Download PDF
Planta Med 2015; 81(12/13): 995-1002
DOI: 10.1055/s-0035-1546182
Reviews
Georg Thieme Verlag KG Stuttgart · New York

The Genus Diphasiastrum and Its Lycopodium Alkaloids[*]

Elsa Steinunn Halldorsdottir
Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland Hagi, Reykjavik, Iceland
,
Natalia Magdalena Kowal
Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland Hagi, Reykjavik, Iceland
,
Elin Soffia Olafsdottir
Faculty of Pharmaceutical Sciences, School of Health Sciences, University of Iceland Hagi, Reykjavik, Iceland
› Author Affiliations
Further Information

Publication History

received 14 March 2015
revised 08 May 2015

accepted 14 May 2015

Publication Date:
17 July 2015 (online)

Also available at
   Permissions and Reprints

Abstract

The genus Diphasiastrum includes at least 23 species distributed primarily across the northern temperate and subarctic areas of the world. These plants produce an array of lycopodium alkaloids, and some species such as Diphasiastrum complanatum have been used in traditional medicine for ages for various conditions. Hybridization is common in this group of plants and they have always been a challenge for taxonomists and other scientists studying them. To date, 11 Diphasiastrum species have been reported to produce lycopodium alkaloids. In this review, reported alkaloids and their distribution patterns across these species along with taxonomical and bioactivity considerations are reviewed and discussed.

Key words

Diphasiastrum - Lycopodiaceae - classification - lycopodium alkaloids

* Dedicated to Professor Dr. Dr. h. c. mult. Adolf Nahrstedt on the occasion of his 75th birthday.


 

  • References

  • 1 Halldorsdottir ES, Palmadottir RH, Nyberg NT, Olafsdottir ES. Phytochemical analysis of alkaloids from the Icelandic club moss Diphasiastrum alpinum . Phytochem Lett 2013; 6: 355-359
    CrossrefPubMedGoogle Scholar
  • 2 Wikstrom N, Kenrick P. Evolution of Lycopodiaceae (Lycopsida): estimating divergence times from rbcL gene sequences by use of nonparametric rate smoothing. Mol Phylogenet Evol 2001; 19: 177-186
    CrossrefPubMedGoogle Scholar
  • 3 Gensel PG, Berry CM. Early lycophyte evolution. Am Fern J 2001; 91: 74-98
    CrossrefPubMedGoogle Scholar
  • 4 Bennert HW, Horn K, Kauth M, Fuchs J, Jakobsen ISB, Ollgaard B, Schnittler M, Steinberg M, Viane R. Flow cytometry confirms reticulate evolution and reveals triploidy in Central European Diphasiastrum taxa (Lycopodiaceae, Lycophyta). Ann Bot 2011; 108: 867-876
    CrossrefPubMedGoogle Scholar
  • 5 Wagner WH, Beitel JM. Generic classification of modern North-American Lycopodiaceae. Ann Mo Bot Gard 1992; 79: 676-686
    CrossrefPubMedGoogle Scholar
  • 6 Hirasawa Y, Kobayashi J, Morita H. The Lycopodium alkaloids. Heterocycles 2009; 77: 679-729
    CrossrefPubMedGoogle Scholar
  • 7 Ma XQ, Gang DR. The Lycopodium alkaloids. Nat Prod Rep 2004; 21: 752-772
    CrossrefPubMedGoogle Scholar
  • 8 Siengalewicz P, Mulzer J, Rinner U. Lycopodium alkaloids – synthetic highlights and recent developments. Alkaloids Chem Biol 2013; 72: 1-151
    PubMedGoogle Scholar
  • 9 Johannsdottir AL. Íslenskar lækningajurtir: söfnun þeirra, notkun og áhrif. Reykjavík: Bókaútgáfan Örn og Örlygur; 1992
    Google Scholar
  • 10 Róbertsdóttir AR. Íslenskar lækningajurtir, notkun þeirra, tínsla og rannsóknir. Reykjavík: Litróf, Hagprent ehf; 2011
    Google Scholar
  • 11 Orhan IE, Sener B, Kaiser M, Brun R, Tasdemir D. Antiprotozoal activity and cytotoxicity of Lycopodium clavatum and Lycopodium complanatum subsp. chamaecyparissus extracts. Turk J Biochem 2013; 38: 403-408
    PubMedGoogle Scholar
  • 12 Mamedov N, Gardner Z, Craker LE. Medicinal plants used in Russia and Central Asia for the treatment of selected skin conditions. J Herbs Spices Med Plants 2005; 11: 191-222
    CrossrefPubMedGoogle Scholar
  • 13 Cheng JT, Liu F, Li XN, Wu XD, Dong LB, Peng LY, Huang SX, He J, Zhao QS. Lycospidine A, a new type of lycopodium alkaloid from Lycopodium complanatum . Org Lett 2013; 15: 2438-2441
    CrossrefPubMedGoogle Scholar
  • 14 Konrath EL, Neves BM, Lunardi PS, Passos Cdos S, Simões-Pires A, Ortega MG, Gonçalves CA, Cabrera JL, Moreira JCF, Henriques AT. Investigation of the in vitro and ex vivo acetylcholinesterase and antioxidant activities of traditionally used Lycopodium species from South America on alkaloid extracts. J Ethnopharmacol 2012; 139: 58-67
    CrossrefPubMedGoogle Scholar
  • 15 Ma XQ, Tan CH, Zhu DY, Gang DR, Xiao PG. Huperzine A from Huperzia species – an ethnopharmacolgical review. J Ethnopharmacol 2007; 113: 15-34
    CrossrefPubMedGoogle Scholar
  • 16 Olafsdóttir E, Halldorsdottir E, Pich NM, Omarsdottir S. Lycopodium alkaloids: pharmacology. In: Ramawat KG, Mérillon J-TM, editors Natural products. Berlin Heidelberg: Springer; 2013: 1239-1262
    CrossrefGoogle Scholar
  • 17 Holub J. Transfers of Lycopodium species to Huperzia: with a note on generic classification in Huperziaceae. Folia Geobot 1985; 20: 67-80
    PubMedGoogle Scholar
  • 18 Øllgaard B. A revised classification of the Lycopodiaceae s. lat. Opera Bot 1987; 92: 153-178
    PubMedGoogle Scholar
  • 19 Ching RC. The Chinese fern families and genera: systematic arrangement and historical origin. Acta Phytotax Sin 1978; 16: 1-19
    PubMedGoogle Scholar
  • 20 Prieto JAF, Aguiar C, Dias E, Casado M, Homet J. The genus Huperzia (Lycopodiaceae) in the Azores and Madeira. Bot J Linn Soc 2008; 158: 522-533
    CrossrefPubMedGoogle Scholar
  • 21 Holub J. Diphasiastrum, a new genus of Lycopodiaceae. Preslia 1975; 47: 97-110
    PubMedGoogle Scholar
  • 22 Kukkonen I. Notes on the treatment of the family Lycopodiaceae for Flora Nordica. Ann Bot Fenn 1994; 31: 197-202
    PubMedGoogle Scholar
  • 23 Kukkonen I. Lycopodiaceae. In: Jonsell B, editor Flora Nordica. Stockholm: Bergius Foundation; 2000: 1-13
    Google Scholar
  • 24 Hanusova K, Ekrt L, Vit P, Kolar F, Urfus T. Continuous morphological variation correlated with genome size indicates frequent introgressive hybridization among Diphasiastrum species (Lycopodiaceae) in Central Europe. PLoS One 2014; 9: 1-13
    PubMedGoogle Scholar
  • 25 Bennert HW, Suksathan P, Horn K. Diphasiastrum multispicatum (J.H. Wilce) Holub (Lycopodiaceae) in Thailand. Am Fern J 2007; 97: 155-165
    CrossrefPubMedGoogle Scholar
  • 26 Aagaard SMD, Greilhuber J, Zhang XC, Wikström N. Occurrence and evolutionary origins of polyploids in the clubmoss genus Diphasiastrum (Lycopodiaceae). Mol Phylogenet Evol 2009; 52: 746-754
    CrossrefPubMedGoogle Scholar
  • 27 Stoor AM, Boudrie M, Jérome C, Horn K, Bennert HW. Diphasiastrum oellgaardii (Lycopodiaceae, Pteridophyta), a new lycopod species from Central Europe and France. Feddes Repert 1996; 107: 149-157
    PubMedGoogle Scholar
  • 28 Aagaard SMD, Vogel JC, Wikstrom N. Resolving maternal relationships in the clubmoss genus Diphasiastrum (Lycopodiaceae). Taxon 2009; 58: 835-848
    PubMedGoogle Scholar
  • 29 Muller S, Jérôme C, Horn K. Importance of secondary habitats and need for ecological management for the conservation of Diphasiastrum tristachyum (Lycopodiaceae, Pteridophyta) in the Vosges Mountains (France). Biodivers Conserv 2003; 12: 321-332
    CrossrefPubMedGoogle Scholar
  • 30 Ayer WA, Trifonov LS. Lycopodium alkaloids. In: Cordell GA, Brossi A, editors The alkaloids: chemistry and pharmacology. New York: Academic Press, Inc.; 1994: 233-266
    Google Scholar
  • 31 Bödeker K. Lycopodin, das erste Alkaloid der Gefässkryptogamen. Justus Liebigs Ann Chem 1881; 208: 363-367
    CrossrefPubMedGoogle Scholar
  • 32 Hardardottir I, Olafsdottir ES, Freysdottir J. Dendritic cells matured in the presence of the lycopodium alkaloid annotine direct T cell responses toward a Th2/Treg phenotype. Phytomedicine 2015; 22: 277-282
    CrossrefPubMedGoogle Scholar
  • 33 Orhan I, Kupeli E, Sener B, Yesilada E. Appraisal of anti-inflammatory potential of the clubmoss, Lycopodium clavatum L. J Ethnopharmacol 2007; 109: 146-150
    CrossrefPubMedGoogle Scholar
  • 34 Ruan QW, Hu XN, Ao HF, Ma HF, Gao ZJ, Liu F, Kong DQ, Bao ZJ, Yu ZW. The neurovascular protective effects of huperzine a on D-galactose-induced inflammatory damage in the rat hippocampus. Gerontology 2014; 60: 424-439
    CrossrefPubMedGoogle Scholar
  • 35 Tian GX, Zhu XQ, Chen Y, Wu GC, Wang J. Huperzine A inhibits CCL2 production in experimental autoimmune encephalomyelitis mice and in cultured astrocytes. Int J Immunopathol Pharmacol 2013; 26: 757-764
    PubMedGoogle Scholar
  • 36 Wang J, Chen F, Zheng P, Deng WJ, Yuan J, Peng B, Wang RC, Liu WJ, Zhao H, Wang YQ, Wu GC. Huperzine A ameliorates experimental autoimmune encephalomyelitis via the suppression of T cell-mediated neuronal inflammation in mice. Exp Neurol 2012; 236: 79-87
    CrossrefPubMedGoogle Scholar
  • 37 Zhang HY, Zheng CY, Yan H, Wang ZF, Tang LL, Gao X, Tang XC. Potential therapeutic targets of huperzine A for Alzheimerʼs disease and vascular dementia. Chem Biol Interact 2008; 175: 396-402
    CrossrefPubMedGoogle Scholar
  • 38 Morita H, Ishiuchi K, Haganuma A, Hoshino T, Obara Y, Nakahata N, Kobayashi J. Complanadine B, obscurumines A and B, new alkaloids from two species of Lycopodium . Tetrahedron 2005; 61: 1955-1960
    CrossrefPubMedGoogle Scholar
  • 39 Ishiuchi K, Kubota T, Ishiyama H, Hayashi S, Shibata T, Mori K, Obara Y, Nakahata N, Kobayashi J. Lyconadins D and E, and complanadine E, new Lycopodium alkaloids from Lycopodium complanatum . Bioorg Med Chem 2011; 19: 749-753
    CrossrefPubMedGoogle Scholar
  • 40 Johnson T, Siegel D. Complanadine A, a selective agonist for the Mas-related G protein-coupled receptor X2. Bioorg Med Chem Lett 2014; 24: 3512-3515
    CrossrefPubMedGoogle Scholar
  • 41 Liu JS, Zhu YL, Yu CM, Zhou YZ, Han YY, Wu FW, Qi BF. The structures of huperzine-A and huperzine-B, 2 new alkaloids exhibiting marked anticholinesterase activity. Can J Chem 1986; 64: 837-839
    CrossrefPubMedGoogle Scholar
  • 42 Zhang DB, Chen JJ, Song QY, Zhang L, Gao K. Lycodine-type alkaloids from Lycopodiastrum casuarinoides and their acetylcholinesterase inhibitory activity. Molecules 2014; 19: 9999-10010
    CrossrefPubMedGoogle Scholar
  • 43 Ho R, Marsousi N, Eugster P, Bianchini JP, Raharivelomanana P. Detection by UPLC/ESI-TOF-MS of alkaloids in three Lycopodiaceae species from French Polynesia and their anticholinesterase activity. Nat Prod Commun 2009; 4: 1349-1352
    PubMedGoogle Scholar
  • 44 Miller N, Mees F, Braekman JC. Alcaloides de Lycopodium alpinum . Phytochemistry 1971; 10: 1931-1934
    CrossrefPubMedGoogle Scholar
  • 45 Halldorsdottir ES, Jaroszewski JW, Olafsdottir ES. Acetylcholinesterase inhibitory activity of lycopodane-type alkaloids from the Icelandic Lycopodium annotinum ssp. alpestre . Phytochemistry 2010; 71: 149-157
    CrossrefPubMedGoogle Scholar
  • 46 Staerk D, Larsen J, Larsen LA, Olafsdottir ES, Witt M, Jaroszewski JW. Selagoline, a new alkaloid from Huperzia selago . Nat Prod Res 2004; 18: 197-203
    CrossrefPubMedGoogle Scholar
  • 47 Braekman JC, Nyembo L, Bourdoux P, Kahindo N, Hootele C. Distribution des alcaloides dans le genre Lycopodium . Phytochemistry 1974; 13: 2519-2528
    CrossrefPubMedGoogle Scholar
  • 48 Ma X, Gang DR. The Lycopodium alkaloids. Nat Prod Rep 2004; 21: 752-772
    CrossrefPubMedGoogle Scholar
  • 49 Wu XD, He J, Xu G, Peng L, Song LD, Zhao QS. Diphaladine A, a new lycopodium alkaloid from Diphasiastrum complanatum (Lycopodiaceae). Acta Bot Yunn 2009; 31: 93-96
    PubMedGoogle Scholar
  • 50 Ishiuchi K, Kubota T, Mikami Y, Obara Y, Nakahata N, Kobayashi J. Complanadines C and D, new dimeric alkaloids from Lycopodium complanatum . Bioorg Med Chem 2007; 15: 413-417
    CrossrefPubMedGoogle Scholar
  • 51 Kubota T, Yahata H, Ishiuchi K, Obara Y, Nakahata N, Kobayashia J. Lycopladine E, a new C(16)N(1)-type alkaloid from Lycopodium complanatum . Heterocycles 2007; 74: 843-848
    CrossrefPubMedGoogle Scholar
  • 52 Kobayashi J, Hirasawa Y, Yoshida N, Morita H. Complanadine A, a new dimeric alkaloid from Lycopodium complanatum . Tetrahedron Lett 2000; 41: 9069-9073
    CrossrefPubMedGoogle Scholar
  • 53 Kobayashi J, Hirasawa Y, Yoshida N, Morita H. Lyconadin A, a novel alkaloid from Lycopodium complanatum . J Org Chem 2001; 66: 5901-5904
    CrossrefPubMedGoogle Scholar
  • 54 Ishiuchi K, Kubota T, Ishiyama H, Hayashi S, Shibata T, Mori K, Obara Y, Nakahata N, Kobayashi J. Lyconadins D and E, and complanadine E, new Lycopodium alkaloids from Lycopodium complanatum . Bioorg Med Chem 2011; 19: 749-753
    CrossrefPubMedGoogle Scholar
  • 55 Ishiuchi K, Kubota T, Hayashi S, Shibata T, Kobayashi J. Lycopladines F and G, new C16N2-type alkaloids with an additional C4N unit from Lycopodium complanatum . Tetrahedron Lett 2009; 50: 4221-4224
    CrossrefPubMedGoogle Scholar
  • 56 Ishiuchi K, Kubota T, Hoshino T, Obara Y, Nakahata N, Kobayashi J. Lycopladines B–D and lyconadin B, new alkaloids from Lycopodium complanatum . Bioorg Med Chem 2006; 14: 5995-6000
    CrossrefPubMedGoogle Scholar
  • 57 Ishiuchi K, Kubota T, Ishiyama H, Hayashi S, Shibata T, Kobayashi J. Lyconadins C and F, new Lycopodium alkaloids from Lycopodium complanatum . Tetrahedron Lett 2011; 52: 289-292
    CrossrefPubMedGoogle Scholar
  • 58 Ishiuchi K, Kubota T, Morita H, Kobayashi J. Lycopladine A, a new C16 N alkaloid from Lycopodium complanatum . Tetrahedron Lett 2006; 47: 3287-3289
    CrossrefPubMedGoogle Scholar
  • 59 Ishiuchi K, Kubota T, Hayashi S, Shibata T, Kobayashi J. Lycopladine H, a novel alkaloid with fused-tetracyclic skeleton from Lycopodium complanatum . Tetrahedron Lett 2009; 50: 6534-6536
    CrossrefPubMedGoogle Scholar
  • 60 Harrison WA, Curcumelli-Rodostamo M, Carson DF, Barclay LRC, MacLean DB. Lycopodium alkaloids: X. The structure of lycopodine. Can J Chem 1961; 39: 2086-2099
    CrossrefPubMedGoogle Scholar
  • 61 Curcumelli-Rodostamo M, MacLean DB. Lycopodium alkaloids: XII. Flabelliformine. Can J Chem 1962; 40: 1068-1070
    CrossrefPubMedGoogle Scholar
  • 62 Douglas B, Lewis DG, Marion L. The alkaloids of Lycopodium species: XII. Relationship between some of the minor alkaloids and lycopodine. Can J Chem 1953; 31: 272-276
    CrossrefPubMedGoogle Scholar
  • 63 Alam SN, Adams KAH, MacLean DB. Lycopodium alkaloids: XV. Structure and mass spectra of some minor alkaloids of L. flabelliforme . Can J Chem 1964; 42: 2456-2466
    CrossrefPubMedGoogle Scholar
  • 64 Young JCF, MacLean DB. Lycopodium alkaloids: XIV. Flabelline. Can J Chem 1963; 41: 2731-2736
    CrossrefPubMedGoogle Scholar
  • 65 Moore BP, Marion L. α-Obscurine and β-obscurine: Structure studies. Can J Chem 1953; 31: 952-957
    CrossrefPubMedGoogle Scholar
  • 66 Burnell RH. Lycopodium alkaloids. I. Extraction of alkaloids from Lycopodium fawcettii . J Chem Soc 1959; 3091-3093
    PubMedGoogle Scholar
  • 67 Burnell RH, Mootoo BS, Taylor DR. Alkaloids of Lycopodium fawcettii. Part II. Can J Chem 1960; 38: 1927-1932
    CrossrefPubMedGoogle Scholar
  • 68 Burnell RH, Chin CG, Mootoo BS, Taylor DR. Lycopodium alkaloids: Part VIII. New alkaloids from Jamaican Lycopodium species. Can J Chem 1963; 41: 3091-3094
    CrossrefPubMedGoogle Scholar
  • 69 Ayer WA, Bowman WR, Kebarle P, Burnell RH. Structural studies by mass spectrometry: Determination of the structure of lycofawcine (base L). Can J Chem 1965; 43: 328-331
    CrossrefPubMedGoogle Scholar
  • 70 Inubushi Y, Ishii H, Harayama T, Burnell RH, Ayer WA, Altenkirk B. Structure of fawcettimine: Correlation with serratinine. Tetrahedron Lett 1967; 8: 1069-1072
    CrossrefPubMedGoogle Scholar
  • 71 Burnell RH, Chapelle A, Fischer J, Ricard L. Base R, the X-ray crystal structure of a novel lycopodium alkaloid. J Chem Soc Chem Commun 1974; 10: 391
    PubMedGoogle Scholar
  • 72 Ho R, Marsousi N, Eugster P, Bianchini JP, Raharivelomanana P. Detection by UPLC/ESI-TOF-MS of alkaloids in three Lycopodiaceae species from French Polynesia and their anticholinesterase activity. Nat Prod Commun 2009; 4: 1349-1352
    PubMedGoogle Scholar
  • 73 Ayer WA, Dikko S. Alkaloids of Lycopodium thyoides and L. contiguum . Phytochemistry 1974; 13: 653-654
    CrossrefPubMedGoogle Scholar
  • 74 Orhan I, Ozcelik B, Aslan S, Kartal M, Karaoglu T, Sener B, Terzioglu S, Iqbal Choudhary M. In vitro biological activity screening of Lycopodium complanatum L. ssp. chamaecyparissus (A. Br.) Doll. Nat Prod Res 2009; 23: 514-526
    CrossrefPubMedGoogle Scholar