Genetic Engineering Potential of Hairy Roots of Poppy (Papaver spp.) for Production of Secondary Metabolites, Phytochemistry, and In Silico Approaches

  • Mala Trivedi
  • Aditi Singh
  • Parul Johri
  • Rachana Singh
  • Rajesh K. TiwariEmail author


Opium poppy is one of the most important medicinal plants, because of its secondary metabolites (alkaloids). Opium as such is an important product, which has many uses and abuses. Its alkaloids are widely used in modern pharmacopeia. Agrobacterium rhizogenes (hairy roots), mediated hairy root culture, is also used for secondary metabolite production under in vitro conditions. Hairy roots are able to grow fast without phytohormones and to produce the metabolites of the mother plant. India is the only country where UN has given license to produce opium from latex. The application of opiate alkaloids, mainly in hydrochloride, sulfate, and phosphate forms, is restricted in some well-defined therapeutic fields. A major component among alkaloids is morphine, having analgesic in nature and used mainly to control severe pain and sedative effects. Poppy seeds have been described as tonic and aphrodisiac, promote luster of the body, enhance capacity to muscular work, and allay nervous excitement. Plant of such economic importance is affected by various biotic and abiotic factors leading to yield loss. Biotic factors include fungi, bacteria, viruses, nematodes, and birds too. This important plant has huge prospects in pharma industry, and on other hand, it is facing lots of challenges in the form of illicit trade, drug abuse, and biotic and abiotic stresses.


Opium poppy Alkaloids Hairy root Secondary metabolite 


  1. Afzali, M., Ghaeli, P., Khanavi, M., Parsa, M., Montazeri, H., Ghahremani, M. H., & Ostad, S. N. (2006). Non-additive opium alkaloids selectively induced apoptosis in cancer cells compared to normal cells. Daru, 23, 16–23.CrossRefGoogle Scholar
  2. Allen, R. S., Millgate, A. G., Chitty, J. A., Thisleton, J., Miller, J. A., Fist, A. J., et al. (2004). RNAi-mediated replacement of morphine with the nonnarcotic alkaloid reticuline in opium poppy. Nature Biotechnology, 22, 1559–1566.
  3. Angerhofer, C. K., Guinaudeau, H., Wongpanich, V., Pezzuto, J. M., & Cordell, G. A. (1999). Antiplasmodial and cytotoxic activity of natural bisbenzylisoquinoline alkaloids. Journal of Natural Products, 62, 59–66.PubMedCrossRefGoogle Scholar
  4. Aoki, S., & Syono, K. (1999). Synergistic function of rolB, rolC, ORF13 and ORF14 of TL-DNA of agrobacterium rhizogenes in hairy root induction in Nicotiana tabacum. Plant & Cell Physiology, 40, 252–256.CrossRefGoogle Scholar
  5. Aruna, K., & Shivaramakrishnan, V. M. (1992). Anticarcinogenic effects of some Indian plants. Food and Chemical Toxicology, 30, 953–956.PubMedCrossRefGoogle Scholar
  6. Balbi, G. (1960). Poppy seed oil in manufacture of paints and varnishes. Oleria, 14, 97–104.Google Scholar
  7. Battersby, A. R., & Harper, B. J. T. (1958). Biogenesis of morphine. Chemistry and Industry (London), 2, 365–366.Google Scholar
  8. Belny, M., Herouart, D., Thomasset, B., David, H., Jacquin-Dubreuil, A., & David, A. (1997). Transformation of Papaver somniferum cell suspension cultures with sam-1 from A. thaliana results in cell lines of different S-adenosyl-L-methionine syn-thase activity. Physiologia Plantarum, 99, 233–240.CrossRefGoogle Scholar
  9. Benk, E. (1987). Seeds usable as nuts. Industrille Obst und Gemueseverwertung, 72, 282–284.Google Scholar
  10. Bentley, K. W., Boura, A. L., Fitzgerald, A. E., Hardy, D. G., McCoubrey, A., Aikman, M. L., & Lister, R. E. (1965). Compounds possessing morphine-Antagonising or powerful analgesic properties. Nature, 206, 102–103.PubMedCrossRefGoogle Scholar
  11. Bentley, K. W., Hardy, D. G., & Meek, B. (1967). Novel analgesics and molecular rearrangements in the morphine-thebaine group. II. Alcohols derived from 6,14-endo-etheno- and 6,14-endo-ethanotetrahydrothebaine. Journal of the American Chemical Society, 89(13), 3273–3280.PubMedCrossRefGoogle Scholar
  12. Berlin, J., Ruegenhagen, C., Dietze, P., Fecker, L. F., Goddijn, O. J. M., & Hoge, J. H. C. (1993). Increased production of serato-nin by suspension and root cultures of Peganum harmala transformed with a tryptophan decarboxylase cDNA clone from Cathranthus roseus. Transgenic Research, 2, 336–344.CrossRefGoogle Scholar
  13. Bernath, J. (1998). Poppy: The genus (Medicinal and Aromatic Plants. Industrial Profiles). Amsterdam: Harwood Academic Publishers.Google Scholar
  14. Berre, J. (1984). Relief of pain in intensive care patients. Resuscitation, 11(3–4), 157–164.PubMedCrossRefGoogle Scholar
  15. Binns, A. N., & Tomashow, J. V. (1988). Cell biology of agrobacterium infection and transformation of plants. Annual Review of Microbiology, 42, 575–606.CrossRefGoogle Scholar
  16. Blechert, S., Brodschelm, W., Holder, S., Kammerer, L., Kutchan, T. M., Mueller, M. J., Xia, Z. Q., & Zenk, M. H. (1995). The octadecanoid pathway: Signal molecules for the regulation of secondary pathways. Proceedings of the National Academy of Sciences, USA.Google Scholar
  17. Breall, J. A., Areosty, J. M., & Simons, M. (2005). Overview of the management of unstable angina and acute non-ST elevation (non-Q wave) myocardial infarction. Up To Date online, 12.3.Google Scholar
  18. Brillanceau, M. H., David, C., & Tempe, J. (1989). Genetic transformation of Catharanthus roseus G. Don by agrobacterium rhizogenes. Plant Cell Reports, 8, 63–66.PubMedCrossRefGoogle Scholar
  19. Camacho, M. D., Phillipson, D., Croft, S. L., Rock, P., Marshall, S. J., & Schiff, P. L., Jr. (2002). In vitro activity of Triclisia patens and some bisbenzylisoquinoline alkaloids against Leishmania donovani and Trypanosoma brucei brucei. Phytotherapy Research, 16, 432–436.CrossRefGoogle Scholar
  20. Chavadej, S., Brission, N., McNeil, J. N., & De, L. V. (1994). Redirection of tryptophan leads to production of low indole glucosinolate canola. Proceedings of the National Academy of Sciences of the United States of America, 91, 2166–2170.PubMedPubMedCentralCrossRefGoogle Scholar
  21. Chen, Q., Peng, W. L., Qi, S. J., & Xu, A. L. (2002). Apoptosis of human highly metastatic lung cancer cell line 95-D induced by acutiaporberine, a novel bisalkaloid derived from Thalictrum acutifolium. Planta Medica, 68, 550–553.PubMedCrossRefGoogle Scholar
  22. Cheney, R. H. (1964). Therapeutic potential of Eschscholtziae californicae herba. Quarterly Journal of Crude Drugs, 3, 413–416.CrossRefGoogle Scholar
  23. Chilton, M. D., Tepfer, D. A., Petit, A., David, C., Casse-Delbart, F., & Tempe, J. (1982). Agrobacterium rhizogenes inserts T-DNA into the genomes of the host plant root cells. Nature, 295, 432–434.CrossRefGoogle Scholar
  24. Christrup, L. L. (1997). Morphine metabolites. Acta Anaesthesiologica Scandinavica, 41(1 Pt 2), 116–122.PubMedCrossRefGoogle Scholar
  25. Cline, S. D., & Coscia, C. J. (1988). Stimulation of sanguinarine production by combined fungal elicitation and hormonal deprivation in cell suspension culture of papaver bracteatum. Plant Physiology, 86, 161–165.PubMedPubMedCentralCrossRefGoogle Scholar
  26. Coffin, P., Sherman, S., & Curtis, M. (2010). Underestimated and overlooked: A global review of drug overdose and overdose prevention. In C. Cook (Ed.), global state of harm reduction: Key issues for broadening the response. London: International Harm Reduction Association.Google Scholar
  27. Courtwright, D. T. (2009). Forces of habit drugs and the making of the modern world (1st ed.pp. 36–37). Cambridge, MA: Harvard University Press.Google Scholar
  28. Dewick, P. M. (2002). Alkaloids. In Medicinal natural products (2nd ed.). New York: Wiley.Google Scholar
  29. Diamond, A., & Penix, I. D. (2016). Metabolic engineering for the production of plant isoquinoline alkaloids. Plant Biotechnology Journal, 7(2), 1319–1328.CrossRefGoogle Scholar
  30. Dinda, A., Gitman, M., & Singhal, P. C. (2005). Immunomodulatory effect of morphine: Therapeutic implications. Expert Opinion on Drug Safety, 4(4), 669–675.PubMedCrossRefGoogle Scholar
  31. Downs, C. G., Christey, M. C., Davies, K. M., King, G. A., Seelye, J. F., Sinclair, B. K., & Stevenson, D. G. (1994). Hairy roots of Brassica napus: II glutamine synthase over expression alters ammonia assimilation and the response to phosphinothricin. Plant Cell Reports, 14, 41–46.PubMedGoogle Scholar
  32. Dzink, J. L., & Socransky, S. S. (1985). Comparative in vitro activity of sanguinarine against oral microbial isolates. Antimicrobial Agents Chemotherapy, 27, 663–665.PubMedCrossRefGoogle Scholar
  33. Facchini, P. J. (2001). Alkaloid biosynthesis in plants: Biochemistry, cell biology, molecular regulation, and metabolic engineering application. Annual Review of Plant Physiology and Plant Molecular Biology, 52, 29–66.PubMedCrossRefGoogle Scholar
  34. Facchini, P. J., & De Luca, V. (1994). Differential and tissue-specific expression of a gene family for tyrosine/DOPA decarboxylase in opium poppy. Journal of Biological Chemistry, 28, 26684–26690.Google Scholar
  35. Facchini, P. J., & Luca, V. D. (2008). Opium poppy and Madagascar periwinkle: Model non-model systems to investigate alkaloid biosynthesis in plants. The Plant Journal, 54(2), 763–784.PubMedCrossRefGoogle Scholar
  36. Facchini, P. J., & Luca, D. V. (1995). Phloem-specific expression of Tyrosine/Dopa Decarboxylase genes and the biosynthesis of isoquinoline alkaloids in opium poppy. Plant Cell, 7(11), 1811–1821.Google Scholar
  37. Facchini, P. J., & Park, S. U. (2003). Developmental and inducible accumulation of gene transcripts involved in alkaloid biosynthesis in opium poppy. Phytochemistry, 64, 177–186.PubMedCrossRefGoogle Scholar
  38. Facchini, P. J., Penzes, C., Johnson, A. G., & Bull, D. (1996a). Molecular characterization of barbering bridge enzyme genes from opium poppy. Plant Physiology, 112, 1669–1677.PubMedPubMedCentralCrossRefGoogle Scholar
  39. Facchini, P. J., Johnson, A. G., Poupart, J., & De Luca, V. (1996b). Uncoupled defense gene expression and antimicrobial alkaloid accumulation in elicited opium poppy cell cultures. Plant Physiology, 111, 687–697.PubMedPubMedCentralCrossRefGoogle Scholar
  40. Fedde, F. (1909). In A. Engler (Ed.), Das Pflanzenfamilien (Vol. 40). Leipzig: Wilhelm Engelmann.Google Scholar
  41. Fisher, G. L. (Ed.). (2009). Encyclopedia of substance abuse prevention treatment & recovery (p. 564). Los Angeles: SAGE.Google Scholar
  42. Flem-Bonhomme, V. L., Laurain-Mattar, D., & Fliniaux, M. A. (2004). Hairy root induction of Papaver somniferum var. album, a difficult-to-transform plant, by A. rhizogenes LBA 9402. Planta, 218, 890–893.Google Scholar
  43. Flores, H. E., & Filner, P. (1985). Metabolic relationships of putrescine, GABA and alkaloids in cell and root cultures of Solanaceae. In K. H. Neumann, W. Barz, & E. Reinhard (Eds.), Primary and secondary metabolism of plant cell cultures (pp. 174–185). Berlin: Springer.CrossRefGoogle Scholar
  44. Flores, H. E., & Medina-Bolivar, F. (1995). Root culture and plant natural products: “Unearthing” the hidden half of plant metabolism. Plant Tissue Culture and Biotechnology, 1, 59–74.Google Scholar
  45. Gerardy, R., & Zenk, M. H. (1993). Formation of salutaridine from (R)-reticuline by a membrane bound cytochrome-P-450 enzyme from Papaver somniferum. Phytochemistry, 32, 79–86.CrossRefGoogle Scholar
  46. Giri, A., & Narasu, M. L. (2000). Transgenic hairy roots: Recent trends and applications. Biotechnology Advances, 18, 1–22.PubMedCrossRefGoogle Scholar
  47. Glare, P. A., & Walsh, T. D. (1991). Clinical pharmacokinetics of morphine. Therapeutic Drug Monitoring, 13(1), 1–23.PubMedCrossRefGoogle Scholar
  48. Gottlieb, O. R., Kaplan, M. A. C., & Zocher, D. H. T. (1993). A chemosystematic overview of Magnoliidae, Ranunculidae, Caryophyllidae and Hamamelididae. In K. Kubitzki, J. G. Rohwer, & V. Bittrich (Eds.), The families and genera of vascular plants (Vol. II). Springer Berlin.Google Scholar
  49. Hagel, J. M., Macleod, B. P., & Facchini, P. J. (2007). Ii.2 opium poppy. In E. C. Pua & M. R. Davey (Eds.), Biotechnology in agriculture and forestry, Transgenic Crops VI (Vol. 61). Heidelberg: Springer.Google Scholar
  50. Hamill, J. D., Parr, A. J., Rhodes, M. J. C., Robins, R. J., & Walton, N. J. (1987). New routes to plant secondary products. BioTechnology, 5, 800–804.Google Scholar
  51. Hamill, J. D., Robins, R. J., Parr, A. J., Evans, P. M., Furze, J. D., & Rhodes, M. J. C. (1990). Over expressing a yeast ornithine de-carboxylase gene in transgenic roots of Nicotiana rustica can lead to enhanced nicotine accumulation. Plant Molecular Biology, 15, 27–38.PubMedCrossRefGoogle Scholar
  52. Hammer, K., & Fritisch, R. (1977). The question of ancestral species of cultivated poppy (P. somniferum L.). Kulture Pflanze, 25, 113.CrossRefGoogle Scholar
  53. Hassel, S. J., & Sawe, J. (1993). Morphine pharmacokinetics and metabolism in humans. Enterohepatic cycling and relative contribution of metabolites to active opioid concentrations. Clinical Pharmacokinectics, 24(4), 344–354.CrossRefGoogle Scholar
  54. Hashimoto, T., Matsuda, J., & Yamada, Y. (1993). Two-step epoxidation of hyoscyamine to scopolamine is catalyzed by bifunctional hyoscyamine 6b-hydroxylase. FEBS Letters, 329, 35–39.Google Scholar
  55. Hirshi, N. J., & Hrishi, K. (1960). Studies on the correlation between male sterility and flower colour in the F2 of an interspecific cross between Papaver setigerum and P. somniferum. Genetica, 31, 410.CrossRefGoogle Scholar
  56. Huang, F. C., & Kutchan, T. M. (2000). Distribution of morphinan and benzophenanthridine alkaloid gene transcript accumulation in Papaver somniferum. Phytochemistry, 53, 555–564.PubMedCrossRefGoogle Scholar
  57. Huffman, G. A., White, F. F., Gordon, M. P., & Nester, E. W. (1984). Hairy root-inducing plasmid: Physical map and homology to tumor inducing plasmids. Journal of Bacteriology, 157, 269–276.PubMedPubMedCentralGoogle Scholar
  58. Husain, A., & Sharma, J. R. (1983). The Opium Poppy (Medicinal and Aromatic Plants Series-I). Lucknow: Central Institute of Medicinal and Aromatic Plants.Google Scholar
  59. Kamei, J. (1996). Role of opioidergic and serotonergic mechanisms in cough and antitussives. Pulmonary Pharmacology, 9(5–6), 349–356.PubMedCrossRefGoogle Scholar
  60. Kamo, K. K., Kimoto, W., Hsu, A. F., Mahlberg, P. G., & Bills, D. D. (1982). Morphinan alkaloids in cultured tissues and redifferentiated organs of Papaver somniferum. Phytochemistry, 21, 219–222.CrossRefGoogle Scholar
  61. Khan, N., Woodruff, T. M., & Smith, M. T. (2014). Establishment and characterization of an optimized mouse model of multiple sclerosis-induced neuropathic pain using behavioral, pharmacologic, histologic and immunohistochemical methods. Pharmacology, Biochemistry, and Behavior, 126, 13–27.PubMedCrossRefGoogle Scholar
  62. Kutchan, T. M., & Zenk, M. H. (1993). Enzymology and molecular biology of benzophenanthridine alkaloid biosynthesis. Journal of Plant Research, 3, 165–173.Google Scholar
  63. Kutchan, T. M., Rush, M. D., & Coscia, C. J. (1986). Subcellular localization of alkaloids and dopamine in different vacuolar compartments of Papaver bracteatum. Plant Physiology, 81, 161–166.PubMedPubMedCentralCrossRefGoogle Scholar
  64. Larkin, P. J., Miller, J. A., Allen, R. S., Chitty, J. A., Gerlach, W. L., Frick, S., Kutchan, T. M., & Fist, A. J. (2007). Increasing morphinan alkaloid production by over-expressing codeinone reductase in transgenic Papaver somniferum. Plant Biotechnology Journal, 5, 26–37.PubMedCrossRefGoogle Scholar
  65. Laurain-Mattar, D., Gillet-Manceau, F., Buchon, L., Nabha, S., Fliniaux, M.-A., & Jacquin-Dubreuil, A. (1999). Somatic embryogenesis and rhizogenesis of tissue cultures of two genotypes of Papaver somniferum: Relationships to alkaloid production. Planta Medica, 65, 167–170.PubMedCrossRefGoogle Scholar
  66. Lesk, A. M. (2000). Introduction to bioinformatics. Oxford: Oxford University Press.Google Scholar
  67. Liu, J. K., & Couldwell, W. T. (2005). Intra-arterial papaverine infusions for the treatment of cerebral vasospasm induced by aneurysmal subarachnoid hemorrhage. Neurocritical Care, 2(2), 124–132.PubMedCrossRefGoogle Scholar
  68. Lodhi, A. H., Bongaerts, R. J. M., Verpoorte, R., Coomber, S. A., & Charlwood, B. V. (1996). Expression of bacterial isochoris-mate synthase (E C in transgenic root cultures of Rubia peregrina. Plant Cell Reports, 16, 54–57.PubMedCrossRefGoogle Scholar
  69. McCarthy, L. M., Wetzel, J. K. S., Eisenstein, T. K., & Rogers, T. J. (2001). Opioids, opioid receptors, and the immune response. Drug and Alcohol Dependence, 62, 111–123.PubMedCrossRefGoogle Scholar
  70. Meijerink, W. J. H. J., Molina, P. E., & Abumrad, N. N. (1999). Mammalian opiate alkaloid synthesis: Lessons derived from plant biochemistry. Shock, 12(3), 165–173.PubMedCrossRefGoogle Scholar
  71. Merck, G. (1848). Vorläufige Notiz über eine neue organische base im opium [Preliminary notice of a new organic base in opium]. Annalen der Chemie und Pharmacie, 66, 125–128.CrossRefGoogle Scholar
  72. Ming, H., Jiang, L., Ren, Z., Wang, G., & Wang, J. (2016). Noscapine targets EGFRp-Tyr1068 to suppress the proliferation and invasion of MG63 cells. Scientific Reports, 6.
  73. Nader, B. L., Taketa, A. T., Pereda-Miranda, R., & Villarreal, M. L. (2006). Production of triterpenoids in liquid-cultivated hairy roots of Galphimia glauca. Planta Medica, 72, 842–844.PubMedCrossRefGoogle Scholar
  74. Narcotic Drugs. (2014). International Narcotics Control Board. 2015 pp. 21, 30. ISBN: 9789210481571.
  75. Neligan, A. R. (1927). The opium question. London: Bale and Curnow.Google Scholar
  76. Nergiz, C., & Oltes, S. (1994). The proximate composition and some minor constituents of poppy seeds. Journal of the Science of Food and Agriculture, 66, 117–120.CrossRefGoogle Scholar
  77. Nessler, C. L., Allen, R. D., & Galewsky, S. (1985). Identification and characterization of latex-specific proteins in opium poppy. Plant Physiology, 79, 499–504.PubMedPubMedCentralCrossRefGoogle Scholar
  78. Ohlsson, S., Holm, L., Myrberg, O., Sundström, A., & Yue, Q. Y. (2008). Noscapine may increase the effect of warfarin. British Journal of Clinical Pharmacology, 65(2), 277–278.PubMedCrossRefGoogle Scholar
  79. Oksman-Caldentey, & Arroo, R. (2000). Regulation of tropane alkaloid metabolism in plants and plant cell cultures. In R. Verpoorte & A. W. Alfermann (Eds.), Metabolic engineering of plant secondary metabolism (pp. 253–281). Dordrecht: Kluwer Academic Press.CrossRefGoogle Scholar
  80. Page, G. G., Ben-Eliyahu, S., & Yirmiya, R. (1993). Morphine attenuates surgery-induced enhancement of metastatic colonization in rats. Pain, 54(1), 21–28.PubMedCrossRefGoogle Scholar
  81. Park, S. U., & Facchini, P. J. (2000a). Agrobacterium rhizogenes-mediated transformation of opium poppy, Papaver somniferum L., and California poppy, Eschscholzia californica Cham., root cultures. Journal of Experimental Biology, 51, 1005–1016.Google Scholar
  82. Park, S. U., & Facchini, P. J. (2000b). Agrobacterium-mediated genetic transformation of California poppy, Eschscholzia californica Cham., via somatic embryogenesis. Plant Cell Reports, 19, 421–426.Google Scholar
  83. Park, S. U., Yu, M., & Facchini, P. J. (2003). Modulation of berberine bridge enzyme levels in transgenic root cultures of California poppy alters the accumulation of benzophenanthridine alkaloids. Plant Molecular Biology, 51, 153–164.PubMedCrossRefGoogle Scholar
  84. Phillipson, J. D. (1983). Lntraspecific variation and alkaloids of Papaver species. Planta Medica, 48, 187–192.PubMedCrossRefGoogle Scholar
  85. Poser, C. M. (1974). Letter: Papaverine in prophylactic treatment of migraine. Lancet, 1(7869), 1209–1222.Google Scholar
  86. Preininger, V. (1985). Chemotaxonomy of the Papaveraceae alkaloids. In J. D. Phillipson, M. F. Roberts, & M. H. Zenk (Eds.), The chemistry and biology of isoquinoline alkaloids (pp. 23–37). Berlin: Springer.CrossRefGoogle Scholar
  87. Rhodes, M. J. C., Robins, R. J., Hamill, J. D., Parr, A. J., Hilton, M. G., & Walton, N. J. (1990). Properties of transformed root cultures. In B. V. Charlwood, & M. J. C. Rhodes (Eds.), Secondary products from plant tissue culture (Proceedings of the Phytochemical Society of Europe, pp. 201–225). Oxford: Clarendon Press.Google Scholar
  88. Roberts, M. F. (1988). lsoquinolines (papaver alkaloids). In F. Constabel & I. K. Vasil (Eds.), Cell culture and somatic cell genetics of plants (Vol. 5, pp. 315–334). New York: Academic.Google Scholar
  89. Roberts, M. F., Carthy, D. M., Kutchan, T. M., & Coscia, C. J. (1983). Localization of enzymes and alkaloidal metabolites in Papaver latex. Archives of Biochemistry and Biophysics, 222, 599–609.PubMedCrossRefGoogle Scholar
  90. Rutherfold, R. M., Azher, T., & Gilmartin, J. J. (2002). Dramatic response to nebulized morphine in an asthmatic patient with severe chronic cough. Irish Medical Journal, 95(4), 113–114.Google Scholar
  91. Schroeder, K., & Fahey, T. (2004). Over-the-counter medications for acute cough in children and adults in ambulatory settings. Cochrane Database of Systematic Reviews, 4, CD001831.Google Scholar
  92. Schuchmann, R., & Wellmann, E. (1983). Somatic embryogenesis of tissue of Papaver somniferum and Papaver orientale and its relationship to alkaloid and lipid metabolism. Plant Cell Reports, 2, 88–91.PubMedCrossRefGoogle Scholar
  93. Schumacher, H. (1983). Alkaloid biosynthesis. Planta Medica, 48, 212–222.PubMedCrossRefGoogle Scholar
  94. Schumacher, H. M., Gundlach, H., Fiedler, F., & Zenk, M. H. (1987). Elicitation of benzophenanthridine alkaloid synthesis in Eschscholtzia cell cultures. Plant Cell Reports, 6, 410–413.PubMedGoogle Scholar
  95. Seifert, F., Todorov, D. K., Hutter, K. J., & Zeller, W. J. (1996). Cell cycle effects of thaliblastine. Journal of Cancer Research and Clinical Oncology, 122, 707–710.PubMedCrossRefGoogle Scholar
  96. Sevon, N., & Oksman-Caldentey, K. M. (2002). Agrobacterium rhizogenes-mediated transformation: Root cultures as a source of alkaloids. Planta Medica, 68, 859–868.PubMedCrossRefGoogle Scholar
  97. Sharafi, A., Sohi, H. H., Mousavi, A., Azadi, P., & Khalifani Razavi, B. H. K. (2013a). Metabolic engineering of morphinan alkaloids by over-expression of codeinone reductase in transgenic hairy roots of Papaver bracteatum, the Iranian poppy. Biotechnology Letters, 35, 445–453.PubMedCrossRefGoogle Scholar
  98. Sharafi, A., Mousavi, A., Sohi, H. H., Azadi, P., Dehsara, B., & Khalifani, B. H. (2013b). Enhanced morphinan alkaloid production in hairy root cultures of Papaver bracteatum by over-expression of salutaridinol 7-o-acetyltransferase gene via Agrobacterium rhizogenes mediated transformation. World Journal of Microbiology, 29(11), 2125–2131.CrossRefGoogle Scholar
  99. Sharma, P. V. (1973). Drugs and landmarks of the history of Indian medicine. Journal of Research in Indian medicine, 8(4), 86.Google Scholar
  100. Sharma, D. (1980). Pollen morphology of two cultivars of P. somniferum L. Current Science, 49, 710.Google Scholar
  101. Sharma, J. R., & Singh, O. P. (1983). Genetics and genetic improvement. In A. Husain & J. R. Sharma (Eds.), The Opium Poppy (pp. 39–68). Lucknow: Central Institute of Medicinal and Aromatic Plants.Google Scholar
  102. Shukla, S., & Singh, S. P. (2003). Exploitation of inter-specific crosses and its prospects for developing novel plant type in opium poppy (Papaver somniferum L.). In P. C. Trivedi (Ed.), Herbal drugs and biotechnology (pp. 210–239). Jaipur: Pointer Publisher.Google Scholar
  103. Sillanpää, M., & Koponen, M. (1978). Papaverine in the prophylaxis of migraine and other vascular headache in children. Acta Paediatrica Scandinavica, 67(2), 209–212.PubMedCrossRefGoogle Scholar
  104. Singh, H. P., Singh, S. P., Singh, A. K., & Patra, N. K. (1999). The component of genetic variances in biparental progenies of opium poppy (Papaver somniferum). Journal of Medicine in Aromatic Plant Science, 21, 724–726.Google Scholar
  105. Singh, H., Singh, P., Kumari, K., Chandra, A., Dass, S. K., & Chandra, R. (2013). A review on noscapine, and its impact on heme metabolism. Current Drug Metabolism, 14(3), 351–360.PubMedCrossRefGoogle Scholar
  106. Slightom, J. L., Durand-Tardif, M., Jouanin, L., & Tepfer, D. (1986). Nucleotide sequence analysis of TL-DNA of agrobacterium rhizogenes agropine type plasmid. The Journal of Biological Chemistry, 261, 108–121.PubMedGoogle Scholar
  107. Susanne, F., Julie, A. C., Robert, K., Jürgen, S., Robert, S. A., Philip, J. L., & Toni, M. K. (2004). Transformation of opium poppy (Papaver somniferumL.) with antisense berberine bridge enzyme gene (anti-bbe) via somatic embryogenesis results in an altered ratio of alkaloids in latex but not in roots. Transgenic Research, 13(6), 607–613.Google Scholar
  108. Takeuchi, K., Sakamoto, S., Nagayoshi, Y., Nishizawa, H., & Matsubara, J. (2004). Reactivity of the human internal thoracic artery to vasodilators in coronary artery bypass grafting. European Journal of Cardio-Thoracic Surgery, 26(5), 956–959.PubMedCrossRefGoogle Scholar
  109. Tepfer, M., & Casse-Delbart, F. (1987). Agrobacterium rhizogenes as a vector for transforming higher plants. Microbiological Sciences, 4, 24–28.PubMedGoogle Scholar
  110. Tetenyi, P. (1997). Opium poppy (Papaver somniferum): Botany and horticulture. In Jules & Janick (Eds.), Horticultural reviews (Vol. 19, pp. 373–408).Google Scholar
  111. Tiwari, R. K., Trivedi, M., Guang, Z. C., Guo, G. Q., & Zheng, G. C. (2007). Genetic transformation of Gentiana macrophylla with agrobacterium rhizogenes: Growth and production of secoiridoid glucoside gentiopicroside in transformed hairy root cultures. Plant Cell Reports, 26, 199–210.PubMedCrossRefGoogle Scholar
  112. Tiwari, R. K., Trivedi, M., Guang, Z. C., Guo, G. Q., & Zheng, G. C. (2008). Agrobacterium rhizogenes mediated transformation of Scutellaria baicalensis and production of flavonoids in hairy roots. Biologia Plantarum, 52(1), 26–35.CrossRefGoogle Scholar
  113. Trease, G., & Evans, W. C. (1972). Pharmacognosy (10th ed.). London: Bailliere Tindall.Google Scholar
  114. Tshibangu, J. N., Wright, A. D., & Konig, G. M. (2003). HPLC isolation of the anti-plasmodially active bisbenzylisoquinone alkaloids present in roots of Cissampelos mucronata. Phytochemical Analysis, 14, 13–22.PubMedCrossRefGoogle Scholar
  115. Veslovskaya, M. A. (1976). The poppy. New Delhi/New York: American Publishing Co., (translated from Russian).Google Scholar
  116. Vijayan, N. (1977). Brief therapeutic report: Papaverine prophylaxis of complicated migraine. Headache, 17(4), 159–162.PubMedCrossRefGoogle Scholar
  117. Walsh, T. D. (1984). Oral morphine in chronic cancer pain. Pain, 18(1), 1–11.PubMedCrossRefGoogle Scholar
  118. Warner, M., Trinidad, J. P., Bastian, B. A., Minino, A. M., & Hedegaard, H. (2016). Drugs most frequently involved in drug overdose deaths: United States, 2010-2014. National Vital Statistics Reports, 65(10), 1–15.PubMedGoogle Scholar
  119. Weber, T., & Kim, H. U. (2016). The secondary metabolite bioinformatics portal: Computational tools to facilitate synthetic biology of secondary metabolite production. Synthetic and Systems Biology, 1(2), 69–79.CrossRefGoogle Scholar
  120. White, P. T., & Raymer, S. (1985, February). The poppy. Natural Geography, 143–189.Google Scholar
  121. White, F. F., Taylor, B. H., Huffman, G. A., Gordon, M. P., & Nester, E. W. (1985). Molecular and genetic analysis of the transferred DNA regions of the root-inducing plasmid of agrobacterium rhizogenes. Journal of Bacteriology, 164, 33–44.PubMedPubMedCentralGoogle Scholar
  122. WHO. (1996). Cancer pain relief: With a guide to opioid availability (2nd ed.). Geneva: World Health Organization.Google Scholar
  123. WHO Model List of Essential Medicines (19th List). (2015, April). World Health Organization.
  124. Yadav, H. K., Shukla, S., & Singh, S. P. (2006). Genetic variability and interrelationship among opium and its alkaloids in opium poppy (Papaver somniferum L.). Euphytica, 150, 207–214.CrossRefGoogle Scholar
  125. Ye, K., Ke, Y., Keshava, N., Shanks, J., Kapp, J. A., Tekmal, R. R., Petros, J., & Joshi, H. C. (1998). Opium alkaloid noscapine is an antitumor agent that arrests metaphase and induces apoptosis in dividing cells. Proceedings of the National Academy of Sciences of the United States of America, 95, 1601–1606.PubMedPubMedCentralCrossRefGoogle Scholar
  126. Yoshikawa, T., & Furuya, T. (1985). Morphinan alkaloid production by tissue cultures differentiated from cultured cells of Papaver somniferum. Planta Medica, 2, 110–113.CrossRefGoogle Scholar
  127. Yoshimatsu, K., & Shimomura, K. (1992). Transformation of opium poppy (Papaver somniferum L.) with agrobacterium rhizogenes MAFF 03-01724. Plant Cell Reports, 11, 132–136.PubMedCrossRefGoogle Scholar
  128. Yun, D. J., Hashimoto, T., & Yamada, Y. (1992). Metabolic engineering of medicinal plants: transgenic Atropa belladonna with an improved alkaloid composition. Proceedings of the National Academy of Sciences of the United States of America, 89, 11799–11803.PubMedPubMedCentralCrossRefGoogle Scholar
  129. Zenk, M. H. (1985). Enzymology of benzylisoquinoline alkaloid formation. In J. D. Phillipson, M. F. Roberts, & M. H. Zenk (Eds.), The chemistry and biology of lsoquinoline alkaloids (pp. 240–256). Berlin: Springer.CrossRefGoogle Scholar
  130. Zenk, M. H., & Juenger, M. (2007). Evolution and current status of the phytochemistry of nitrogenous compounds. Phytochemistry, 68, 2757–2772.PubMedCrossRefGoogle Scholar
  131. Ziegler, J. R., & Facchini, P. J. (2008). Alkaloid biosynthesis: Metabolism and trafficking. Annual Review of Plant Biology, 59, 735–769.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Mala Trivedi
    • 1
  • Aditi Singh
    • 1
  • Parul Johri
    • 1
  • Rachana Singh
    • 1
  • Rajesh K. Tiwari
    • 1
    Email author
  1. 1.Amity Institute of Biotechnology, Amity University Uttar PradeshLucknow CampusIndia

Personalised recommendations