology Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences Brno Palackého tř 1946 1 61242 Brno Czech Republic

Department of Natural Drugs Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences Brno Palackého tř 1946 1 61242 Brno Czech Republic

Department of Pharmacognosy and Botany The University of Veterinary Medicine and Pharmacy in Košice Komenského 73 041 81 Košice Slovakia

Department of Pharmacognosy Faculty of Pharmacy Ankara University 06100 Ankara Turkey

Mass Spectrometry Group Institute of Organic Chemistry and Biochemistry v v i Academy of Sciences of the Czech Republic Flemingovo nám 2 166 10 Prague 6 Czech Republic

NMR Laboratory Institute of Organic Chemistry and Biochemistry v v i Academy of Sciences of the Czech Republic Flemingovo nám 2 166 10 Prague 6 Czech Republic

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Atanasov A.G., Waltenberger B., Pferschy-Wenzig E.M., Linder T., Wawrosch C., Uhrin P., Temml V., Wang L., Schwaiger S., Heiss E.H., et al. Discovery and resupply of pharmacologically active plant-derived natural products: A review. Biotechnol. Adv. 2015 doi: 10.1016/j.biotechadv.2015.08.001. PubMed DOI PMC

Yesilada E. Evaluation of the anti-inflammatory activity of the Turkish medicinal plant Sambucus ebulus. Chem. Nat. Prod. 1997;33:539–540.

Bandgar B.P., Patil S.A., Totre J.V., Korbad B.L., Gacche R.N., Hote B.S., Jalde S.S., Chavan H.V. Synthesis and biological evaluation of nitrogen-containing benzophenone analogues as TNF-a and IL-6 inhibitors with antioxidant activity. Bioorg. Med. Chem. Lett. 2010;20:2292–2296. doi: 10.1016/j.bmcl.2010.02.001. PubMed DOI

Leiro J.M., Varela M., Piazzon M.C., Arranz J.A., Noya M., Lamas J. The anti-inflammatory activity of the polyphenol resveratrol may be partially related to inhibition of tumour necrosis factor-α (TNF-α) pre-mRNA splicing. Mol. Immunol. 2010;47:1114–1120. doi: 10.1016/j.molimm.2009.10.030. PubMed DOI

Chauhan P.S., Satti N.K., Sharma V.K., Dutt P., Suri K.A., Bani S. Amelioration of inflammatory responses by chlorogenic acid via suppression of pro-inflammatory mediators. J. Appl. Pharm. Sci. 2011;1:67–75.

Benbarek H., Deby-Dupont G., Deby C., Serteyn D. Direct stimulation of the oxidative activity of isolated equine neutrophils by TNF-α and IL-1β. Vet. Immunol. Immunopathol. 2008;121:101–106. doi: 10.1016/j.vetimm.2007.09.006. PubMed DOI

Rao P.P.N., Kabir S.N., Mohamed T. Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Progress in Small Molecule Drug Development. Pharmaceuticals. 2010;3:1530–1549. doi: 10.3390/ph3051530. PubMed DOI PMC

Zelova H., Hosek J. TNF-α signalling and inflammation: Interactions between old acquaintances. Inflamm. Res. 2013;62:641–651. doi: 10.1007/s00011-013-0633-0. PubMed DOI

Cheng J., Chen M., Wallace D., Tith S., Arrhenius T., Kashiwagi H., Ono Y., Ishikawa A., Sato H., Kozono T., et al. Discovery and structure-activity relationship of coumarin derivatives as TNF-α inhibitors. Bioorg. Med. Chem. Lett. 2004;14:2411–2415. PubMed

Folmer F., Jaspars M., Solano G., Cristofanon S., Henry E., Tabudravu J., Black K., Green D.H., Küpper F.C., Aalbersberg W., et al. The inhibition of TNF-α-induced NF-κB activation by marine natural products. Biochem. Pharmacol. 2009;78:592–606. doi: 10.1016/j.bcp.2009.05.009. PubMed DOI

Nam N.H., Jae Y.Y. NF-κB Inhibitory Activities of the Methanol Extracts and some Constituents therein of some Vietnamese Medicinal Plants. Sci. Pharm. 2009;77:389–399. doi: 10.3797/scipharm.0903-15. DOI

Zidorn C., Ellmerer E.P., Sturm S., Stuppner H. Tyrolobibenzyls E and F from Scorzonera humilis and distribution of caffeic acid derivatives, lignans and tyrolobibenzyls in European taxa of the subtribe Scorzonerinae (Lactuceae, Asteraceae) Phytochemistry. 2003;63:61–67. doi: 10.1016/S0031-9422(02)00714-8. PubMed DOI

Tsevegsuren N., Edrada R.A., Lin W., Ebel R., Torre C., Ortlepp S., Wray V., Proksch P. Biologically Active Natural Products from Mongolian Medicinal Plants Scorzonera divaricata and Scorzonera pseudodivaricata. J. Nat. Prod. 2007;70:962–967. doi: 10.1021/np070013r. PubMed DOI

Wang Y., Edrada-Ebel R.A., Tsevegsuren N., Sendker J., Braun M., Wray V., Lin W., Proksch P. Dihydrostilbene derivatives from the Mongolian medicinal plant Scorzonera radiata. J. Nat. Prod. 2009;72:671–675. doi: 10.1021/np800782f. PubMed DOI

Zidorn C., Ellmerer-Müller E.P., Stuppner H. Sesquiterpenoids from Scorzonera hispanica L. Pharmazie. 2000;55:550–551. PubMed

Auzi A.R., Hawisa N.T., Sherif F.M., Sarker S.D. Neuropharmacological properties of Launaea resedifolia. Rev. Bras. Farmacogn. 2007;17:160–165. doi: 10.1590/S0102-695X2007000200004. DOI

Zhu Y., Wu Q., Hu P., Wu W. Biguaiascorzolides A and B: Two novel dimeric guaianolides with a rare skeleton, from Scorzonera austriaca. Food Chem. 2009;114:1316–1320. doi: 10.1016/j.foodchem.2008.11.009. DOI

Sezik E., Yeşilada E., Tabata M., Honda G., Takaishi Y., Fujita T., Tanaka T., Takeda Y. Traditional medicine in Turkey VIII. Folk medicine in East Anatolia; Erzurum, Erzincan, Ağrı, Kars, Iğdır Provinces. Econ. Bot. 1997;51:195–211. doi: 10.1007/BF02862090. DOI

Baytop T. Türkiye’de Bitkiler ile Tedavi (Theraphy with Medicinal Plants in Turkey) Nobel publishers; Istanbul, Turkey: 1999.

Donia A.M. Phytochemical and pharmacological studies on Scorzonera alexandrina Bioss. J. Saudi Chem. Soc. 2013 doi: 10.1016/j.jscs.2013.01.001. in press. DOI

Bahadir Ö., Saltan Çitoğlu G., Šmejkal K., Dall'Acqua S., Özbek H., Cvačka J., Žemlička M. Analgesic Compounds from Scorzonera latifolia (Fisch. and Mey.) DC. J. Ethnopharmacol. 2010;131:83–87. doi: 10.1016/j.jep.2010.06.003. PubMed DOI

Küpeli Akkol E., Acıkara Bahadır Ö., Süntar İ., Çitoğlu Saltan G., Keleş H., Ergene B. Enhancement of wound healing by topical application of Scorzonera species: Determination of the constituents by HPLC with new validated reverse phase method. J. Ethnopharmacol. 2011;137:1018–1027. doi: 10.1016/j.jep.2011.07.029. PubMed DOI

Küpeli Akkol E., Acıkara Bahadır Ö., Süntar İ., Ergene B., Çitoğlu Saltan G. Ethnopharmacological evaluation of some Scorzonera species: In vivo anti-inflammatory and antinociceptive effects. J. Ethnopharmacol. 2012;140:261–270. doi: 10.1016/j.jep.2012.01.015. PubMed DOI

Süntar İ., Acıkara Bahadır Ö., Çitoğlu Saltan G., Keleş H., Ergene B., Küpeli Akkol E. In vivo and In vitro Evaluation of the Therapeutic Potential of Some Scorzonera Species as Wound healing Agent. Curr. Pharm. Des. 2011;137:1018–1027. PubMed

Amdekar S., Roy P., Singh V., Kumar A., Singh R., Sharma P. Anti-Inflammatory Activity of Lactobacillus on Carrageenan-Induced Paw Edema in Male Wistar Rats. Int. J. Inflamm. 2012;2012 doi: 10.1155/2012/752015. PubMed DOI PMC

Kim K.R., Jeong C.K., Park K.K., Choi J.H., Park J.H.Y., Lim S.S., Chung W.Y. Anti-Inflammatory Effects of Licorice and Roasted Licorice Extracts on TPA-Induced Acute Inflammation and Collagen-Induced Arthritis in Mice. J. Biomed. Biotechnol. 2010;2010 doi: 10.1155/2010/709378. PubMed DOI PMC

Yeşilada E., Üstün O., Sezik E., Takaishi Y., Ono Y., Honda G. Inhibitory effects of Turkish folk remedies on inflammatory cytokines: Interleukin-1α, interleukin-1β and tumor necrosis factor α. J. Ethnopharmacol. 1997;58:59–73. doi: 10.1016/S0378-8741(97)00076-7. PubMed DOI

Schwaiger S., Zeller I., Pölzelbauer P., Frotschnig S., Laufer G., Messner B., Pieri V., Stuppner H., Bernhard D. Identification and pharmacological characterization of the anti-inflammatory principal of the leaves of dwarf elder (Sambucus ebulus L.) J. Ethnopharmacol. 2011;133:704–709. doi: 10.1016/j.jep.2010.10.049. PubMed DOI PMC

Kaileh M., Berghe W.V., Boone E., Essawi T., Haegeman G. Screening of indigenous Palestinian medicinal plants for potential anti-inflammatory and cytotoxic activity. J. Ethnopharmacol. 2007;113:510–516. doi: 10.1016/j.jep.2007.07.008. PubMed DOI

Siriwatanametanon N., Fiebich B.L., Efferth T., Prieto J.M., Heinrich M. Traditionally used Thai medicinal plants: In vitro anti-inflammatory, anticancer and antioxidant activities. J. Ethnopharmacol. 2010;130:196–207. doi: 10.1016/j.jep.2010.04.036. PubMed DOI

Borchers A.T., Keen C.L., Stern J.S., Gershwin M.E. Inflammation and Native American medicine: The role of botanicals. Am J Clin Nutr. 2000;72:339–347. PubMed

Dos Santos M.D., Almeida M.C., Lopes N.P., Souza G.E.P. Evaluation of the anti-inflammatory, analgesic and antipyretic activities of natural polyphenol chlorogenic acid. Biol. Pharm. Bull. 2006;29:2236–2240. doi: 10.1248/bpb.29.2236. PubMed DOI

Yonathan M., Asres K., Assefa A., Bucar F. In vivo anti-inflammatory and antinociceptive activities of Cheilanthes farinose. J. Ethnopharmacol. 2006;108:462–470. doi: 10.1016/j.jep.2006.06.006. PubMed DOI

Hošek J., Šmejkal K. Flavonoids as Anti-inflammatory Agents. In: Parnham M., editor. Encyclopedia of Inflammatory Diseases. Springer; New York, NY, USA: (Online)

Comalada M., Ballester I., Bailon E., Sierra S., Xaus J., Galvez J., Sanchez de Medina F., Zarzuelo A. Inhibition of pro-inflammatory markers in primary bone marrow-derived mouse macrophages by naturally occurring flavonoids: Analysis of the structure-activity relationship. Biochem. Pharmacol. 2006;72:1010–1021. doi: 10.1016/j.bcp.2006.07.016. PubMed DOI

Paul A.T., Gohil V.M., Bhutani K.K. Modulating TNF-α signaling with natural products. Drug Discov. Today. 2006;11:725–732. doi: 10.1016/j.drudis.2006.06.002. PubMed DOI

Yamamoto Y., Gaynor R.B. Therapeutic potential of inhibition of the NF-κB pathway in the treatment of inflammation and cancer. J. Clin. Investig. 2001;107:135–142. doi: 10.1172/JCI11914. PubMed DOI PMC

Jeong G.-S., Bae J.-S. Anti-Inflammatory Effects of Triterpenoids; Naturally Occurring and Synthetic Agents. Mini-Rev. Org. Chem. 2014;11:316–329. doi: 10.2174/1570193X1103140915111703. DOI

Sultana N., Saify Z.S. Naturally occurring and synthetic agents as potential anti-inflammatory and immunomodulants. Anti-Inflamm. Anti-Allergy Agents Med. Chem. 2012;11:3–19. doi: 10.2174/187152312803476264. PubMed DOI

Shen W., Qi R., Zhang J., Wang Z., Wang H., Hu C., Zhao Y., Bie M., Wang Y., Fu Y., Chen M., Lu D. Chlorogenic acid inhibits LPS-induced microglial activation and improves survival of dopaminergic neurons. Brain Res. Bull. 2012;88:487–494. doi: 10.1016/j.brainresbull.2012.04.010. PubMed DOI

Ku S.K., Zhou W., Lee W., Han M.S., Na M., Bae J.S. Anti-inflammatory effects of hyperoside in human endothelial cells and in mice. Inflammation. 2015;38:784–799. doi: 10.1007/s10753-014-9989-8. PubMed DOI

Srivastava P., Mohanti S., Bawankule D.U., Khan F., Shanker K. Effect of Pluchea lanceolata bioactives in LPS-induced neuroinflammation in C6 rat glial cells. Naunyn-Schmiedeberg’s Arch. Pharmacol. 2014;387:119–127. doi: 10.1007/s00210-013-0924-6. PubMed DOI

Chen J.-J., Tsai Y.-C., Hwang T.-L., Wang T.-C. Thymol, Benzofuranoid, and Phenylpropanoid Derivatives: Anti-inflammatory Constituents from Eupatorium cannabinum. J. Nat. Prod. 2011;74:1021–1027. PubMed

Hashimoto T., Tori M., Asakawa Y. Three dihydroisocoumarine glucosides from Hydrangea macrophylla subsp. Serrate. Phytochemistry. 1987;26:3323–3330. doi: 10.1016/S0031-9422(00)82497-8. DOI

Frank J.H., Powder-George Y.M., Ramsewak R.S., Reynolds W.F. Variable-Temperature 1H-NMR Studies on Two C-Glycosylflavones. Molecules. 2012;17:7914–7926. doi: 10.3390/molecules17077914. PubMed DOI PMC

Pukalskas A., Venskutonis P.R., Dijkgraaf I., van Beek T.A. Isolation, identification and activity of natural antioxidants from costmary (Chrysanthemum balsamita) cultivated in Lithuania. Food Chem. 2010;122:804–811. doi: 10.1016/j.foodchem.2010.03.064. DOI

Acikara Bahadir Ö., Saltan Citoglu G., Dall'Acqua S., Özbek H., Cvačka J., Žemlička M., Šmejkal K. Bioassay-guided isolation of the antinociceptive compounds motiol and β-sitosterol from Scorzonera latifolia root extract. Pharmazie. 2014;69:711–714. PubMed

Paraschos S., Magiatis P., Kalpoutzakis E., Harvala C., Skaltsounis A.-L. Three New Dihydroisocoumarins from the Greek Endemic Species Scorzonera cretica. J. Nat. Prod. 2001;64:1585–1587. doi: 10.1021/np0103665. PubMed DOI

Acikara Bahadir Ö., Saltan Citoglu G., Dall’Acqua S., Šmejkal K., Cvačka J., Žemlička M. A new triterpene from Scorzonera latifolia (Fisch. and Mey.) DC. Nat. Prod. Res. 2012;26:1892–1897. doi: 10.1080/14786419.2011.625644. PubMed DOI