Paulownia C-geranylated flavonoids: their structural variety, biological activity and application prospects

  • Chun-lei Cheng
  • Xian-hui Jia
  • Cheng-mei Xiao
  • Wen-zhao TangEmail author


Paulownia species, especially their flowers and fruits, are traditionally used in Chinese herbal medicines for the treatment of infectious diseases. C-geranylated flavonoids were found to be the major special metabolites in Paulownia flowers and fruits, and 76 C-geranylated flavonoids had been isolated and characterized thus far. Structural variations in Paulownia C-geranylated flavonoids are mainly due to the complicated structural modifications in their geranyl substituents. These natural compounds have attracted much attention because of their various biological activities, including antioxidation, anti-inflammation, cytotoxic activity and various enzymatic inhibitions, etc. Among them, diplacone, a major Paulownia component, was considered to have promise for applications in medicine. This paper summarizes the information from current publications on Paulownia C-geranylated flavonoids, with a focus on their structural variety, key spectroscopic characteristics, biological activity with structure–activity relationships and application prospects. We hope that this paper will stimulate further investigations of Paulownia species and this kind of natural product.


Paulownia species C-geranylated flavonoids Phytochemistry Biological properties 



This work was financially supported by the Innovation Project of Shandong Academy of Medical Sciences (2019), the Science Development Project of Shandong Academy of Medical Science (2015-08) and the Natural Science Open Foundation of State Key Laboratory of Bioactive Substances and Function of Natural Medicines (GTZK201503).


  1. Alcaráz LE, Blanco SE, Puig ON et al (2000) Antibacterial activity of flavonoids against methicillin-resistant Staphylococcus aureus strains. J Theor Biol 205:231–240CrossRefGoogle Scholar
  2. Andersen OM, Markham KR (2006) Flavonoids: chemistry, biochemistry, applications. CRC Press, Boca RatonGoogle Scholar
  3. Asai T, Hara N, Kobayashi S et al (2008) Geranylated flavanones from the secretion on the surface of the immature fruits of Paulownia tomentosa. Phytochemistry 69:1234–1241CrossRefGoogle Scholar
  4. Barron D, Ibrahim RK (1996) Isoprenylated flavonoids—a survey. Phytochemistry 43:921–982CrossRefGoogle Scholar
  5. Barron D, Pietro AD, Dumontet C et al (2002) Isoprenoid flavonoids are new leads in the modulation of chemoresistance. Phytochem Rev 1:325–332CrossRefGoogle Scholar
  6. Bergmann BA (1998) Propagation method influences first year field survival and growth of Paulownia. New Forest 16:251–264CrossRefGoogle Scholar
  7. Bruno F, Spaziano G, Liparulo A et al (2018) Recent advances in the search for novel 5-lipoxygenase inhibitors for the treatment of asthma. Eur J Med Chem 153:65–72CrossRefGoogle Scholar
  8. Cao G, Sofic E, Prior RL (1997) Antioxidant and prooxidant behavior of flavonoids: structure-activity relationships. Free Radical Biol Med 22:749–760CrossRefGoogle Scholar
  9. Chen J, Liu Y, Shi YP (2009) Determination of flavonoids in the flowers of Paulownia tomentosa by high-performance liquid chromatography. J Anal Chem 64:282–288CrossRefGoogle Scholar
  10. Chen R, Gao BQ, Liu X et al (2017a) Molecular insights into the enzyme promiscuity of an aromatic prenyltransferase. Nat Chem Biol 13:226–234CrossRefGoogle Scholar
  11. Chen HN, Tang WZ, Yan ZH et al (2017b) Protective effect of diplacone on vascular endothelial injury induced by homocysteine. Chin J Arterioscler 25:666–670Google Scholar
  12. Chinese Flora Editorial Committee (1998) Flora of China, Paulownia Siebold & Zuccarini. Chinese Academy of Sciences, Beijing,
  13. Cho JK, Ryu YB, Curtis-Long MJ et al (2012) Cholinestrase inhibitory effects of geranylated flavonoids from Paulownia tomentosa fruits. Bioorgan Med Chem 20:2595–2602CrossRefGoogle Scholar
  14. Cho JK, Curtis-Long MJ, Lee KH et al (2013) Geranylated flavonoids displaying SARS-CoV papain-like protease inhibition from the fruits of Paulownia tomentosa. Bioorg Med Chem 21:3051–3057CrossRefGoogle Scholar
  15. Duan WD, Zhang J, Xie G et al (2007) Chemical constituents from the flower of Paulownia fortune (Seem) Hemsl. J Chin Med Mater 30:168–170Google Scholar
  16. Dugas AJ, Castaneda-Acosta J, Bonin GC et al (2000) Evaluation of the total peroxyl radical scavenging capacity of flavonoids: structure-activity relationships. J Nat Prod 63:327–331CrossRefGoogle Scholar
  17. Erbar C, Gülden C (2011) Ontogeny of the flowers in Paulownia tomentosa-a contribution to the recognition of the resurrected monogeneric family Paulowniaceae. Flora 206:205–218CrossRefGoogle Scholar
  18. Gang DR, Beuerle T, Ullmann P et al (2002) Differential production of meta hydroxylated phenylpropanoids in sweet basil peltate glandular trichomes and leaves is controlled by the activities of specific acyltransferases and hydroxylases. Plant Physiol 130:1536–1544CrossRefGoogle Scholar
  19. Gao TY, Jin X, Tang WZ et al (2015) New geranylated flavanones from the fruits of Paulownia catalpifolia Gong Tong with their anti-proliferative activity on lung cancer cells A549. Bioorgan Med Chem Lett 25:3686–3689CrossRefGoogle Scholar
  20. Hanáková Z, Hošek J, Babula P et al (2015) C-Geranylated flavanones from Paulownia tomentosa fruits as potential anti-inflammatory compounds acting via inhibition of TNF-α production. J Nat Prod 78:850–863CrossRefGoogle Scholar
  21. Hanáková Z, Hošek J, Kutil Z et al (2017) Anti-inflammatory activity of natural geranylated flavonoids: cyclooxygenase and lipoxygenase inhibitory properties and proteomic analysis. J Nat Prod 80:999–1006CrossRefGoogle Scholar
  22. He T, Vaidya BN, Perry ZD et al (2016) Paulownia as a medicinal tree: traditional uses and current advances. Eur J Med Plants 14:1–15CrossRefGoogle Scholar
  23. Heim KE, Tagliaferro AR, Bobilya DJ (2002) Flavonoid antioxidants: chemistry, metabolism and structure activity relationships. J Nutr Biochem 13:572–584CrossRefGoogle Scholar
  24. Holubová P, Šmejkal K (2011) Changes in the level of bioactive compounds in Paulownia tomentosa fruits. J Liq Chromatogr Relat Technol 34:276–288CrossRefGoogle Scholar
  25. Hošek J, Závalová V, Šmejkal K et al (2010) Effect of diplacone on LPS-induced inflammatory gene expression in macrophages. Folia Biol (Praha) 56:124–130Google Scholar
  26. Hošek J, Toniolo A, Neuwirth O et al (2013) Prenylated and geranylated flavonoids increase production of reactive oxygen species in mouse macrophages but inhibit the inflammatory response. J Nat Prod 76:1586–1591CrossRefGoogle Scholar
  27. Hsu CL, Shyu MH, Lin JA et al (2011) Cytotoxic effects of geranyl flavonoid derivatives from the fruit of Artocarpus communisin SK-Hep-1 human hepatocellular carcinoma cells. Food Chem 127:127–134CrossRefGoogle Scholar
  28. Huang YL, Yeh PY, Shen CC et al (2003) Antioxidant flavonoids from the rhizomes of Helminthostachys zeylanica. Phytochemistry 64:1277–1283CrossRefGoogle Scholar
  29. Huang YC, Hwang TL, Yang YL et al (2010) Acetogenin and prenylated flavonoids from Helminthostachys zeylanica with inhibitory activity on superoxide generation and elastase release by neutrophils. Planta Med 76:447–453CrossRefGoogle Scholar
  30. Jiang TF, Du X, Shi YP (2004) Determination of flavonoids from Paulownia tomentosa (Thunb) Steud. by micellar electrokinetic capillary electrophoresis. Chromatographia 59:255–258Google Scholar
  31. Jin Q, Lee C, Lee JW et al (2015) Geranylated flavanones from Paulownia coreana and their inhibitory effects on nitric oxide production. Chem Pharm Bull 63:384–387CrossRefGoogle Scholar
  32. Kim SK, Cho SB, Moon HI (2010) Neuroprotective effects of a sesquiterpene lactone and flavanones from Paulownia tomentosa Steud. against glutamate-induced neurotoxicity in primary cultured rat cortical cells. Phytother Res 24:1898–1900CrossRefGoogle Scholar
  33. Kobayashi S, Asai T, Fujimoto Y et al (2008) Anti-herbivore structures of Paulownia tomentosa: morphology, distribution, chemical constituents and changes during shoot and leaf development. Ann Bot 101:1035–1047CrossRefGoogle Scholar
  34. Kollár P, Bárta T, Závalová V et al (2011) Geranylated flavanone tomentodiplacone B inhibits proliferation of human monocytic leukaemia (THP-1) cells. Brit J Pharmacol 162:1534–1541CrossRefGoogle Scholar
  35. Kuzuyama T, Noel JP, Richard SB (2005) Structural basis for the promiscuous biosynthetic prenylation of aromatic natural products. Nature 435:983–987CrossRefGoogle Scholar
  36. Li XQ, Wu JL, Cao FH et al (2008) Chemical constituents from leaves of Paulownia fortunei. J Chin Med Mater 31:850–852Google Scholar
  37. Liao CC (2016) Compounds for treating ocular diseases. US Patent 9,370,503 B1, 21 Jun 2016Google Scholar
  38. Lin JA, Wu CH, Fang SC et al (2012) Combining the observation of cell morphology with the evaluation of key inflammatory mediators to assess the anti-inflammatory effects of geranyl flavonoid derivatives in bread fruit. Food Chem 132:2118–2125CrossRefGoogle Scholar
  39. Lincoln DE (1980) Leaf resin flavonoids of Diplacus aurantiacus. Biochem Syst Ecol 8:397–400CrossRefGoogle Scholar
  40. Mabry TJ, Markham KR, Thomas MB (1969) The systematic identification of flavonoids. Springer, New YorkGoogle Scholar
  41. Moon HI, Jeong MH, Jo WS (2014) Protective activity of C-geranylflavonoid analogs from Paulownia tomentosa against DNA damage in 137Cs irradiated AHH-1 cells. Nat Prod Commun 9:1295–1298Google Scholar
  42. Moura FA, de Andrade KQ, dos Santos JCF et al (2015) Antioxidant therapy for treatment of inflammatory bowel disease: does it work. Redox Bio 6:617–639CrossRefGoogle Scholar
  43. Navrátilová A, Schneiderová K, Veselá D et al (2013) Minor C-geranylated flavanones from Paulownia tomentosa fruits with MRSA antibacterial activity. Phytochemistry 89:104–113CrossRefGoogle Scholar
  44. Navrátilová A, Nešuta O, Vančatová I et al (2016) C-Geranylated flavonoids from Paulownia tomentosa fruits with antimicrobial potential and synergistic activity with antibiotics. Pharm Biol 54:1398–1407CrossRefGoogle Scholar
  45. Ogungbe IV, Erwin WR, Setzer WN (2014) Antileishmanial phytochemical phenolics: molecular docking to potential protein targets. J Mol Graph Model 48:105–117CrossRefGoogle Scholar
  46. Ríos JL, Recio MC (2005) Medicinal plants and antimicrobial activity. J Ethnopharmacol 100:80–84CrossRefGoogle Scholar
  47. Ryu HW, Park YJ, Lee SU et al (2017) Potential anti-inflammatory effects of the fruits of Paulownia tomentosa. J Nat Prod 80:2659–2665CrossRefGoogle Scholar
  48. Salem MM, Capers J, Rito S et al (2011) Antiparasitic activity of C-geranyl flavonoids from Mimulus bigelovii. Phytother Res 25:1246–1249CrossRefGoogle Scholar
  49. Schneiderová K, Šmejkal K (2014) Phytochemical profile of Paulownia tomentosa (Thunb). Phytochem Rev, Steud. Google Scholar
  50. Schneiderová K, Šlapetová T, Hrabal R et al (2013) Tomentomimulol and mimulone B: two new C-geranylated flavonoids from Paulownia tomentosa fruits. Nat Prod Res 27:613–618CrossRefGoogle Scholar
  51. Sekher PA, Chan TS, O’Brien PJ et al (2001) Flavonoid B-ring chemistry and antioxidant activity: fast reaction kinetics. Biochem Biophys Res Commun 282:1161–1168CrossRefGoogle Scholar
  52. Slade D, Ferreira D, Marais JPJ (2005) Circular dichroism, a powerful tool for the assessment of absolute configuration of flavonoids. Phytochemistry 66:2177–2215CrossRefGoogle Scholar
  53. Šmejkal K (2014) Cytotoxic potential of C-prenylated flavonoids. Phytochem Rev 13:245–275CrossRefGoogle Scholar
  54. Smejkal K, Holubova P, Zima A et al (2007) Antiradical activity of Paulownia tomentosa (Scrophulariaceae) extracts. Molecules 12:1210–1219CrossRefGoogle Scholar
  55. Šmejkal K, Grycová L, Marek R et al (2007) C-Geranyl Compounds from Paulownia tomentosa fruits. J Nat Prod 70:1244–1248CrossRefGoogle Scholar
  56. Šmejkal K, Chudík S, Klouček P et al (2008a) Antibacterial C-geranylflavonoids from Paulownia tomentosa fruits. J Nat Prod 71:706–709CrossRefGoogle Scholar
  57. Šmejkal K, Babula P, Šlapetová T et al (2008b) Cytotoxic activity of C-geranyl compounds from Paulownia tomentosa fruits. Planta Med 74:1488–1491CrossRefGoogle Scholar
  58. Šmejkal K, Svačinová J, Šlapetová T et al (2010) Cytotoxic activities of several geranyl-substituted flavanones. J Nat Prod 73:568–572CrossRefGoogle Scholar
  59. Song YH, Uddin Z, Jin YM et al (2017) Inhibition of protein tyrosine phosphatase (PTP1B) and α-glucosidase by geranylated flavonoids from Paulownia tomentosa. J Enzyme Inhib Med Chem 32:1195–1202CrossRefGoogle Scholar
  60. Tang WZ, Wang YA, Gao TY et al (2017) Identification of C-geranylated flavonoids from Paulownia catalpifolia Gong Tong fruits by HPLC-DAD-ESI-MS/MS and their anti-aging effects on 2BS cells induced by H2O2. Chin J Nat Med 15:384–391Google Scholar
  61. Tsuchiya H, Iinuma M (2000) Reduction of membrane fluidity by antibacterial sophoraflavanone G isolated from Sophora exigua. Phytomedicine 7:161–165CrossRefGoogle Scholar
  62. Vochyánová Z, Bartošová L, Bujdáková V et al (2015) Diplacone and mimulone ameliorate dextran sulfate sodiuminduced colitis in rats. Fitoterapia 101:201–207CrossRefGoogle Scholar
  63. Wang YA, Xue J, Jia XH et al (2017) Chemical constituents from the fruit peel of Paulownia catalpifolia. J Chin Med Mater 40:1591–1595Google Scholar
  64. Wang YA, Guo X, Jia XH et al (2019) Undescribed C-geranylflavonoids isolated from the fruit peel of Paulownia catalpifolia T. Gong ex D.Y. Hong with their protection on human umbilical vein endothelial cells injury induced by hydrogen peroxide. Phytochemistry 158:126–134CrossRefGoogle Scholar
  65. Xing YL, Bi LW, Zhao ZD et al (2013) Research progress in plant resources and chemistry of Paulownia. Chem Ind For Prod 33:135–140Google Scholar
  66. Yazaki K, Sasaki K, Tsurumaru Y (2009) Prenylation of aromatic compounds, a key diversification of plant secondary metabolites. Phytochemistry 70:1739–1745CrossRefGoogle Scholar
  67. Zhang PF, Li C (2008) Flavones from flowers of Paulownia fortune. China J Chin Mater Med 33:2629–2632Google Scholar
  68. Zheng YZ, Deng G, Chen DF et al (2019) The influence of C2=C3 double bond on the antiradical activity of flavonoid: different mechanisms analysis. Phytochemistry 157:1–7CrossRefGoogle Scholar
  69. Zhu ZH, Chao CJ, Lu XY (1986) Paulownia in China: cultivation and utilization. Asian Network for Biological Science and International Development Research Centre, Chinese Academy of Forestry, BeijingGoogle Scholar
  70. Zima A, Hošek J, Treml J et al (2010) Antiradical and cytoprotective activities of several C-geranyl-substituted flavanones from Paulownia tomentosa fruit. Molecules 15:6035–6049CrossRefGoogle Scholar

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© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Shandong Institute for Food and Drug ControlJinanPeople’s Republic of China
  2. 2.Institute of Materia MedicaShandong Academy of Medical SciencesJinanPeople’s Republic of China
  3. 3.Key Laboratory for Biotech-Drugs Ministry of HealthJinanPeople’s Republic of China
  4. 4.Key Laboratory for Rare and Uncommon Diseases of Shandong ProvinceJinanPeople’s Republic of China

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