Thidiazuron as an Elicitor in the Production of Secondary Metabolite

  • Bengu Turkyilmaz Unal


The secondary metabolites are known to play a major role in the adaptation of plants to their environment. They are also used by humans as food additives and as pharmaceuticals. Various strategies have been developed to improve the production of secondary metabolites in plant cell and tissue culture. Strain improvement, methods for the selection of high-producing cell lines, medium optimizations, and treatment of the undifferentiated cells with abiotic or biotic elicitors such as heavy metals, chitosan, methyljasmonate, salicylic acid, and thidiazuron (TDZ) can lead to an enhancement in secondary metabolite production. TDZ, a substituted phenylurea (N-phenyl-1,2,3-thiadiazol-5-yl urea), has gained a considerable attention during the past decades due to its efficient role in plant cell and tissue culture. TDZ has shown both auxin- and cytokinin-like effects, although, chemically, it is totally different from commonly used auxins and cytokinins. A number of physiological and biochemical events in cells are induced or enhanced by TDZ. To attain continuous and quick industrial production, when used in the appropriate concentration, the addition of stimulants such as TDZ to the growing medium will contribute to production of secondary metabolites.


Biotechnology Cytokinin Natural products Pharmaceutical plants TDZ 


  1. Alatar AA (2015) Thidiazuron induced efficient in vitro multiplication and ex vitro conservation of Rauvolfia serpentina – a potent antihypertensive drug producing plant. Biotechnol Biotechnol Equip 29(3):489–497Google Scholar
  2. Arndt FR, Rusch R, Stillfried HV, Hanisch B, Martin WC (1976.) SN 49537) A new cotton defoliant. Plant Physiol 57(5):99Google Scholar
  3. Balandrin MF, Klocke JA (1988) Medicinal, aromatic and industrial materials from plants. In: Bajaj YPS (ed) Biotechnology in agriculture and forestry, vol 40. Springer, Berlin, pp 1–35Google Scholar
  4. Barz W, Ellis B (1981) Potential of plant cell cultures for pharmaceutical production. In: Beal JL, Reinhard E (eds) Natural products as medicinal agents. Hippokrates, Stuttgart, pp 471–507Google Scholar
  5. Barz W, Daniel S, Hinderer W, Jaques U, Kessmann H, Koster J, Tiemann K (1988) Elicitation and metabolism of phytoalexins in plant cell cultures. In: Pais M, Deus B, Zenk MH (eds) Exploitation of plant cells for the production of natural compounds. Biotechnol Bioeng 1982, 24:1965–1974Google Scholar
  6. Baskaran P, Ncube B, Van Staden J (2012) In vitro propagation and secondary product production by Merwilla plumbea (Lindl.) Spet. Plant Growth Regul 67:235Google Scholar
  7. Dhavala A, Rathore TS (2010) Micropropagation of Embelia ribes Burm f. through proliferation of adult plant axillary shoots. In: Vitro Cell Dev Bio Plant 46, pp 180–191Google Scholar
  8. Deus B, Zenk MH (1982) Exploitation of plant cells for the production of natural compounds. Biotechnol Bioeng 24:1965–1974CrossRefPubMedGoogle Scholar
  9. Dicosmo F, Misawa M (1985) Eliciting secondary metabolism in plant cell cultures. Trends Biotechnol 3:318–322CrossRefGoogle Scholar
  10. Dicosmo F, Tallevi SG (1985) Plant cell cultures and microbial insult: interactions with biotechnological potential. Trends Biotechnol 3:110–111CrossRefGoogle Scholar
  11. Dixon RA (2001) Natural products and plant disease resistance. Nature 411:843–847CrossRefPubMedGoogle Scholar
  12. Eilert U (1987) Elicitation: methodology and aspects of application. In: Constabel F, Vasil I (eds) Cell culture and somatic cell genetics of plants, vol 4. Academic, San Diego, pp 153–196Google Scholar
  13. Eilert U, Kurz WGW, Constabel F (1985) Stimulation of sanguinarine accumulation in Papaver somniferum cell cultures by fungal elicitors. J Plant Physiol 119:65–76Google Scholar
  14. Fujita Y, Tabata M (1987) Secondary metabolites from plant cells – pharmaceutical applications and progress in commercial production. In: Green CE et al (eds) Plant tissue and cell culture. Alan R. Liss, New York, pp 169–185Google Scholar
  15. Grzegorczyk-Karolak I, Kuzma L, Wysokinska H (2015) The effect of cytokinins on shoot proliferation, secondary metabolite production and antioxidant potential in shoot cultures of Scutellaria alpina. Plant Cell Tissue Organ Cult 122:699–708CrossRefGoogle Scholar
  16. Guo B, Abbasi BH, Zeb A, Xu LL, Wei YH (2011) TDZ: a multi-dimensional plant growth regulator. Afr J Biotechnol 10:8984–9000CrossRefGoogle Scholar
  17. Hosseini-Nasr M, Rashid A (2000) Thidiazuron-induced shoot-bud formation on root segments of Albizia julibrissin is an apex-controlled, light-independent and calcium-mediated response. Plant Growth Regul 36:81–85Google Scholar
  18. Islam A, Selvan T, Mazumdar UK, Gupta M, Ghosal S (2008) Antitumor effect of phyllanthin and hypophyllanthin from Phyllanthus amarus against ehrlich ascites carcinoma in mice. Pharmacol Online 2:796–807Google Scholar
  19. Islek C, Turkyilmaz UB, Koc E, Kaya D (2016) Effect of thidiazuron used as an elicitor in the production of capsaicin on total protein and phenolic amounts, antioxidant enzyme activities of pepper plants. Int J Environ Agric Biotechnol (IJEAB) 1(3):603–609CrossRefGoogle Scholar
  20. Jha S, Sahu NP, Mahato SB (1988) Production of the alkaloids emetine and cephaeline in callus cultures of Cephaelis ipecacuanha. Planta Med 54:504–506CrossRefPubMedGoogle Scholar
  21. Johnson TS, Ravishankar GA, Venkataraman LV (1991) Elicitation of capsaicin production in freely suspended cells and immobilized cell cultures of Capsicum frutescens Mill. Food Biotechnol 5:197–205CrossRefGoogle Scholar
  22. Karuppusamy S (2009) A review on trends in production of secondary metabolites from higher plants by in vitro tissue, organ and cell cultures. J Med Plants Res 3(13):1222–1239Google Scholar
  23. Katzung BG (1995) Basic and clinical pharmacology, 6th edn. Prentice Hall International (UK) Limited, LondonGoogle Scholar
  24. Khan H, Siddique I, Anis M (2006) Thidiazuron induced somatic embryogenesis and plant regeneration in Capsicum annuum. Biol Plant 50:789–792CrossRefGoogle Scholar
  25. Kiemer AK, Hartung T, Huber C, Vollmar AM (2003) Phyllanthus amarus has anti-inflammatory potential by inhibition of iNOS, COX2, and cytokines via the NF-jB pathway. J Hepatol 38(3):289–297CrossRefPubMedGoogle Scholar
  26. Kumar KBH, Kuttan R (2005) Chemoprotective activity of an extract of Phyllanthus amarus against cyclophosphamide induced toxicity in mice. Phytomedicine 12(6–7):494–500CrossRefPubMedGoogle Scholar
  27. Kumar P, Srivastava DK (2015) Effect of potent cytokinin thidiazuron on in vitro morphogenic potential of broccoli (Brassica oleracea L. var. italica), an important vegetable crop. Indian J Plant Physiol 20(4):317–323CrossRefGoogle Scholar
  28. Li H, Murch SJ, Saxena PK (2000) Thidiazuron-induced de novo shoot organogenesis on seedlings, etiolated hypocotyls and stem segments of Huang-qin. Plant Cell Tissue Organ Cult 62:169–173CrossRefGoogle Scholar
  29. Matand K, Prakash CS (2007) Evaluation of peanut genotypes for in vitro plant regeneration using thidiazuron. J Biotechnol 130:202–207CrossRefPubMedGoogle Scholar
  30. Mok MC, Mok DWS, Armstrong DJ, Shudo K, Isogai Y, Okamoto T (1982) Cytokinin activity of N-phenyl-N1-1,2,3-thiadiazol-5-ylurea (Thidiazuron). Phytochemistry 21:1509–1511CrossRefGoogle Scholar
  31. Mulabagal V, Tsay HS (2004) Plant cell cultures – an alternative and efficient source for the production of biologically important secondary metabolites. Int J Appl Sci Eng 2:29–48Google Scholar
  32. Murthy S (1997) Morpho-physiological role of thidiazuron in plants. PhD thesis, University of Guelph, CanadaGoogle Scholar
  33. Namdeo AG (2007) Plant cell elicitation for production of secondary metabolites: a review. Pharmacogn Rev 1(1):69–79Google Scholar
  34. Nigra HM, Caso OH, Guilietti AM (1987) Production of solasodine by calli form different parts of Solanum elaeagnifolium Cav plants. Plant Cell Rep 6:135–137PubMedGoogle Scholar
  35. Oksman-Caldenteyl KM, Inze D (2004) Plant cell factories in the post-genomic era: new ways to produce designer secondary metabolites. Trends Plant Sci 9:9Google Scholar
  36. Pezzuto J (1996) Taxol® production in plant cell culture comes of age. Nat Biotechnol 14:1083CrossRefPubMedGoogle Scholar
  37. Radman R, Saez T, Bucke C, Keshavarz T (2003) Elicitation of plant and microbial systems. Biotechnol Appl Biochem 37:91–102CrossRefPubMedGoogle Scholar
  38. Rai V, Mehrotra S (2007) Chromium-induced changes in ultramorphology and secondary metabolites of Phyllanthus amarus Schum & Thonn.— an hepatoprotective plant. Environ Monit Assess 147:307–315CrossRefGoogle Scholar
  39. Rao RS, Ravishankar GA (2002) Plant tissue cultures; chemical factories of secondary metabolites. Biotechnol Adv 20:101–153CrossRefPubMedGoogle Scholar
  40. Roberts MF (1988) Medicinal products through plant biotechnology. In: Robins RJ, Rhodes MJC (eds) Manipulating secondary metabolism in culture. University Press, Cambridge, pp 201–216Google Scholar
  41. San B, Karakurt Y, Donmez F (2015) Effects of Thidiazuron and activated charcoal on in vitro shoot proliferation and rooting of Myrtle (Myrtus communis L.) J Agric Sci 21(2):177–183Google Scholar
  42. Santos A, Campos R, Miguel O, Filho V, Siani A, Yunes R, Calixto J (2000) Antinociceptive properties of extracts of new species of plants of the genus Phyllanthus (Euphorbiaceae). J Ethnopharmacol 72:229–238Google Scholar
  43. Shang XF, He XR, He XY, Li MX, Zhang RX, Fan PC, Zhang QL, Jia ZP (2010) The genus Scutellaria an ethnopharmacological and phytochemical review. J Ethnopharmacol 128:279–313Google Scholar
  44. Sharma PC, Yelne MB, Dennis TJ (2001) Database on medicinal plants used in ayurveda, vol 3. Central Council for Research in Ayurveda and Siddha, Delhi, pp 512–536Google Scholar
  45. Siddique I, Anis A (2007) Rapid micropropagation of Ocimum Basilicum using shoot tip explants precultured in thidiazuron supplemented liquid medium. Biol Plant 51:787–790CrossRefGoogle Scholar
  46. Svetla DY, Sara G, Ervin F, Simcha LY, Moshe AF (2003) Auxin type and timing of application determine the activation of the developmental program during in vitro organogenesis in apple. Plant Sci 165:299–309CrossRefGoogle Scholar
  47. Toppel G, Witte L, Riebesehl B, Von Borstel K, Hartman T (1987) Alkaloid patterns and biosynthetic capacity of root cultures from some pyrrolizidine alkaloid producing Senecio spp. Plant Cell Rep 6:466–469PubMedGoogle Scholar
  48. Tripathi F, Tripathi JN (2003) Role of biotechnology in medicinal plants. Trop J Pharm Res 2(2):243–253Google Scholar
  49. Ulbrich B, Wiesner W, Arens H (1985) Large scale production of rosmarinic acid from plant cell cultures of Coleus blumei Benth. In: Neumann KH et al (eds) Primary and secondary metabolism of plant cell cultures. Springer, Berlin, pp 293–303CrossRefGoogle Scholar
  50. Unander DW, Webster GL, Blumberg BS (1995) Usage and bioassays in Phyllanthus (Euphorbiaceae). IV. Clustering of antiviral uses and other effects. J Ethnopharmacol 45:1–18Google Scholar
  51. Verpoorte R, Contin A, Memelink J (2002) Phytochem Rev 1:13. CrossRefGoogle Scholar
  52. Vijaya SN, Udayasri PVV, Aswani KY, Ravi BB, Phani PY, Vijay VM (2010) Advancements in the production of secondary metabolites. J Nat Prod 3:112–123Google Scholar
  53. Wink M, Alfermann AW, Franke R, Wetterauer B, Distl M, Windhovel J, Krohn O, Fuss E, Garden H, Mohagheghzaden A, Wildi E, Ripplinger P (2005) Sustainable bioproduction of phytochemicals by plant in vitro cultures: anticancer agents. Plant Genet Resour 3:90–100CrossRefGoogle Scholar
  54. Wyk BEV, Wink M (2004) Medicinal plants of the world. Briza, PretoriaGoogle Scholar
  55. Yeoman MM, Yeoman CL (1996) Tansley review no. 90 manipulating secondary metabolism in cultured plant cells. New Phytol 134:553–569CrossRefGoogle Scholar
  56. Zhao J, Zhu WH, Hu Q, Guo YQ (2001) Compact callus cluster suspension cultures of Catharanthus roseus with enhanced indole alkaloid biosynthesis. In-vitro Cell Dev Biol-Plant 37:68–72CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.Arts and Sciences Faculty, Biotechnology DepartmentNigde Omer Halisdemir UniversityNigdeTurkey

Personalised recommendations