Biosynthesis and bioactivity of Cynara cardunculus L. guaianolides and hydroxycinnamic acids: a genomic, biochemical and health-promoting perspective

  • Patrícia A. B. Ramos
  • Ana M. Ferro
  • M. Margarida Oliveira
  • Sónia Gonçalves
  • Carmen S. R. Freire
  • Armando J. D. Silvestre
  • Maria F. DuarteEmail author


Cynara cardunculus health benefits have aroused much interest, leading to the discovery of valuable bioactive compounds with a crucial role in plant defence. Guaianolides and hydroxycinnamic acids, mainly represented by cynaropicrin and chlorogenic acid, constitute the major secondary metabolites in leaves (9.5% and 10.4% dry weight, respectively). These compounds evidence biological activity, namely antioxidant, antitumoral, hepatoprotective, antimicrobial and anti-hyperlipidemic effects. Therefore, numerous efforts have been undertaken in this species to unveil the biosynthetic pathways of such compounds, by means of genomic and biochemical approaches, which could support advances, via breeding programs, in C. cardunculus chemical composition and, consequently, in the improvement of its extracts biological activity. Addressing this challenge, relevant genes in cynaropicrin biosynthesis, as well as in chlorogenic acid biosynthesis have been widely studied. The present review highlights the current knowledge on the biosynthesis and distribution of guaianolides and hydroxycinnamic acids, especially of cynaropicrin and chlorogenic acid in C. cardunculus, as well as their association with plant defence mechanisms and human health-promoting effects, prospecting the valorisation of this Mediterranean species as a potential source of bioactive compounds for food, nutraceutical and pharmaceutical purposes.


Biological activity Chlorogenic acid Cynara cardunculus L. Cynaropicrin Genotype–phenotype association 



Alanine transaminase


Aspartic transaminase


Adenosine triphosphate


4-Coumarate:coenzyme A ligase


p-Coumaroyl ester 3′-hydroxylase


Cinnamate 4-hydroxylase


Chlorogenic acid equivalents


Costunolide synthase




Dry weight


Farnesyl diphosphate


Ferric reducing antioxidant power


Germacrene A oxidase


Germacrene A synthase


Geranyl diphosphate


Hydrogen atom transfer


Human hepatocellular carcinoma


Hydroxycinnamoyl-CoA:shikimate/quinate hydroxycinnamoyl transferase


Hydroxycinnamoyl-CoA:quinate hydroxycinnamoyl transferase


Isopentenyl diphosphate


Minimum bactericidal concentration


Minimum fungicidal concentration


Minimum inhibitory concentration


Methicillin-resistant Staphylococcus aureus


Nicotinamide adenine dinucleotide phosphate, reduced form


Phenylalanine ammonia-lyase


Single electron transfer


Single nucleotide polymorphism


Triple-negative breast cancer


Ultraviolet radiation



This work was supported by the Program Alentejo 2020, through the European Fund for Regional Development (FEDER) under the scope of ValBioTecCynara—Economic Valorisation of Cardoon (Cynara cardunculus): Study of natural variability and biotechnological applications (ALT20-03-0145-FEDER-000038). This work was also funded through FCT under the Project UID/AGR/00115/2019 to ICAAM. The authors also want to acknowledge Project CICECO-Aveiro Institute of Materials, POCI-01-0145-FEDER-007679 (FCT Reference: UID/CTM/50011/2019), financed by National Funds through the FCT/MCTES and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. FCT is also acknowledged for the research contract under “Investigador FCT” to C. S. R. Freire (IF/01407/2012), and for funding the MultiBiorefinery Project (POCI-01-0145-FEDER-016403) which funded the PostDoctoral Grant of P. A. B. Ramos.


  1. Adzet T, Puigmacia M (1985) High performance liquid chromatography of caffeoylquinic acid derivatives of Cynara scolymus L. leaves. J Chromatogr A 348:447–453. CrossRefGoogle Scholar
  2. Adzet T, Camarasa J, Laguna JC (1987) Hepatoprotective activity of polyphenolic compounds from Cynara scolymus against CCl4 toxicity in isolated rat hepatocytes. J Nat Prod 50:612–617. CrossRefPubMedGoogle Scholar
  3. Ahn J, Gammon MD, Santella RM et al (2005) Associations between breast cancer risk and the catalase genotype, fruit and vegetable consumption, and supplement use. Am J Epidemiol 162:943–952. CrossRefPubMedGoogle Scholar
  4. Alfaro S, Mutis A, Palma R et al (2013) Influence of genotype and harvest year on polyphenol content and antioxidant activity in murtilla (Ugni molinae Turcz) fruit. J Soil Sci Plant Nutr 13:67–78. CrossRefGoogle Scholar
  5. Bachelier A, Mayer R, Klein CD (2006) Sesquiterpene lactones are potent and irreversible inhibitors of the antibacterial target enzyme MurA. Bioorg Med Chem Lett 16:5605–5609. CrossRefPubMedGoogle Scholar
  6. Bandonienė D, Venskutonis PR, Gruzdienė D, Murkovic M (2002) Antioxidative activity of sage (Salvia officinalis L.), savory (Satureja hortensis L.) and borage (Borago officinalis L.) extracts in rapeseed oil. Eur J Lipid Sci Technol 104:286–292.;2-O CrossRefGoogle Scholar
  7. Barbetti P, Chiappini I, Fardella G, Grandolini G (1993) Grosulfeimin and new related guaianolides from Cynara scolymus L. Nat Prod Lett 3:21–30. CrossRefGoogle Scholar
  8. Baumann TW, Röhrig L (1989) Formation and intracellular accumulation of caffeine and chlorogenic acid in suspension cultures of Coffea arabica. Phytochemistry 28:2667–2669. CrossRefGoogle Scholar
  9. Becerra-Moreno A, Benavides J, Cisneros-Zevallos L, Jacobo-Velázquez DA (2012) Plants as biofactories: glyphosate-induced production of shikimic acid and phenolic antioxidants in wounded carrot tissue. J Agric Food Chem 60:11378–11386. CrossRefPubMedGoogle Scholar
  10. Beckman CH (2000) Phenolic-storing cells: keys to programmed cell death and periderm formation in wilt disease resistance and in general defence responses in plants? Physiol Mol Plant Pathol 57:101–110. CrossRefGoogle Scholar
  11. Bennett MH, Mansfield JW, Lewis MJ, Beale MH (2002) Cloning and expression of sesquiterpene synthase genes from lettuce (Lactuca sativa L.). Phytochemistry 60:255–261. CrossRefPubMedGoogle Scholar
  12. Bouwmeester HJ, Kodde J, Verstappen FW et al (2002) Isolation and characterization of two germacrene A synthase cDNA clones from chicory. Plant Physiol 129:134–144. CrossRefPubMedPubMedCentralGoogle Scholar
  13. Brand-Williams W, Cuvelier ME, Berset C (1995) Use of a free radical method to evaluate antioxidant activity. LWT Food Sci Technol 28:25–30. CrossRefGoogle Scholar
  14. Brás T, Guerreiro O, Duarte MF, Neves LA (2015) Impact of extraction parameters and concentration by nanofiltration on the recovery of phenolic compounds from Cynara cardunculus var. altilis: assessment of antioxidant activity. Ind Crops Prod 67:137–142. CrossRefGoogle Scholar
  15. Brown JE, Rice-Evans CA (1998) Luteolin-rich artichoke extract protects low density lipoprotein from oxidation in vitro. Free Radic Res 29:247–255. CrossRefPubMedGoogle Scholar
  16. Cantos E, Espín JC, Tomás-Barberán FA (2001) Effect of wounding on phenolic enzymes in six minimally processed lettuce cultivars upon storage. J Agric Food Chem 49:322–330. CrossRefPubMedGoogle Scholar
  17. Chen JH, Ho CT (1997) Antioxidant activities of caffeic acid and its related hydroxycinnamic acid compounds. J Agric Food Chem 45:2374–2378. CrossRefGoogle Scholar
  18. Cho JY, Baik KU, Jung JH, Park MH (2000) In vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa. Eur J Pharmacol 398:399–407. CrossRefPubMedGoogle Scholar
  19. Cho JY, Kim AR, Jung JH et al (2004) Cytotoxic and pro-apoptotic activities of cynaropicrin, a sesquiterpene lactone, on the viability of leukocyte cancer cell lines. Eur J Pharmacol 492:85–94. CrossRefPubMedGoogle Scholar
  20. Clé C, Hill LM, Niggeweg R et al (2008) Modulation of chlorogenic acid biosynthesis in Solanum lycopersicum; consequences for phenolic accumulation and UV-tolerance. Phytochemistry 69:2149–2156. CrossRefPubMedGoogle Scholar
  21. Coinu R, Carta S, Urgeghe PP et al (2007) Dose-effect study on the antioxidant properties of leaves and outer bracts of extracts obtained from Violetto di Toscana artichoke. Food Chem 101:524–531. CrossRefGoogle Scholar
  22. Comino C, Lanteri S, Portis E et al (2007) Isolation and functional characterization of a cDNA coding a hydroxycinnamoyltransferase involved in phenylpropanoid biosynthesis in Cynara cardunculus L. BMC Plant Biol 7:14. CrossRefPubMedPubMedCentralGoogle Scholar
  23. Comino C, Hehn A, Moglia A et al (2009) The isolation and mapping of a novel hydroxycinnamoyltransferase in the globe artichoke chlorogenic acid pathway. BMC Plant Biol 9:30. CrossRefPubMedPubMedCentralGoogle Scholar
  24. Cooper GM, Hausman RE (2004) Cancer. In: Cooper GM (ed) The cell: a molecular approach, 3rd edn. The American Society for Microbiology, Washington, pp 631–673Google Scholar
  25. Cravotto G, Nano GM, Binello A et al (2005) Chemical and biological modification of cynaropicrin and grosheimin: a structure–bitterness relationship study. J Sci Food Agric 85:1757–1764. CrossRefGoogle Scholar
  26. Cuenca-Estrella M, Gomez-Lopez A, Buitrago MJ et al (2006) In vitro activities of 10 combinations of antifungal agents against the multiresistant pathogen Scopulariopsis brevicaulis. Antimicrob Agents Chemother 50:2248–2250. CrossRefPubMedPubMedCentralGoogle Scholar
  27. Cuvelier M-E, Richard H, Berset C (1992) Comparison of the antioxidative activity of some acid-phenols: structure–activity relationship. Biosci Biotechnol Biochem 56:324–325. CrossRefGoogle Scholar
  28. de Kraker J-W, Franssen MCR, Joerink M et al (2002) Biosynthesis of costunolide, dihydrocostunolide, and leucodin. Demonstration of cytochrome P450-catalyzed formation of the lactone ring present in sesquiterpene lactones of chicory. Plant Physiol 129:257–268. CrossRefPubMedPubMedCentralGoogle Scholar
  29. De Paolis A, Pignone D, Morgese A, Sonnante G (2008) Characterization and differential expression analysis of artichoke phenylalanine ammonia-lyase-coding sequences. Physiol Plant 132:33–43. CrossRefPubMedGoogle Scholar
  30. Deidda M (1967) Contributo al miglioramento genetico del carciofo. In: Atti 1o Congr. Int. di Studi sul Carciofo. Minerva Medica, Torino, pp 157–174Google Scholar
  31. Dewick PM (2002) The mevalonate and deoxyxylulose phosphate pathways: terpenoids and steroids. In: Dewick PM (ed) Medicinal natural products—a biosynthetic approach, 2nd edn. Wiley, Chichester, pp 167–289Google Scholar
  32. Dixon RA, Paiva NL (1995) Stress-induced phenylpropanoid metabolism. Plant Cell 7:1085–1097. CrossRefPubMedPubMedCentralGoogle Scholar
  33. Duarte P, Figueiredo R, Pereira S, Pissara J (2006) Structural characterization of the stigma-style complex of Cynara cardunculus (Asteraceae) and immunolocalization of cardosins A and B during floral development. Can J Bot 84:737–749. CrossRefGoogle Scholar
  34. Eljounaidi K, Cankar K, Comino C et al (2014) Cytochrome P450s from Cynara cardunculus L. CYP71AV9 and CYP71BL5, catalyze distinct hydroxylations in the sesquiterpene lactone biosynthetic pathway. Plant Sci 223:59–68. CrossRefPubMedGoogle Scholar
  35. Eljounaidi K, Comino C, Moglia A et al (2015) Accumulation of cynaropicrin in globe artichoke and localization of enzymes involved in its biosynthesis. Plant Sci 239:128–136. CrossRefPubMedGoogle Scholar
  36. European Centre for Disease Prevention and Control (2018) Surveillance of antimicrobial resistance in Europe—Annual Report of the European Antimicrobial Resistance Surveillance Network (EARS-Net) 2017. ECDC, Stockholm. Cited 24 January 2019
  37. Falleh H, Ksouri R, Chaieb K et al (2008) Phenolic composition of Cynara cardunculus L. organs, and their biological activities. C R Biol 331:372–379. CrossRefPubMedGoogle Scholar
  38. Farag MA, El-Ahmady SH, Elian FS, Wessjohann LA (2013) Metabolomics driven analysis of artichoke leaf and its commercial products via UHPLC-q-TOF-MS and chemometrics. Phytochemistry 95:177–187. CrossRefPubMedGoogle Scholar
  39. Faulds CB, Williamson G (1999) The role of hydroxycinnamates in the plant cell wall. J Sci Food Agric 79:393–395.;2-H CrossRefGoogle Scholar
  40. Fernandes MB, Scotti MT, Ferreira MJP, Emerenciano VP (2008) Use of self-organizing maps and molecular descriptors to predict the cytotoxic activity of sesquiterpene lactones. Eur J Med Chem 43:2197–2205. CrossRefPubMedGoogle Scholar
  41. Fernández J, Curt MD, Aguado PL (2006) Industrial applications of Cynara cardunculus L. for energy and other uses. Ind Crops Prod 24:222–229. CrossRefGoogle Scholar
  42. Ferro A (2016) A reverse genetics approach to identify Cynara cardunculus L. genotypes with improved bioactive content. PhD dissertation in Biochemistry, speciality Molecular Biology. Institute for Chemical and Biological Technology (ITQB), New University of Lisbon (UNL), PortugalGoogle Scholar
  43. Ferro AM, Ramos P, Guerreiro O et al (2017) Impact of novel SNPs identified in Cynara cardunculus genes on functionality of proteins regulating phenylpropanoid pathway and their association with biological activities. BMC Genom 18:183. CrossRefGoogle Scholar
  44. Ferro AM, Ramos P, Guerra  et al (2018) Haplotype analysis of the germacrene A synthase gene and association with cynaropicrin content and biological activities in Cynara cardunculus. Mol Genet Genomics 293:417–433. CrossRefPubMedGoogle Scholar
  45. Food and Agriculture Organization of the United States (2017) Crop Statistics. Cited 24 January 2019
  46. Foury C (1969) Étude de la biologie florale de l’artichaut (Cynara scolymus L.). Application a la sélection 2eme partie. Étude des descendances obtenues en fécondation contrôlée. Ann Amélior Plantes 19:23–52Google Scholar
  47. Fratianni F, Tucci M, De Palma M et al (2007) Polyphenolic composition in different parts of some cultivars of globe artichoke (Cynara cardunculus L. var. scolymus (L.) Fiori). Food Chem 104:1282–1286. CrossRefGoogle Scholar
  48. Fritsche J, Beindorff C, Dachtler M et al (2002) Isolation, characterization and determination of minor artichoke (Cynara scolymus L.) leaf extract compounds. Eur Food Res Technol 215:149–157. CrossRefGoogle Scholar
  49. Gebhardt R (1997) Antioxidative and protective properties of extracts from leaves of the artichoke (Cynara scolymus L.) against hydroperoxide-induced oxidative stress in cultured rat hepatocytes. Toxicol Appl Pharmacol 144:279–286. CrossRefPubMedGoogle Scholar
  50. Gebhardt R (2005) Choleretic and anticholestatic activities of flavonoids of artichoke (Cynara cardunculus L. subsp. scolymus L. Hayek). Acta Hortic 681:429–436. CrossRefGoogle Scholar
  51. Ghantous A, Gali-Muhtasib H, Vuorela H et al (2010) What made sesquiterpene lactones reach cancer clinical trials? Drug Discov Today 15:668–678. CrossRefPubMedGoogle Scholar
  52. Ghrabi Z (2005) Cynara cardunculus L. var. sylvestris (Lamk.) Fiori. In: IUCN—International Union for Conservation of Nature and Natural Resources (ed) A guide to medicinal plants in North Africa. IUCN, Gland, pp 111–112Google Scholar
  53. Gominho J, Fernandez J, Pereira H (2001) Cynara cardunculus L.—a new fibre crop for pulp and paper production. Ind Crops Prod 13:1–10. CrossRefGoogle Scholar
  54. Gominho J, Lourenço A, Palma P et al (2011) Large scale cultivation of Cynara cardunculus L. for biomass production—a case study. Ind Crops Prod 33:1–6. CrossRefGoogle Scholar
  55. Göpfert JC, MacNevin G, Ro D-K, Spring O (2009) Identification, functional characterization and developmental regulation of sesquiterpene synthases from sunflower capitate glandular trichomes. BMC Plant Biol 9:86. CrossRefPubMedPubMedCentralGoogle Scholar
  56. Gouveia SC, Castilho PC (2012) Phenolic composition and antioxidant capacity of cultivated artichoke, Madeira cardoon and artichoke-based dietary supplements. Food Res Int 48:712–724. CrossRefGoogle Scholar
  57. Gramazio P, Prohens J, Plazas M et al (2014) Location of chlorogenic acid biosynthesis pathway and polyphenol oxidase genes in a new interspecific anchored linkage map of eggplant. BMC Plant Biol 14:350. CrossRefPubMedPubMedCentralGoogle Scholar
  58. Guiné RPF, Tenreiro MIC, Correia AC et al (2016) Analysis of factors influencing the physical, chemical and sensorial properties of Serra da Estrela cheeses. J Food Meas Charact 10:643–657. CrossRefGoogle Scholar
  59. Gülçin I (2015) Fe3+–Fe2+ transformation method: an important antioxidant assay. In: Armstrong D (ed) Advanced protocols in oxidative stress III. Springer, New York, pp 233–246Google Scholar
  60. Gündüz K, Özdemir E (2014) The effects of genotype and growing conditions on antioxidant capacity, phenolic compounds, organic acid and individual sugars of strawberry. Food Chem 155:298–303. CrossRefPubMedGoogle Scholar
  61. Guo J, Carrington Y, Alber A, Ehlting J (2014) Molecular characterization of quinate and shikimate metabolism in Populus trichocarpa. J Biol Chem 289:23846–23858. CrossRefPubMedGoogle Scholar
  62. Halliwell B, Aeschbach R, Loliger J, Aruoma OI (1995) The characterization of antioxidants. Food Chem Toxicol 33:601–617CrossRefPubMedGoogle Scholar
  63. Henderson LM, Chappell JB (1996) NADPH oxidase of neutrophils. Biochim Biophys Acta Bioenerg 1273:87–107. CrossRefGoogle Scholar
  64. Hoffmann L, Maury S, Martz F et al (2003) Purification, cloning, and properties of an acyltransferase controlling shikimate and quinate ester intermediates in phenylpropanoid metabolism. J Biol Chem 278:95–103. CrossRefPubMedGoogle Scholar
  65. Hoffmann L, Besseau S, Geoffroy P et al (2004) Silencing of hydroxycinnamoyl-coenzyme A shikimate/quinate hydroxycinnamoyltransferase affects phenylpropanoid biosynthesis. Plant Cell 16:1446–1465. CrossRefPubMedPubMedCentralGoogle Scholar
  66. Hofinger BJ, Jing H-C, Hammond-Kosack KE, Kanyuka K (2009) High-resolution melting analysis of cDNA-derived PCR amplicons for rapid and cost-effective identification of novel alleles in barley. Theor Appl Genet 119:851–865. CrossRefPubMedGoogle Scholar
  67. Humphrey AJ, Beale MH (2006) Terpenes. In: Crozier A, Clifford MN, Ashihara H (eds) Plant secondary metabolites: occurrence, structure and role in the human diet, 1st edn. Blackwell Publishing Ltd., Oxford, pp 47–101CrossRefGoogle Scholar
  68. Ierna A, Mauromicale G (2010) Cynara cardunculus L. genotypes as a crop for energy purposes in a Mediterranean environment. Biomass Bioenergy 34:754–760. CrossRefGoogle Scholar
  69. Ikezawa N, Göpfert JC, Nguyen DT et al (2011) Lettuce costunolide synthase (CYP71BL2) and its homolog (CYP71BL1) from sunflower catalyze distinct regio- and stereoselective hydroxylations in sesquiterpene lactone metabolism. J Biol Chem 286:21601–21611. CrossRefPubMedPubMedCentralGoogle Scholar
  70. Kang K, Lee HJ, Kim CY et al (2007) The chemopreventive effects of Saussurea salicifolia through induction of apoptosis and phase II detoxification enzyme. Biol Pharm Bull 30:2352–2359. CrossRefPubMedGoogle Scholar
  71. Kirchhoff R, Beckers CH, Kirchhoff GM et al (1994) Increase in choleresis by means of artichoke extract. Phytomedicine 1:107–115. CrossRefPubMedGoogle Scholar
  72. Koehn FE, Carter GT (2005) The evolving role of natural products in drug discovery. Nat Rev Drug Discov 4:206–220. CrossRefPubMedGoogle Scholar
  73. Kraft K (1997) Artichoke leaf extract—recent findings reflecting effects on lipid metabolism, liver and gastrointestinal tracts. Phytomedicine 4:369–378. CrossRefPubMedGoogle Scholar
  74. Kukic J, Popovic V, Petrovic S et al (2008) Antioxidant and antimicrobial activity of Cynara cardunculus extracts. Food Chem 107:861–868. CrossRefGoogle Scholar
  75. Ky C-L, Louarn J, Dussert S et al (2001) Caffeine, trigonelline, chlorogenic acids and sucrose diversity in wild Coffea arabica L. and C. canephora P. accessions. Food Chem 75:223–230. CrossRefGoogle Scholar
  76. Lackner M, de Hoog GS, Verweij PE et al (2012) Species-specific antifungal susceptibility patterns of Scedosporium and Pseudallescheria species. Antimicrob Agents Chemother 56:2635–2642. CrossRefPubMedPubMedCentralGoogle Scholar
  77. Lallemand LA, Zubieta C, Lee SG et al (2012) A structural basis for the biosynthesis of the major chlorogenic acids found in coffee. Plant Physiol 160:249–260. CrossRefPubMedPubMedCentralGoogle Scholar
  78. Lanteri S, Saba E, Cadinu M et al (2004) Amplified fragment lenght polymorphism for genetic diversity assessment in globe artichoke. Theor Appl Genet 108:1534–1544. CrossRefPubMedGoogle Scholar
  79. Lattanzio V, Cardinali A, Di Venere D et al (1994) Browning phenomena in stored artichoke (Cynara scolymus L.) heads: enzymic or chemical reactions? Food Chem 50:1–7. CrossRefGoogle Scholar
  80. Lee KH, Huang ES, Piantadosi C et al (1971) Cytotoxicity of sesquiterpene lactones. Cancer Res 31:1649–1654PubMedGoogle Scholar
  81. Leiss KA, Maltese F, Choi YH et al (2009) Identification of chlorogenic acid as a resistance factor for thrips in Chrysanthemum. Plant Physiol 150:1567–1575. CrossRefPubMedPubMedCentralGoogle Scholar
  82. Lepelley M, Cheminade G, Tremillon N et al (2007) Chlorogenic acid synthesis in coffee: an analysis of CGA content and real-time RT-PCR expression of HCT, HQT, C3H1, and CCoAOMT1 genes during grain development in C. canephora. Plant Sci 172:978–996. CrossRefGoogle Scholar
  83. Li XL, Qian PL, Liu ZY et al (2005) Sesquiterpenoids from Cynara scolymus. Heterocycles 65:287–291CrossRefGoogle Scholar
  84. Liu R, Hsieh KL, Liu JK (2009) A new sesquiterpene lactone from the leaves of Cynara scolymus (Compositae). Acta Bot Yunnan 31:383–385. CrossRefGoogle Scholar
  85. Liu Q, Majdi M, Cankar K et al (2011) Reconstitution of the costunolide biosynthetic pathway in yeast and Nicotiana benthamiana. PLoS ONE 6:e23255. CrossRefPubMedPubMedCentralGoogle Scholar
  86. Lombardo S, Pandino G, Mauromicale G et al (2010) Influence of genotype, harvest time and plant part on polyphenolic composition of globe artichoke [Cynara cardunculus L. var. scolymus (L.) Fiori]. Food Chem 119:1175–1181. CrossRefGoogle Scholar
  87. Lombardo S, Pandino G, Ierna A, Mauromicale G (2012) Variation of polyphenols in a germplasm collection of globe artichoke. Food Res Int 46:544–551. CrossRefGoogle Scholar
  88. López Anido FS, Firpo IT, García SM, Cointry EL (1998) Estimation of genetic parameters for yield traits in globe artichoke (Cynara scolymus L.). Euphytica 103:61–66. CrossRefGoogle Scholar
  89. Lotfy S, Fleuriet A, Macheix J-J (1992) Partial purification and characterization of hydroxycinnamoyl CoA: transferases from apple and date fruits. Phytochemistry 31:767–772. CrossRefGoogle Scholar
  90. Louro Martins AP, Pestana de Vasconcelos MM, de Sousa RB (1996) Thistle (Cynara cardunculus L) flower as a coagulant agent for cheesemaking. Short characterization. Lait 76:473–477. CrossRefGoogle Scholar
  91. Maher EA, Bate NJ, Ni W et al (1994) Increased disease susceptibility of transgenic tobacco plants with suppressed levels of preformed phenylpropanoid products. Proc Natl Acad Sci 91:7802–7806. CrossRefPubMedGoogle Scholar
  92. Menin B, Comino C, Moglia A et al (2010) Identification and mapping of genes related to caffeoylquinic acid synthesis in Cynara cardunculus L. Plant Sci 179:338–347. CrossRefGoogle Scholar
  93. Menin B, Comino C, Portis E et al (2012) Genetic mapping and characterization of the globe artichoke (+)-germacrene A synthase gene, encoding the first dedicated enzyme for biosynthesis of the bitter sesquiterpene lactone cynaropicrin. Plant Sci 190:1–8. CrossRefPubMedGoogle Scholar
  94. Meriçli AH, Seyhan GV (1998) Constituents of the leaves of Cynara cardunculus L. naturalized around Sinop. Acta Pharm Turc 40:137–139Google Scholar
  95. Mhlongo MI, Piater LA, Steenkamp PA et al (2015) Metabolomic fingerprinting of primed tobacco cells provide the first evidence for the biological origin of cis-chlorogenic acid. Biotechnol Lett 37:205–209. CrossRefPubMedGoogle Scholar
  96. Miccadei S, Di Venere D, Cardinali A et al (2008) Antioxidative and apoptotic properties of polyphenolic extracts from edible part of artichoke (Cynara scolymus L.) on cultured rat hepatocytes and on human hepatoma cells. Nutr Cancer 60:276–283. CrossRefPubMedGoogle Scholar
  97. Mileo AM, Di Venere D, Linsalata V et al (2012) Artichoke polyphenols induce apoptosis and decrease the invasive potential of the human breast cancer cell line MDA-MB-231. J Cell Physiol 227:3301–3309. CrossRefPubMedGoogle Scholar
  98. Miller T (1975) New artichoke clones. N Z J Agric 131:33–35Google Scholar
  99. Moglia A, Lanteri S, Comino C et al (2008) Stress-induced biosynthesis of dicaffeoylquinic acids in globe artichoke. J Agric Food Chem 56:8641–8649. CrossRefPubMedGoogle Scholar
  100. Moglia A, Comino C, Portis E et al (2009) Isolation and mapping of a C3′H gene (CYP98A49) from globe artichoke, and its expression upon UV-C stress. Plant Cell Rep 28:963–974. CrossRefPubMedGoogle Scholar
  101. Moglia A, Lanteri S, Comino C et al (2014) Dual catalytic activity of hydroxycinnamoyl-coenzyme A quinate transferase from tomato allows it to moonlight in the synthesis of both mono- and dicaffeoylquinic acids. Plant Physiol 166:1777–1787. CrossRefPubMedPubMedCentralGoogle Scholar
  102. Moglia A, Acquadro A, Eljounaidi K et al (2016) Genome-wide identification of BAHD acyltransferases and in vivo characterization of HQT-like enzymes involved in caffeoylquinic acid synthesis in globe artichoke. Front Plant Sci 7:1424. CrossRefPubMedPubMedCentralGoogle Scholar
  103. Mondolot L, La Fisca P, Buatois B et al (2006) Evolution in caffeoylquinic acid content and histolocalization during Coffea canephora leaf development. Ann Bot 98:33–40. CrossRefPubMedPubMedCentralGoogle Scholar
  104. Mulinacci N, Prucher D, Peruzzi M et al (2004) Commercial and laboratory extracts from artichoke leaves: estimation of caffeoyl esters and flavonoidic compounds content. J Pharm Biomed Anal 34:349–357. CrossRefPubMedGoogle Scholar
  105. Navarre DA, Pillai SS, Shakya R, Holden MJ (2011) HPLC profiling of phenolics in diverse potato genotypes. Food Chem 127:34–41. CrossRefGoogle Scholar
  106. Newman DJ, Cragg GM (2012) Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 75:311–335. CrossRefPubMedPubMedCentralGoogle Scholar
  107. Niggeweg R, Michael AJ, Martin C (2004) Engineering plants with increased levels of the antioxidant chlorogenic acid. Nat Biotechnol 22:746–754. CrossRefPubMedGoogle Scholar
  108. Noldin VF, Filho VC, Monache FD et al (2003) Composição química e actividades biológicas das folhas de Cynara scolymus L. (alcachofra) cultivada no Brasil (chemical composition and biological activities of the leaves of Cynara scolymus L. (artichoke) cultivated in Brazil). Quím Nova 26:331–334. CrossRefGoogle Scholar
  109. Padilla-Gonzalez GF, dos Santos FA, Da Costa FB (2016) Sesquiterpene lactones: more than protective plant compounds with high toxicity. CRC Crit Rev Plant Sci 35:18–37. CrossRefGoogle Scholar
  110. Pandino G, Courts FL, Lombardo S et al (2010) Caffeoylquinic acids and flavonoids in the immature inflorescence of globe artichoke, wild cardoon, and cultivated cardoon. J Agric Food Chem 58:1026–1031. CrossRefPubMedGoogle Scholar
  111. Pandino G, Lombardo S, Mauromicale G, Williamson G (2011a) Profile of polyphenols and phenolic acids in bracts and receptacles of globe artichoke (Cynara cardunculus var. scolymus) germplasm. J Food Compos Anal 24:148–153. CrossRefGoogle Scholar
  112. Pandino G, Lombardo S, Mauromicale G, Williamson G (2011b) Phenolic acids and flavonoids in leaf and floral stem of cultivated and wild Cynara cardunculus L. genotypes. Food Chem 126:417–422. CrossRefGoogle Scholar
  113. Pandino G, Lombardo S, Moglia A et al (2015) Leaf polyphenol profile and SSR-based fingerprinting of new segregant Cynara cardunculus genotypes. Front Plant Sci 5:1–10. CrossRefGoogle Scholar
  114. Patridge E, Gareiss P, Kinch MS, Hoyer D (2016) An analysis of FDA-approved drugs: natural products and their derivatives. Drug Discov Today 21:204–207. CrossRefPubMedGoogle Scholar
  115. Pauwels EKJ (2011) The protective effect of the Mediterranean diet: focus on cancer and cardiovascular risk. Med Princ Pract 20:103–111. CrossRefPubMedGoogle Scholar
  116. Payyavula RS, Shakya R, Sengoda VG et al (2015) Synthesis and regulation of chlorogenic acid in potato: rerouting phenylpropanoid flux in HQT-silenced lines. Plant Biotechnol J 13:551–564. CrossRefPubMedGoogle Scholar
  117. Pinelli P, Agostini F, Comino C et al (2007) Simultaneous quantification of caffeoyl esters and flavonoids in wild and cultivated cardoon leaves. Food Chem 105:1695–1701. CrossRefGoogle Scholar
  118. Pistón M, Machado I, Branco CS et al (2014) Infusion, decoction and hydroalcoholic extracts of leaves from artichoke (Cynara cardunculus L. subsp. cardunculus) are effective scavengers of physiologically relevant ROS and RNS. Food Res Int 64:150–156. CrossRefPubMedGoogle Scholar
  119. Prior RL, Wu XL, Schaich K (2005) Standardized methods for the determination of antioxidant capacity and phenolics in foods and dietary supplements. J Agric Food Chem 53:4290–4302. CrossRefPubMedGoogle Scholar
  120. Proença da Cunha A, da Silva AP, Roque OR (2009) Alcachofra (Artichoke). In: Fundação Calouste Gulbenkian (ed) Plantas e produtos vegetais em fitoterapia (Plants and vegetable products in phytotherapy). Fundação Calouste Gulbenkian, Lisbon, pp 86–87Google Scholar
  121. Pulido R, Bravo L, Saura-Calixto F (2000) Antioxidant activity of dietary polyphenols as determined by a modified ferric reducing/antioxidant power assay. J Agric Food Chem 48:3396–3402. CrossRefPubMedGoogle Scholar
  122. Rabi T, Bishayee A (2009) Terpenoids and breast cancer chemoprevention. Breast Cancer Res Treat 115:223–239. CrossRefPubMedGoogle Scholar
  123. Raccuia SA, Mainolfi A, Mandolino G, Melilli MG (2004) Genetic diversity in Cynara cardunculus revealed by AFLP markers: comparison between cultivars and wild types from Sicily. Plant Breed 123:280–284. CrossRefGoogle Scholar
  124. Ramos PAB, Guerra ÂR, Guerreiro O et al (2013) Lipophilic extracts of Cynara cardunculus L. var. altilis (DC): a source of valuable bioactive terpenic compounds. J Agric Food Chem 61:8420–8429. CrossRefPubMedGoogle Scholar
  125. Ramos P, Guerra A, Guerreiro O et al (2014a) Antitumoral and antioxidant activities of lipophilic and phenolic extracts from Cynara cardunculus L. var. altilis (DC). Planta Med 80:P1L16. CrossRefGoogle Scholar
  126. Ramos PAB, Santos SAO, Guerra ÂR et al (2014b) Phenolic composition and antioxidant activity of different morphological parts of Cynara cardunculus L. var. altilis (DC). Ind Crops Prod 61:460–471. CrossRefGoogle Scholar
  127. Ramos PAB, Guerra ÂR, Guerreiro O et al (2017) Antiproliferative effects of Cynara cardunculus L. var. altilis (DC) lipophilic extracts. Int J Mol Sci 18:63. CrossRefGoogle Scholar
  128. Reddy L, Odhav B, Bhoola KD (2003) Natural products for cancer prevention: a global perspective. Pharmacol Ther 99:1–13. CrossRefPubMedGoogle Scholar
  129. Rial C, Novaes P, Varela RM et al (2014) Phytotoxicity of cardoon (Cynara cardunculus) allelochemicals on standard target species and weeds. J Agric Food Chem 62:6699–6706. CrossRefPubMedGoogle Scholar
  130. Roseiro LB, Barbosa M, Ames JM, Wilbey RA (2003) Cheesemaking with vegetable coagulants—the use of Cynara L. for the production of ovine milk cheeses. Int J Dairy Technol 56:76–85. CrossRefGoogle Scholar
  131. Rottenberg A (2014) The wild gene pool of globe artichoke. Isr J Plant Sci 62:1–6. CrossRefGoogle Scholar
  132. Rottenberg A, Zohary D (1996) The wild ancestor of the cultivated artichoke. Genet Resour Crop Evol 43:53–58. CrossRefGoogle Scholar
  133. Rottenberg A, Zohary D, Nevo E (1996) Isozyme relationships between cultivated artichoke and the wild relatives. Genet Resour Crop Evol 43:59–62. CrossRefGoogle Scholar
  134. Rouphael Y, Bernardi J, Cardarelli M et al (2016) Phenolic compounds and sesquiterpene lactones profile in leaves of nineteen artichoke cultivars. J Agric Food Chem 64:8540–8548. CrossRefPubMedGoogle Scholar
  135. Saénz Rodriguez T, Garcia Gimenez D, de la Puerta Vazquez R (2002) Choleretic activity and biliary elimination of lipids and bile acids induced by an artichoke leaf extract in rats. Phytomedicine 9:687–693. CrossRefPubMedGoogle Scholar
  136. Sarmento AC, Lopes H, Oliveira CS et al (2009) Multiplicity of aspartic proteinases from Cynara cardunculus L. Planta 230:429–439. CrossRefPubMedGoogle Scholar
  137. Schmidt TJ (1999) Toxic activities of sesquiterpene lactones: structural and biochemical aspects. Curr Org Chem 3:577–608Google Scholar
  138. Schneider G, Thiele KI (1974) The distribution of the bitter principle cynaropicrine in Cynara. Planta Med 26:174–183. CrossRefGoogle Scholar
  139. Schütz K, Kammerer D, Carle R et al (2004) Identification and quantification of caffeoylquinic acids and flavonoids from artichoke (Cynara scolymus L.) heads, juice and pomace by HPLC-DAD-ESI/MSn. J Agric Food Chem 52:4090–4096. CrossRefPubMedGoogle Scholar
  140. Sengo I, Gominho J, D’Orey L et al (2010) Response surface modeling and optimization of biodiesel production from Cynara cardunculus oil. Eur J Lipid Sci Technol 112:310–320. CrossRefGoogle Scholar
  141. Shimizu S, Ishihara N, Umehara K et al (1988) Sesquiterpene glycosides and saponins from Cynara cardunculus L. Chem Pharm Bull 36:2466–2474CrossRefGoogle Scholar
  142. Shimoda H, Ninomiya K, Nishida N et al (2003) Anti-hyperlipidemic sesquiterpenes and new sesquiterpene glycosides from the leaves of artichoke (Cynara scolymus L.): structure requirement and mode of action. Bioorg Med Chem Lett 13:223–228. CrossRefPubMedGoogle Scholar
  143. Sonnante G, Pignone D, Hammer K (2007) The domestication of artichoke and cardoon: from Roman times to the genomic age. Ann Bot 100:1095–1100. CrossRefPubMedPubMedCentralGoogle Scholar
  144. Sonnante G, D’Amore R, Blanco E et al (2010) Novel hydroxycinnamoyl-coenzyme A quinate transferase genes from artichoke are involved in the synthesis of chlorogenic acid. Plant Physiol 153:1224–1238. CrossRefPubMedPubMedCentralGoogle Scholar
  145. Sonnante G, Gatto A, Morgese A et al (2011) Genetic map of artichoke x wild cardoon: toward a consensus map for Cynara cardunculus. Theor Appl Genet 123:1215. CrossRefPubMedGoogle Scholar
  146. Soumaya K, Chaouachi F, Ksouri R, El Gazzah M (2013) Polyphenolic composition in different organs of Tunisia populations of Cynara cardunculus L. and their antioxidant activity. J Food Nutr Res 1:1–6. CrossRefGoogle Scholar
  147. St-Pierre B, De Luca V (2000) Chapter Nine—evolution of acyltransferase genes: origin and diversification of the BAHD superfamily of acyltransferases involved in secondary metabolism. Recent Adv Phytochem 34:285–315. CrossRefGoogle Scholar
  148. Sun C-L, Yuan J-M, Koh W-P, Yu MC (2006) Green tea, black tea and breast cancer risk: a meta-analysis of epidemiological studies. Carcinogenesis 27:1310–1315. CrossRefPubMedGoogle Scholar
  149. Takahama U, Hirotsu M, Oniki T (1999) Age-dependent changes in levels of ascorbic acid and chlorogenic acid, and activities of peroxidase and superoxide dismutase in the apoplast of tobacco leaves: mechanism of the oxidation of chlorogenic acid in the apoplast. Plant Cell Physiol 40:716–724. CrossRefGoogle Scholar
  150. Tamagnone L, Merida A, Parr A et al (1998) The AmMYB308 and AmMYB330 transcription factors from antirrhinum regulate phenylpropanoid and lignin biosynthesis in transgenic tobacco. Plant Cell 10:135–154. CrossRefPubMedPubMedCentralGoogle Scholar
  151. Taylor R (1990) Interpretation of the correlation coefficient: a basic review. J Diagn Med Sonogr 6:35–39. CrossRefGoogle Scholar
  152. Terpinc P, Abramovič H (2010) A kinetic approach for evaluation of the antioxidant activity of selected phenolic acids. Food Chem 121:366–371. CrossRefGoogle Scholar
  153. Upadhyay R, Rao LJM (2013) An outlook on chlorogenic acids-occurrence, chemistry, technology, and biological activities. Crit Rev Food Sci Nutr 53:968–984. CrossRefPubMedGoogle Scholar
  154. Valentão P, Fernandes E, Carvalho F et al (2002) Antioxidative properties of cardoon (Cynara cardunculus L.) infusion against superoxide radical, hydroxyl radical, and hypochlorous acid. J Agric Food Chem 50:4989–4993. CrossRefPubMedGoogle Scholar
  155. Velez Z, Campinho M, Guerra  et al (2012) Biological characterization of Cynara cardunculus L. methanolic extracts: antioxidant, anti-proliferative, anti-migratory and anti-angiogenic activities. Agriculture 2:472–492. CrossRefGoogle Scholar
  156. Veríssimo P, Esteves C, Faro C, Pires E (1995) The vegetable rennet of Cynara cardunculus L. contains two proteinases with chymosin and pepsin-like specificities. Biotechnol Lett 17:621–626. CrossRefGoogle Scholar
  157. Villegas RJ, Kojima M (1986) Purification and characterization of hydroxycinnamoyl d-glucose. Quinate hydroxycinnamoyl transferase in the root of sweet potato, Ipomoea batatas Lam. J Biol Chem 261:8729–8733PubMedGoogle Scholar
  158. Wang MF, Simon JE, Aviles IF et al (2003) Analysis of antioxidative phenolic compounds in artichoke (Cynara scolymus L.). J Agric Food Chem 51:601–608. CrossRefPubMedGoogle Scholar
  159. Wiklund A (1992) The genus Cynara L. (Asteraceae-Cardueae). Bot J Linn Soc 109:75–123. CrossRefGoogle Scholar
  160. World Health Organization (2002) WHO traditional medicine strategy 2002–2005. WHO, Geneva. Cited 24 January 2019
  161. World Health Organization (2014) Antimicrobial resistance: global report on surveillance 2014. WHO, Geneva.;jsessionid=0614D9965AAD9BCAC21A118884B41A66?sequence=1. Cited 24 January 2019
  162. Yasukawa K, Matsubara H, Sano Y (2010) Inhibitory effect of the flowers of artichoke (Cynara cardunculus) on TPA-induced inflammation and tumor promotion in two-stage carcinogenesis in mouse skin. J Nat Med 64:388–391. CrossRefPubMedGoogle Scholar
  163. Zhu XF, Zhang HX, Lo R (2004) Phenolic compounds from the leaf extract of artichoke (Cynara scolymus L.) and their antimicrobial activities. J Agric Food Chem 52:7272–7278. CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.CICECO and Department of ChemistryUniversity of AveiroAveiroPortugal
  2. 2.Centro de Biotecnologia Agrícola e Agro-Alimentar do Alentejo (CEBAL)/Instituto Politécnico de Beja (IPBeja)BejaPortugal
  3. 3.Instituto de Ciências Agrárias e Ambientais Mediterrânicas (ICAAM)Universidade de ÉvoraÉvoraPortugal
  4. 4.Instituto de Tecnologia Química e Biológica António XavierUniversidade Nova de Lisboa (ITQB Nova)OeirasPortugal
  5. 5.Wellcome Sanger InstituteCambridgeUK

Personalised recommendations