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Biotechnological approaches for the production of forskolin, withanolides, colchicine and tylophorine

Published online by Cambridge University Press:  12 February 2007

Sumita Jha ,
Maumita Bandyopadhyay ,
Kuntal Narayan Chaudhuri ,
Seemanti Ghosh  and
Biswajit Ghosh
Sumita Jha*
Affiliation:
Centre of Advanced Study in Cell and Chromosome Research, Department of Botany, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, -700 019, India
Maumita Bandyopadhyay
Affiliation:
Centre of Advanced Study in Cell and Chromosome Research, Department of Botany, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, -700 019, India
Kuntal Narayan Chaudhuri
Affiliation:
Centre of Advanced Study in Cell and Chromosome Research, Department of Botany, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, -700 019, India
Seemanti Ghosh
Affiliation:
Centre of Advanced Study in Cell and Chromosome Research, Department of Botany, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, -700 019, India
Biswajit Ghosh
Affiliation:
Centre of Advanced Study in Cell and Chromosome Research, Department of Botany, University of Calcutta, 35, Ballygunge Circular Road, Kolkata, -700 019, India
*
*Corresponding author: E-mail: [email protected] or [email protected]
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Abstract

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Keywords

colchicineforskolinhairy rootssecondary metabolitesshooty teratomastissue culturetransformed culturestylophorinewithanolides
Type
Research Article
Information
Plant Genetic Resources , Volume 3 , Issue 2 , August 2005 , pp. 101 - 115
Copyright
Copyright © NIAB 2005

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References

Abe, F, Iwase, Y, Yamauchi, T, Honda, K and Hayashi, N (1995) Phenanthroindolizidine alkaloids from Tylophora tanakae. Phytochemistry 39: 695–699.CrossRefGoogle Scholar
Abe, F, Yamauchi, T, Honda, K, Omura, H and Hayashi, N (2001) Sequestration of phenanthro-indolizidine alkaloids by an Asclepiadaceae-feeding danaid butterfly, Ideopsis similis. Phytochemistry 56: 697–701.CrossRefGoogle ScholarPubMed
Ammon, HPT and Müller, AB (1985) Forskolin: from Ayruvedic remedy to a modern agent. Planta Medica 51: 473–477.CrossRefGoogle Scholar
Andreu, JM, Perez-Ramirez, B, Gorbunoff, MJ, Ayala, D and Timasheff, SN (1998) The role of the colchicine ring A and its methoxy groups in the binding to tubulin and microtubule inhibition. Biochemistry 37: 8356–8368.CrossRefGoogle Scholar
Anonymous (1956) The Wealth of India (Raw Materials) IV. New Delhi: CSIR, 139Google Scholar
Anonymous (1976) The Wealth of India (Raw Materials) X. New Delhi: CSIR, 398–400., 582–585Google Scholar
Anonymous (2004) Withania somnifera —monograph. Alternative Medicine Review 9: 211–214.Google Scholar
Bellet, P and Gaignault, JC (1985) Le Gloriosa superba L. et la production de substances colchiciniques. Annales Pharmaceutiques Françaises 43: 345–347.Google Scholar
Benzamine, BD and Mulchandani, NB (1973) Studies in biosynthesis of secondary constituents in tissue cultures of Tylophora indica. Planta Medica 23: 394–397.Google Scholar
Benzamine, BD and Mulchandani, NB (1976) Effect of gamma irradiation on biosynthetic potential of callus cultures of Tylophora indica. Planta Medica 29: 37–40.Google Scholar
Benzamine, BD, Heble, MR and Chadha, MS (1979) Alkaloid synthesis in tissue culture and regenerated plants of Tylophora indica Merr. (Asclepiadaceae). Zeitschrift für Pflanzenphysiologie 92: 77–84.Google Scholar
Berlin, J, Martin, B, Nowak, J, Witte, L, Wray, L and Strack, D (1989) Effects of permeabilization on the biotransformation of phenylalanine by immobilized tobacco cell cultures. Zeitschrift für Naturforsch 44: 249–254.CrossRefGoogle Scholar
Bhattacharyya, R and Bhattacharya, S (2001) In vitro multiplication of Coleus forskohlii Briq.: an approach towards shortening the protocol. In Vitro Cellular & Developmental Biology—Plant 37: 572–575.CrossRefGoogle Scholar
Bhutani, KK, Sharma, GL, Sarin, AN, Kaur, R, Kumar, V and Atal, CK (1985) In vitro amoebicidal and bactericidal activities in medicinal plants. Indian of Pharmaceutical Sciences 47: 65–67.Google Scholar
Bourgaud, F, Gravot, A, Milesi, S and Gontier, E (2001) Production of plant secondary metabolites: a historical perspective. Plant Science 161: 839–851.CrossRefGoogle Scholar
Chaudhuri, KN, Ghosh, B and Jha, S (2004) The root: a potential new source of competent cells for high-frequency regeneration in Tylophora indica. Plant Cell Reports 22: 731–740.Google Scholar
Chaudhuri, KN, Ghosh, B, Tepfer, D and Jha, S (2005) Genetic transformation of Tylophora indica with Agrobacterium rhizogenes A4: growth and tylophorine productivity in different transformed root clones. Plant Cell Reports 24: 25–35.CrossRefGoogle ScholarPubMed
Chopra, RN, Chopra, IC, Handa, KL and Kapur, LD (1958) Indigenous Drugs of India. Calcutta: UN Dhur & SonsGoogle Scholar
Clewer, HWB, Green, SJ and Tutin, F (1915) The constituents of Gloriosa superba. Journal of the Chemical Society 107: 835–846.CrossRefGoogle Scholar
Donaldson, GR, Atkinson, MR and Murray, AW (1968) Inhibition of protein synthesis in Ehrlich ascites -tumor cells by the phenanthrene alkaloids tylophorine, tylocrebrine and cryptopleurine. Biochemical and Biophysical Research Communications 31: 104–109.CrossRefGoogle ScholarPubMed
Dymock, W, Warden, CJH and Hooper, D (1891) Pharmacographia Indica: A History of Principal Drugs of Vegetable Origin Met with British India, Vol 2. Dehra Dun: Bishen Singh Mahendra Pal SinghGoogle Scholar
Engprasert, S, Taura, F, Makoto, M and Shoyama, Y (2004) Molecular cloning and functional expression of geranylgeranyl pyrophosphate synthase from Coleus forskohlii Briq. BMC Plant Biology 4: 18CrossRefGoogle ScholarPubMed
Faisal, M and Anis, M (2003) Rapid mass propagation of Tylophora indica Merrill via leaf callus culture. Plant Cell, Tissue and Organ Culture 75: 125–129.CrossRefGoogle Scholar
Finnie, JF, Van Staden, J (1991) Isolation of colchicine from Sandersonia aurantiaca and Gloriosa superba. Variation in alkaloid levels of plants grown in vivo. Journal of Plant Physiology 138: 691–695.CrossRefGoogle Scholar
Finnie, JF and Van Staden, J (1994) Gloriosa superba L. (Flame lily): micropropagation and in vitro production of colchicine. In: Bajaj, YPS (ed.) Biotechnology in Agriculture and Forestry, Vol. 26. Medicinal and Aromatic Plants VI Berlin: Springer-Verlag, 146–166.Google Scholar
Furmanowa, M, Gajdzis-Kuls, D, Ruszkowska, J, Czarnocki, Z, Obidoska, G, Sadowska, A, Rani, R and Upadhyay, SN (2001) In vitro propagation of Withania somnifera and isolation of withanolides with immunosuppressive activity. Planta Medica 67: 146–149.CrossRefGoogle ScholarPubMed
Gellert, E (1982) The indolizidine alkaloids. Journal of Natural Products 45: 50–73.CrossRefGoogle Scholar
Gellert, E and Rudzats, R (1964) The antileukemia activity of tylocrebrine. Journal of Medicinal Chemistry 7: 361–362.CrossRefGoogle ScholarPubMed
Gellert, E, Govindachhari, TR, Lakshmikantham, MV, Ragade, IS, Rudzats, R and Viswanathan, N (1962) The alkaloids of Tylophora crebriflora: structure and synthesis of tylocrebrine, a new phenanthroindolizidine alkaloid. Journal of the Chemical Society 1008–1014.Google Scholar
Ghosh, B, Mukherjee, S, Jha, TB and Jha, S (2002) Enhanced colchicine production in root cultures of Gloriosa superba by direct and indirect precursors of the biosynthetic pathway. Biotechnology Letters 24: 231–234.CrossRefGoogle Scholar
Ghosh, S and Jha, S (2005) Colchicine accumulation in in vitro cultures of Gloriosa superba. In: D', , Souza, L, Anuradha, M, Nivas, S, Hegde, S and Rajendra, K (eds) Biotechnology for a Better Future. Mangalore: SAC Publications, 92–98.Google Scholar
Gopalakrishnan, C, Shankaranarayan, D, Kameswaran, L and Natarajan, S (1979) Pharmacological investigations of tylophorine, the major alkaloid of Tylophora indica. Indian Journal of Medical Research 69: 513–520.Google ScholarPubMed
Govindachari, TR, Pai, BR and Nagarajan, K (1954) Chemical examination of Tylophora asthmatica Part I. Journal of the Chemical Society 5192: 2801Google Scholar
Govindachari, TR, Lakshmikantham, MV and Rajadurai, S (1961) Chemical examination of Tylophora asthmatica —V. Structure of tylophorinine. Tetrahedron 14: 284–295.CrossRefGoogle Scholar
Hadacek, F (2002) Secondary metabolites as plant traits: current assessment and future perspectives. CRC Critical Reviews in Plant Science 21: 273–322.Google Scholar
Hansen, G and Wright, MS (1999) Recent advances in the transformation of plants. Trends in Plant Science 4: 226–231.CrossRefGoogle ScholarPubMed
Hayashi, T, Yoshida, K and Sano, K (1988) Formation of alkaloids in suspension cultured Colchicum autumnale. Phytochemistry 27: 1371–1374.Google Scholar
Herbert, RB and Knagg, E (1986) The biosynthesis of phenethylisoquinoline alkaloid, colchicine from cinnamaldehyde and dihydrocinnamaldehyde. Tetrahedron Letters 27: 1099–1102.CrossRefGoogle Scholar
Hooykaas, PJJ and Beijersbergen, AGM (1994) The virulence system of Agrobacterium tumefaciens. Annual Review of Phytopathology 32: 157–179.CrossRefGoogle Scholar
Jayanthi, M and Mandal, PK (2001) Plant regeneration through somatic embryogenesis and RAPD analysis of regenerated plantlets in Tylophora indica (Burm. f.) Merrill. In Vitro Cellular & Developmental Biology—Plant 37: 576–580.CrossRefGoogle Scholar
Jha, S (1997) Genetic transformation for production of secondary metabolites. In: Ramawat, KG and Merillon, JM (eds) Biotechnology: Secondary Metabolites. New Delhi: Oxford & IBH Publishing Co, 305–329.Google Scholar
Karnick, CR (1975) Phytochemical investigations of some Tylophora species found in India. Planta Medica 27: 333–336.Google Scholar
Krause, J (1986) Production of Gloriosa tubers from seeds. Acta Hortica 177: 353–360.Google Scholar
Krombholz, R, Mersinger, R, Kreis, W and Reinhard, E (1992) Production of forskolin by axenic Coleus forskohlii roots cultivated in shake flasks and 20-l glass jar bioreactors. Planta Medica 58: 328–333.CrossRefGoogle ScholarPubMed
Kulkarni, AA, Thengane, SR and Krishnamurthy, KV (1996) Direct in vitro regeneration of leaf explants of Withania somnifera (L) Dunal. Plant Science 119: 163–168.Google Scholar
Laird, SA (1999) The botanical medicine industry. In: Kate, K and Laird, SAThe Commercial Use of Biodiversity: Access to Genetic Resources and Benefit-sharing. London: Earthscan, 78–116.Google Scholar
Lambert, J, Srivastava, J and Vietmeyer, N (1997) Medicinal Plants: Rescuing a Global Heritage. World Bank Technical Paper 355. Washington, DC: World BankCrossRefGoogle Scholar
Lavie, D, Glotter, E and Shvo, Y (1965) Constituents of Withania somnifera Dun: the structure of withaferin A. Journal of the Chemical Society 7517Google Scholar
Manickam, VS, Elango Mathavan, R and Antonisamy, R (2000) Regeneration of Indian ginseng plantlets from stem callus. Plant Cell, Tissue and Organ Culture 62: 181–185.Google Scholar
Manjula, S, Job, A and Nair, GM (2000) Somatic embryogenesis from leaf derived callus of Tylophora indica (Burm. f.) Merrill. Indian Journal of Experimental Biology 38: 1069–1072.Google Scholar
Marone, G, Columbo, M, Triggiani, M, Vigorita, S and Formisano, S (1986) Forskolin inhibits the release of histamine from human basophils and mast cells. Agents Actions 18: 96–99.Google Scholar
Mersinger, R, Dornauer, H and Reinhard, E (1988) Formation of forskolin by suspension cultures of Coleus forskohlii. Planta Medica 54: 200–204.CrossRefGoogle ScholarPubMed
Mhatre, M, Bapat, VA and Rao, PS (1984) Plant regeneration in protoplast cultures of Tylophora indica. Journal of Plant Physiology 115: 231–235.CrossRefGoogle ScholarPubMed
Moldenhauer, D, Fuerst, B, Diettrich, B and Luckner, M (1990) Cardenolides in Digitalis lanata cells transformed with Ti-plamids. Planta Medica 56: 435–438.CrossRefGoogle Scholar
Mukherjee, S, Ghosh, B and Jha, S (1996) Forskolin synthesis in in vitro culture of Coleus forskohlii Briq. transformed with Agrobacterium tumefaciens. Plant Cell Reports 15: 691–694.CrossRefGoogle ScholarPubMed
Mukherjee, S, Ghosh, B and Jha, S (2000 a) Establishment of forskolin yielding transformed cell suspension cultures of Coleus forskohlii as controlled by different factors. Journal of Biotechnology 76: 73–81.Google Scholar
Mukherjee, S, Ghosh, B and Jha, S (2000 b) Enhanced forskolin production in genetically transformed cultures of Coleus forskohlii by casein hydrolysate and studies on growth and organisation. Biotechnology Letters 22: 133–136.CrossRefGoogle Scholar
Mukherjee, S, Ghosh, B and Jha, S (2003) Higher production of forskolin in genetically transformed cultures of Coleus forskohlii Briq. induced by growth regulators. Journal of Plant Biochemistry and Biotechnology 12: 81–85.CrossRefGoogle Scholar
Mulchandani, NB and Venkatachalam, SR (1976) Alkaloids of Pergularia pallida. Phytochemistry 15: 1561–1563.Google Scholar
Murashige, T and Skoog, F (1962) A revised medium for rapid growth and bioassays with tobacco tissue cultures. Physiologia Plantarum 15: 473–497.CrossRefGoogle Scholar
Nacci, V, Stefancich, G, Giuliano, R, Filachoni, G, Artico, M, Dolfini, E and Morasca, L (1973) [Research on substances with antineoplastic activity. LII. Tylophorine analogs. I. Synthesis and cytostatic and cytotoxic activity of 4-(3,4-dimethoxyphenyl) piperidine derivatives.] Farmaco-Edizione Scientifica 28: 399–410. [in Italian].Google Scholar
Nadkarni, AK (1954) Indian Materia Medica, Vol. 1. Bombay: Popular PrakashanGoogle Scholar
Okuda, H, Morimoto, C and Tsujita, T (1992) Relationship between cyclic AMP production and lipolysis induced by forskolin in rat fat cells. Journal of Lipid Research 33: 225–231.Google Scholar
Pailer, M and Streicher, W (1965) Alkaloids from Vincetoxicum officinale. Monatschefth für Chemie 96: 1094–1102.Google Scholar
Payne, J, Hamill, JD, Robins, RJ and Rhodes, MJC (1987) Production of hyoscyamine by ‘hairy root’ cultures of Datura stramonium. Planta Medica 53: 474–478.CrossRefGoogle ScholarPubMed
Petersen, M (1994) Coleus spp.: in vitro culture and the production of forskolin and rosmarinic acid. In: Bajaj, YPS (ed.) Biotechnology in Agriculture and Forestry, Vol. 26. Medicinal and Aromatic Plants VI Berlin: Springer-Verlag, 69–92.Google Scholar
Ramachandra Rao, S and Ravishankar, GA (2002) Plant cell cultures: chemical factories of secondary metabolites. Biotechnology Advances 20: 101–153.Google Scholar
Rani, G and Grover, IS (1999) In vitro callus induction and regeneration studies in Withania somnifera. Plant Cell, Tissue and Organ Culture 57: 23–27.CrossRefGoogle Scholar
Rani, G, Virk, GS and Nagpal, A (2003) Callus induction and plantlet regeneration in Withania somnifera (L.) Dunal. In Vitro Cellular & Developmental Biology—Plant 39: 468–474.Google Scholar
Rao, KN and Venkatachalam, SR (2000) Inhibition of dihydrofolate reductase and cell growth activity by the phenanthroindolizidine alkaloids pergularinine and tylophorinidine: the in vitro cytotoxicity of these plant alkaloids and their potential as antimicrobial and anticancer agents. Toxicology in Vitro 14: 53–59.Google Scholar
Rao, KN, Bhattacharyya, RK and Venkatachalam, SR (1997) Inhibition of thymidylate synthase and cell growth by the phenanthroindolizidine alkaloids pergularinine and tylophorinidine. Chemico-Biological Interactions 106: 201–211.Google Scholar
Rao, KN, Bhattacharyya, RK and Venkatachalam, SR (1998) Thymidylate synthase activity in leukocytes from patients with chronic myelocytic leukemia and acute lymphocytic leukemia and its inhibition by phenanthroindolizidine alkaloids pergularinine and tylophorinidine. Cancer Letters 128: 183–188.Google Scholar
Rao, KN, Bhattacharyya, RK and Venkatachalam, SR (1999) Inhibition of thymidylate synthase by pergularinine, tylophorinidine and deoxytubulosine. Indian Journal of Biochemistry and Biophysics 36: 442–448.Google Scholar
Rao, KV, Wilson, RA and Cummings, B (1971) Alkaloids of Tylophora indica and T. dalzelli. Journal of Pharmaceutical Sciences 60: 1725–1726.Google Scholar
Rao, PS and Narayanaswamy, S (1972) Morphogenetic investigations in callus cultures of Tylophora indica. Physiologia Plantarum 27: 271–276.Google Scholar
Rao, PS, Narayanaswamy, S and Benjamin, BD (1970) Differentiation ex ovulo of embryos and plantlets in stem tissue cultures of Tylophora indica. Physiologia Plantarum 23: 140–144.Google Scholar
Ray, AB and Gupta, M (1994) Withasteroids, a growing group of naturally occurring steroidal lactones. In: Herz, W, Kirby, GW, Moore, RE, Steglich, W and Tamm, Ch (eds) Progress in the Chemistry of Organic Natural Products Vol. 63. Berlin: Springer-Verlag, 1–106.Google Scholar
Ray, S (2000) Tissue culture and Agrobacterium mediated transformation in Withania somnifera for production of secondary metabolites. PhD Thesis, University of CalcuttaGoogle Scholar
Ray, S and Jha, S (1999) Withanolide synthesis in cultures of Withania somnifera transformed with Agrobacterium tumefaciens. Plant Science 146: 1–7.CrossRefGoogle Scholar
Ray, S and Jha, S (2001) Production of withaferin A in shoot cultures of Withania somnifera. Planta Medica 67: 432–436.CrossRefGoogle ScholarPubMed
Ray, S and Jha, S (2002) Regeneration of Withania somnifera plants. Journal of Tropical Medicinal Plants 3: 89–95.Google Scholar
Ray, S, Ghosh, B, Sen, S and Jha, S (1996) Withanolide production by root cultures of Withania somnifera transformed with Agrobacterium rhizogenes. Planta Medica 62: 571–573.CrossRefGoogle ScholarPubMed
Roja, G, Heble, MR and Sipahamalani, AT (1991) Tissue cultures of Withania somnifera: morphogenesis and withanolide synthesis. Phytotherapy Research 5: 185–187.Google Scholar
Sajc, L, Grubisci, D, Vunjak-Novakovic, G (2000) Bioreactors for plant engineering: an outlook for further research. Biochemical Engineering Journal 4: 89–99.Google Scholar
Saksena, A, Green, MJ, Shue, HJ and Wong, JK (1985) Identity of coleonol with forskolin: structure revision of a base-catalysed rearrangement product. Tetrahedron Letters 26: 551–554.CrossRefGoogle Scholar
Samarajeewa, PK, Dassanayake, MD and Jayaawardena, SDG (1993) Clonal propagation of Gloriosa superba L. Indian Journal of Experimental Biology 31: 719–720.Google Scholar
Sasaki, K, Udagawa, A, Ishimaru, H, Hayashi, T, Alfermann, AW, Nakanishi, F and Shimomura, K (1998) High forskolin production in hairy roots of Coleus forskohlii. Plant Cell Reports 17: 457–459.Google Scholar
Sen, J and Sharma, AK (1991 a) In vitro propagation of Coleus forskohlii Briq. for forskolin synthesis. Plant Cell Reports 9: 696–698.Google Scholar
Sen, J and Sharma, AK (1991 b) Micropropagation of Withania somnifera from germinating seeds and shoot tips. Plant Cell, Tissue and Organ Culture 26: 71–73.CrossRefGoogle Scholar
Sen, J, Sharma, AK, Sahu, NP and Mahato, SB (1992) Production of forskolin in in vitro cultures of Coleus forskohlii Briq. Planta Medica 58: 324–327.Google Scholar
Sen, J, Sharma, AK, Sahu, NP and Mahato, SB (1993) Forskolin production in untransformed root culture of Coleus forskohlii. Phytochemistry 34: 1309–1312.Google Scholar
Sevón, N and Oksman-Caldentey, K-M (2002) Agrobacterium rhizogenes -mediated transformation: root cultures as a source of alkaloids. Planta Medica 68: 859–868.CrossRefGoogle ScholarPubMed
Shanks, JV and Morgan, J (1999) Plant hairy root culture. Current Opinions in Biotechnology 10: 151–155.CrossRefGoogle ScholarPubMed
Sharma, K and Dandiya, PC (1992) Withania somnifera Dunal: present status. Indian Drugs 29: 247Google Scholar
Sharma, N and Chandel, KPS (1992) Effect of ascorbic acid on axillary shoot induction in Tylophora indica (Burm. f.) Merrill. Plant Cell, Tissue and Organ Culture 29: 109–113.CrossRefGoogle Scholar
Sharma, N, Chandel, KPS and Srivastav, VK (1991) In vitro propagation of Coleus forskohlii Briq., a threatened medicinal plant. Plant Cell Reports 10: 324–327.Google Scholar
Sivakumar, G and Krishnamurthy, KV (2004) In vitro organogenetic responses of Gloriosa superba. Russian Journal of Plant Physiology 51: 713–721.Google Scholar
Srivastav, SK, Chaubey, M, Khatoon, S, Rawat, AKS and Mehrotra, S (2002) Pharmacognostic evaluation of Coleus forskohlii. Pharmaceutical Biology 40: 129–134.Google Scholar
Srivastava, R (2000) Studying the information needs of medicinal plant stakeholders in Europe. TRAFFIC Dispatches 15: 5Google Scholar
Stærk, D, Lykkeberg, AK, Christensen, J, Budnik, BA, Abe, F and Jaroszewski, JW (2002) In vitro cytotoxic activity of phenanthroindolizidine from Cynanchum vincetoxicum and Tylophora tanakae against drug-sensitive and multidrug-resistant cancer cells. Journal of Natural Products 65: 1299–1302.Google Scholar
Subroto, MA, Hamill, JD and Doran, PM (1995) Growth kinetics and stoichiometry of Mentha citrata shooty teratomas transformed by Agrobacterium tumefaciens. Biotechnology Letters 17: 427–432.Google Scholar
Vishwakarma, RA, Tyagi, BR, Ahmed, B and Husain, A (1988) Variation in forskolin content in the roots of Coleus forskohlii. Planta Medica 54: 471–472.Google Scholar
Vitali, G, Conte, L and Nicoletti, M (1996) Withanolide composition and in vitro culture of Italian Withania somnifera. Planta Medica 62: 287–288.Google Scholar
Wiegrebe, W, Faber, L, Brockmann, H, Budzikiewicz, H, Krüger, U (1969) Alkaloids from Cynanchum vincetoxicum (L) Pers. Justus Liebigs Annals of Chemistry 721: 154–162.CrossRefGoogle ScholarPubMed
Wysham, DG, Brotherton, AF and Heistad, DD (1986) Effects of forskolin on cerebral blood flow: implications for the role of adenylate cyclase. Stroke 17: 1299–1303.CrossRefGoogle ScholarPubMed
Yoshida, K, Hayashi, T and Sano, K (1988) Colchicine precursors and the formation of alkaloids in suspension cultured Colchicum autumnale. Phytochemistry 27: 1375–1378.Google Scholar
Yu, PLC, El-Olemy, MM and Stohs, SJ (1974) A phytochemical invstigation of Withania somnifera tissue cultures. Lloydia 37: 593–597.Google Scholar
Zhong, JJ (2001) Biochemical engineering of the production of plant-specific secondary metabolites by cell suspension cultures. In: Scheper, Th (ed.) Advances in Biochemical Engineering/Biotechnology, Vol. 72. Berlin: Springer-Verlag, 1–26.Google Scholar
Zupan, J and Zambryski, P (1995) Transfer of T-DNA from Agrobacterium to the plant cell. Plant Physiology 107: 1041–1047.Google Scholar