Ergot Alkaloids and their Hallucinogenic Potential in Morning Glories

Abstract

Naturally occurring and semisynthetic ergot alkaloids play a role in health care or as recreational drugs in Western and indigenous Mexican societies. Evidence is summarized that ergot alkaloids present in Central American Convolvulaceae like Turbina corymbosa, Ipomoea violacea, and Ipomoea asarifolia are colonized by different species of a newly described clavicipitaceous fungal genus named Periglandula. The fungi are associated with peltate glandular trichomes on the adaxial leaf surface of its host plants. The Periglandula fungi are not yet culturable in vitro but were demonstrated to have the capacity to synthesize ergot alkaloids. The alkaloids do not remain in the fungal mycelium but are translocated via the glandular trichomes into their plant host. Both fungi and host benefit from a symbiotic lifestyle. In evolutionary terms the alkaloid biosynthetic gene cluster in the Periglandula/Ipomoea symbiosis is likely to have a conserved (basic) structure while biosynthetic ergot gene clusters within the genera Claviceps and Epichloe were under ecological selection for alkaloid diversification.

Key words

Ipomoea asarifolia - Turbina corymbosa - Convolvulaceae - Clavicipitaceae - Periglandula - ergot alkaloids - hallucinogens

• References

• 1 Homöopatisches Arzneibuch (HAB 2008). Amtliche Ausgabe. Stuttgart: Deutscher Apotheker Verlag; 1991: 387-391
• 2 Giger RKA, Engel G. Albert Hofmannʼs pioneering work on ergot alkaloids and its impact on the search of novel drugs at Sandoz, a predecessor company of Novartis. Chimia (Aarau) 2006; 60: 83-87
• 3 Gröger D, Floss H. Biochemistry of Ergot Alkaloids – Achievements and Challenges. In: Cordell GA, ed. The Alkaloids: Chemistry and Biology, Vol. 50. New York: Academic Press; 1998; 50: 171-218
• 4 Rehacek Z, Sajdl P. Ergot Alkaloids, Chemistry, biological Effects, Biotechnology. Praha: Academia; 1990
• 5 Gröger D. Ergot. In: Kadis S, Ciegler A, Ajl SJ. eds. Microbial Toxins. New York: Academic Press; 1972: 321-373
• 6 Schardl CL, Panaccione DG, Tudzynski P. Ergot Alkaloids – Biology and molecular Biology. In: Cordell GA. ed. The Alkaloids: Chemistry and Biology, Vol. 63. New York: Academic Press; 2006: 45-86
• 7 Schardl CL. Introduction to special issue on ergot alkaloids. Toxins (Basel) 2015; 7: 4232-4237
• 8 Schultes RE, Hofmann A. The Botany and Chemistry of Hallucinogens. Springfield: Charles C Thomas; 1973: 240-257
• 9 Hofmann A. Die Wirkstoffe der Mexikanischen Zauberdroge „Ololiuqui“. Planta Med 1961; 9: 354-367
• 10 Eich E. Solanaceae and Convolvulaceae: secondary Metabolites. Berlin, Heidelberg: Springer; 2008
• 11 Scott PM. Ergot alkaloids: extent of human and animal exposure. World Mycotoxin J 2009; 2: 141-149
• 12 Schmersahl P. Mutterkorn: Halluzinogen und Auslöser von Vergiftungen. Dtsch Apoth Ztg 2010; 150: 48-52
• 13 Caporael LR. Ergotism: the satan loosed in Salem? Convulsive ergotism may have been a physiological basis for the Salem witchcraft crisis in 1692. Science 1976; 192: 21-26
• 14 Eadie MJ. Convulsive ergotism: epidemics of the serotonin syndrome?. Lancet Neurol 2003; 2: 429-434
• 15 Klotz JL. Activities and effects of ergot alkaloids on livestock physiology and production. Toxins (Basel) 2015; 7: 2801-2821
• 16 Schardl CL, Leuchtmann A. The Epichloe Endophytes of Grasses and the symbiotic Continuum. In: Dighton J, White jr. JF, Oudemans PV. eds. The fungal Community: its Organisation and Role in the Ecosystems, Vol. 23. Boca Raton: CRC Taylor and Francis; 2005: 475-503
• 17 Porter JK, Thompson jr. FN. Effects of fescue toxicosis on reproduction in livestock. J Anim Sci 1992; 70: 1594-1603
• 18 Dinkins RD, Nagabhyru P, Graham MA, Boykin D, Schardl CL. Transcriptome response of Lolium arundinaceum to its fungal endophyte Epichloe coenophiala . New Phytol 2016; 213: 324-337
• 19 Negard M, Uhlig S, Kauserud H, Andersen T, Hoiland K, Vralstad T. Links between genetic groups, indole alkaloid profiles and ecology within the grass-parasitic Claviceps purpurea species complex. Toxins (Basel) 2015; 7: 1431-1456
• 20 Hernandez F, Recchi NA, Lynceus JT. Rerum Medicarum Novae Hispaniae Thesaurus. 3rd ed.. ed. Rome: 1651: 145-146
• 21 Wink M. Interference of Alkaloids with Neuroreceptors and Ion Channels. In: Atta-Ur-Rahman. ed. Studies in Natural Products Chemistry, Vol. 11. New York: Elsevier; 2000: 3-122
• 22 Schultes RE, Hofmann A. Plants of the Gods. Their sacred, healing and hallucinugenic Powers. Rochester: Healing Arts Press; 1992: 178
• 23 Emboden W. Narcotic Plants. London: Studio Vista; 1972: 26
• 24 Paulke A, Kremer C, Toennes SW. Argyreia nervosa: Erfahrungen mit einem pflanzlichen Legal High. Pharmakon 2013; 1: 463-469
• 25 Stauffacher D, Tscherter H, Hofmann A. Isolierung von Ergosin und Ergosinin neben Agroclavin aus den Samen von Ipomoea argyrophylla VATKE (Convolvulaceae). Helv Chim Acta 1965; 6: 1379-1380
• 26 Leistner E, Steiner U. Fungal Origin of ergoline Alkaloids present in dicotyledonous Plants (Convolvulaceae). In: Esser K. ed. The Mycota, Vol. 15. Berlin, Heidelberg: Springer; 2006: 197-208
• 27 Steiner U, Leistner E. Ergoline alkaloids in convolvulaceous host plants originate from epibiotic clavicipitaceous fungi of the genus Periglandula . Fungal Ecol 2012; 5: 316-321
• 28 Eserman LA, Tiley GP, Jarret RL, Leebens-Mack JH, Miller RE. Phylogenetics and diversification of Morning Glories (Tribe Ipomoeeae, Convolvulaceae) based on whole plastome sequences. Am J Bot 2014; 101: 1-12
• 29 Kucht S, Groß J, Hussein Y, Grothe T, Keller U, Basar S, König WA, Steiner U, Leistner E. Elimination of ergoline alkaloids following treatment of Ipomoea asarifolia (Convolvulaceae) with fungicides. Planta 2004; 219: 619-625
• 30 Mothes K, Schütte HR, Luckner M. Biochemistry of Alkaloids. Berlin: VEB Deutscher Verlag der Wissenschaften; 1985: 54
• 31 Hellwig S. Ergolinvorkommen bei Convolvulaceen. Biochemische und ökologische Interaktionen einer Pflanze-Pilz-Symbiose [Dissertation]. Bonn: Rheinische Friedrich-Wilhelms-Universität; 2007
• 32 Beaulieu WT, Panaccione DG, Hazekamp CS, Mckee MC, Ryan KL, Clay K. Differential allocation of seed-borne ergot alkaloids during early ontogeny of Morning Glories (Convolvulaceae). J Chem Ecol 2013; 39: 919-930
• 33 Hofmann A. LSD – mein Sorgenkind, die Entdeckung einer „Wunderdroge“. 12. Aufl.. München: dtv; 1993: 132
• 34 Steiner U, Leibner S, Schardl CL, Leuchtmann A, Leistner E. Periglandula, a new fungal genus within the Clavicipitaceae and its association with Convolvulaceae. Mycologia 2011; 103: 1133-1145
• 35 Ahimsa-Müller MA, Markert A, Hellwig S, Knoop V, Steiner U, Drewke C, Leistner E. Clavicipitaceous fungi associated with ergoline alkaloid-containing Convolvulaceae. J Nat Prod 2007; 70: 1955-1960
• 36 Steiner U, Ahimsa-Müller MA, Markert A, Kucht S, Groß J, Kauf N, Kuzma M, Zych M, Lamshöft M, Furmanowa M, Knoop V, Drewke C, Leistner E. Molecular characterization of a seed transmitted clavicipitaceous fungus occurring on dicotyledonous plants (Convolvulaceae). Planta 2006; 224: 533-544
• 37 Beaulieu WT, Panaccione DG, Ryan KL, Kaonongbua W. Phylogenetic and chemotypic diversity of Periglandula species in eight new Morning Glory hosts (Convolvulaceae). Mycologia 2015; 107: 667-678
• 38 Markert A, Steffan N, Ploss K, Hellwig S, Steiner U, Drewke C, Li SM, Boland W, Leistner E. Biosynthesis and accumulation of ergoline alkaloids in a mutualistic association between Ipomoea asarifolia (Convolvulaceae) and a clavicipitalean fungus. Plant Physiol 2008; 147: 296-305
• 39 Schardl CL, Young CA, Hesse U, Amyotte SG, Andreeva K, Calie PJ, Fleetwood DJ, Haws DC, Moore N, Oeser B, Panaccione DG, Schweri KK, Voisey CR, Farman ML, Jaromczyk JW, Roe BA, OʼSullivan DM, Scott B, Tudzynski P, An Z, Arnaoudova EG, Bullock CT, Charlton ND, Chen L, Cox M, Dinkins RD, Florea S, Glenn AE, Gordon A, Güldener U, Harris DR, Hollin W, Jaromczyk J, Johnson RD, Khan AK, Leistner E, Leuchtmann A, Li C, Liu J, Liu J, Liu M, Mace W, Machado C, Nagabhyru P, Pan J, Schmid J, Sugawara K, Steiner U, Takach JE, Tanaka E, Webb JS, Wilson EV, Wiseman JL, Yoshida R, Zeng Z. Plant symbiotic fungi as chemical engineers: multi-genome analysis of the Clavicipitaceae reveals dynamics of alkaloid loci. PLoS Genet 2013; 9: e1003323
• 40 Florea S, Panaccione DG, Schardl CL. Ergot alkaloids of the family Clavicipitaceae. Phytopathology 2017; 5: 504-518
• 41 Steiner U, Hellwig S, Leistner R. Specificity in the interaction between an epibiotic clavicipitalean fungus and its convolvulaceous host in a fungus/plant symbiotum. Plant Signal Behav 2008; 3: 704-706
• 42 Hassan NS, Hashem E, Amine GH, Hussein Y, El-Zawahry YA, Leistner E. Biochemical detection of ergoline alkaloids in Rivea corymbosa L. (Convolvulaceae) cell suspension cultures. Egypt J Biotechnol 2004; 16: 331-349
• 43 Wallway C, Li SM. Ergot alkaloids: structure diversity, biosynthetic gene clusters and functional proof of biosynthetic genes. Nat Prod Rep 2011; 28: 496-510
• 44 Steiner U, Kucht S, Ahimsa-Müller MA, Grundmann N, Li SM, Drewke C, Leistner E. The key role of peltate glandular trichomes in symbiota comprising clavicipitaceous fungi of the genus Periglandula and their host plants. Toxins (Basel) 2015; 7: 1355-1373
• 45 Young CA, Schardl CL, Panaccione DG, Florea S, Takach JE, Charlton ND, Moore N, Webb JS, Jaromczyk J. Genetics, genomics and evolution of ergot alkaloid diversity. Toxins (Basel) 2015; 7: 1273-1302
• 46 Gerhards N, Neubauer L, Tudzynski P, Li SM. Biosynthetic pathways of ergot alkaloids. Toxins (Basel) 2014; 6: 3281-3295
• 47 Wacker D, Wang S, McCorvy JD, Betz RM, Venkatakrishnan AJ, Levit A, Lansu K, Schools ZL, Che T, Nichols DE, Shoichet BK, Dror RO, Roth BL. Cristal structure of an LSD-bound human serotonin receptor. Cell 2017; 168: 377-389
• 48 Eisner T. For Love of Insects. Cambridge: Harvard University Press; 2003
• 49 Harborne JB. Introduction to Ecological Biochemistry, 4th ed. London: Academic Press; 2004
• 50 Gunatilaka AAL. Natural products from plant-associated microorganisms: distribution, bioactivity, and implications of their occurrence. J Nat Prod 2006; 69: 509-526
• 51 Floss HG. Combinatorial biosynthesis-potential and problems. J Biotech 2006; 124: 242-257
• 52 Bérdy J. Bioactive microbial metabolites. A personal view. J Antibiot 2005; 58: 1-26
• 53 Crosignani PG. Current treatment issues in female hyperprolactinaemia. Science Direct 2006; 125: 152-164
• 54 de Groot NJA, van Dongen PWJ, Vree TB, Hekster YA, van Roosmalen L. Ergot alkaloids, current status and review of clinical pharmacology and therapeutic use compared with other oxytocics in obstetrics and gynaecology. Drugs 1998; 56: 523-535
• 55 Burn D. Parkinsonʼs disease: treatment. Pharm J 2000; 264: 476-479
• 56 LAUER-TAXE R Datenbank. Version: WEBAPO R Info-system. Date: April 15, 2017. Keywords: ergotamine or cabergoline or dihydroergocristin or bromocriptine.
• 57 Rote Liste Service GmbH. ed. Arzneimittelverzeichnis für Deutschland. Frankfurt/Main: Rote Liste Service GmbH; 2016
• 58 Nuhn P. Die Wunderdroge. Vor 70 Jahren wurde die Wirkung des LSD entdeckt. Dtsch Apoth Ztg 2013; 153: 70-71
• 59 Winkelmann M. Psychedelics as medicines for substance abuse rehabilitation: evaluating treatments with LSD, Peyote, Ibogaine and Ayahuasca. Curr Drug Abuse Rev 2014; 7: 101-116
• 60 Liester MB. A review of lysergic acid diethylamide (LSD) in the treatment of addictions: historical perspectives and future prospects. Curr Drug Abuse Rev 2014; 7: 146-156