Acta Biologica Hungarica

, Volume 68, Issue 4, pp 443–452 | Cite as

In vivo Screening of Diterpene Alkaloids using Bdelloid Rotifer Assays

  • Tivadar Kiss
  • Lilla Mácsai
  • Dezső CsuporEmail author
  • Zsolt László DatkiEmail author


The group of diterpene alkaloids contains numerous compounds with complex chemistry and diverse pharmacological activities. Beside toxicity, these compounds possess activity on the cardiovascular system, tumor cell lines and nervous system. The pharmacological properties have been described using in vitro and in vivo techniques; however, the bioactivities of many compounds have not thoroughly been studied. Here we report on the in vivo evaluation of ten diterpene alkaloids using bdelloid rotifer assays. Napelline exerted toxic effects on rotifers, while wide tolerance range was observed for other investigated compounds. Weak toxicity of songorine is supported by our experiment. Toxicological data for senbusine A, senbusine C, septentrioidine and hetisinone are reported for the first time.


Diterpenoid alkaloids toxicity Aconitum rotifers Philodina acuticornis odiosa 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ahmad, H., Ahmad, S., Shah, S., Latif, A., Ali, M. (2017) Antioxidant and anticholinesterase potential of diterpenoid alkaloids from Aconitum heterophyllum. Bioorg. Med. Chem. 25, 3368–3376.CrossRefGoogle Scholar
  2. 2.
    Ameri A. (1998) Effects of the Aconitum alkaloid songorine on synaptic transmission and pairedpulse facilitation of CA1 pyramidal cells in rat hippocampal slices. Br. J. Pharmacol. 125, 461–468.CrossRefGoogle Scholar
  3. 3.
    Ameri A. (1998) The effects of Aconitum alkaloids on the central nervous system. Prog. Neurobiol. 56, 211–235.CrossRefGoogle Scholar
  4. 4.
    Arcangeli, A., Becchetti, A. (2017) hERG channels: from antitargets to novel targets for cancer therapy. Clin. Cancer Res. 23, 3–5.CrossRefGoogle Scholar
  5. 5.
    Bisset, N. G. (1981) Arrow poisons in China. part II. Aconitum - botany, chemistry, and pharmacology. J. Ethnopharmacol. 4, 247–336.CrossRefGoogle Scholar
  6. 6.
    Chen D. H. (1984) Biological activities and medicinal potentialities of diterpene alkaloids. Chinese Trad. Herb. Med. 15, 180–184.Google Scholar
  7. 7.
    Csupor, D., Forgó, P., Wenzig, E. M., Bauer, R., Hohmann, J. (2008) Bisnorditerpene, norditerpene, and lipo-alkaloids from Aconitum toxicum. J. Nat. Prod. 71, 1779–1782.CrossRefGoogle Scholar
  8. 8.
    Csupor, D., Forgó, P., Csedő, K., Hohmann, J., Csedő, K., Hohmann, J. (2006) C19 and C20 Diterpene alkaloids from Aconitum toxicum Rchb. Helv. Chim. Act. 89, 2981–2986.CrossRefGoogle Scholar
  9. 9.
    Du, J., Lu, X., Long, Z., Zhang, Z., Zhu, X., Yang, Y. (2013) In vitro and in vivo anticancer activity of aconitine on melanoma cell line B16. Molecule. 18, 757–767.CrossRefGoogle Scholar
  10. 10.
    Dzhakhangirov, F. N., Sadritdinov, F. S. (1973) Antidepressive properties of the alkaloid songorine. Dokl. Akad. Nauk UzSS. 30, 39–40.Google Scholar
  11. 11.
    Dzhakhangirov, F. N., Sultankhodzhaev, M. N., Tashkhodzhaev, B., Salimov, B. T. (1997) Diterpenoid alkaloids as a new class of antiarrhythmic agents. Structure-activity relationship. Chem. Nat. Compd. 33, 190–202.CrossRefGoogle Scholar
  12. 12.
    Guo B. (2011) Effects of osthole, psoralen, aconitine on breast cancer MDA-MB-231BO cell line inhibition in vitro. J. Chinese Integr. Med. 9, 1110–1117.CrossRefGoogle Scholar
  13. 13.
    Hazawa, M., Takahashi, K., Wada, K., Mori, T., Kawahara, N., Kashiwakura, I. (2011) Structureactivity relationships between the Aconitum C20-diterpenoid alkaloid derivatives and the growth suppressive activities of Non-Hodgkin’s lymphoma Raji cells and human hematopoietic stem/progenitor cells. Invest. New Drug. 29, 1–8.CrossRefGoogle Scholar
  14. 14.
    de Inés, C., Reina, M., Gavín, J. A., González-Coloma, A. (2006) In vitro cytotoxicity of norditerpenoid alkaloids. Zeitschrift für Naturforsch. C. 61, 11–18.CrossRefGoogle Scholar
  15. 15.
    Ji, B. L., Xia, L. P., Zhou, F. X., Mao, G. Z., Xu, L. X. (2016) Aconitine induces cell apoptosis in human pancreatic cancer via NF-κB signaling pathway. Eur. Rev. Med. Pharmacol. Sci. 20, 4955–4964.PubMedGoogle Scholar
  16. 16.
    Kőszegi, Z., Atlasz, T., Csupor, D., Szabadfi, K., Hohmann, J., Hernádi, K. (2007) Aconitum alkaloid songorine acts as a potent GABAA receptor agonist in the rat brain in vivo. Acta Physiol. Hung. 94, 367–368.Google Scholar
  17. 17.
    Liang, Y., Chen, Z., Liu, L., Liu, S., Zhang, G. (2009) Chemical constituents of planted Aconitum flavum. Zhongcaoya. 40, 862–865.Google Scholar
  18. 18.
    Nesterova, Y. V., Povetieva, T. N., Suslov, N. I., Semenov, A. A., Pushkarskiy, S. V. (2011) Antidepressant activity of diterpene alkaloids of Aconitum baicalense Turcz. Bull. Exp. Biol. Med. 151, 425–428.CrossRefGoogle Scholar
  19. 19.
    Nesterova, Y. V., Povetieva, T. N., Suslov, N. I., Zyuzkov, G. N., Pushkarskii, S. V., Aksinenko, S. G., Schultz, E. E., Kravtsova, S. S., Krapivin, A. V. (2014) Analgesic activity of diterpene alkaloids from Aconitum baikalensis. Bull. Exp. Biol. Med. 157, 488–491.CrossRefGoogle Scholar
  20. 20.
    Nesterova, Y. V., Povetieva, T. N., Suslov, N. I., Zyuzkov, G. N., Aksinenko, S. G., Pushkarskii, S. V., Krapivin, A. V. (2014) Anti-inflammatory activity of diterpene alkaloids from Aconitum baikalense. Bull. Exp. Biol. Med. 156, 665–668.CrossRefGoogle Scholar
  21. 21.
    Povetieva, T. N., Suslov, N. I., Zhdanov, V. V., Hrichkova, T. Y., Udut, E. V., Chaykovskiy, A. S., Gaydamovich, N. N., Andreeva, T. I., Dygai, A. (2012) Regeneratory characteristics of complex extract and isolated diterpene alkaloids of Aconitum baikalense. Bull. Exp. Biol. Med. 152, 439–443.CrossRefGoogle Scholar
  22. 22.
    Niitsu, K., Chin, S., Fukuyama, K., Mihashi, H. (1992) Diterpene alkaloid and pharmaceuticals containing diterpene alkaloids for treatment of heart failure. Jpn. Kokai Tokkyo Koho. (JP04026676A): 7 pp.Google Scholar
  23. 23.
    Oláh, Z., Bush, A. I., Dávid, A., Gálik, B., Ivitz, E., Mácsai, L., Karman, Z., Janka, Z., Datki, Zs. (2017) Novel in vivo experimental viability assays with high sensitivity and throughput capacity using a bdelloid rotifer. Ecotoxicol. Environ. Saf. 144, 115–122.CrossRefGoogle Scholar
  24. 24.
    Poeggeler, B., Durand, G., Polidori, A., Pappolla, M. A., Vega-Naredo, I., Coto-Montes, A., Boker, J., Hardeland, R., Pucci, B. (2005) Mitochondrial medicine: neuroprotection and life extension by the new amphiphilic nitrone LPBNAH1 acting as a highly potent antioxidant agent. J. Neurochem. 95, 962–973.CrossRefGoogle Scholar
  25. 25.
    Rico-Martínez, R., Arzate-Cárdenas, M. A., Robles-Vargas, D., Pérez-Legaspi, I. A., Alvarado-Flores, J., Santos-Medrano, G. E. (2016) Rotifers as models in toxicity screening of chemicals and environmental samples. In: Larramendy, M. L., Soloneski, S. (eds) Invertebrates - Experimental Models in Toxicity Screening. In Tech; pp. 57–99.Google Scholar
  26. 26.
    Singhuber, J., Zhu, M., Prinz, S., Kopp, B. (2009) Aconitum in Traditional Chinese Medicine - A valuable drug or an unpredictable risk? J. Ethnopharmacol. 126, 18–30.CrossRefGoogle Scholar
  27. 27.
    Snell, T. W., Persoone, G. (1989) Acute toxicity bioassays using rotifers. I. A test for brackish and marine environments with Brachionus plicatilis. Aquat. Toxicol. 14, 65–80.CrossRefGoogle Scholar
  28. 28.
    Tai, C. J., El-Shazly, M., Wu, T. Y., Wu, T. Y., Lee, K. T., Csupor, D., Hohmann, J., Chang, F. R., Wu, Y. C. (2015) Clinical aspects of Aconitum preparations. Planta Med. 81, 1017–1028.CrossRefGoogle Scholar
  29. 29.
    Wada, K., Ohkoshi, E., Zhao, Y., Goto, M., Morris-Natschke, S. L., Lee, K. H. (2015) Evaluation of Aconitum diterpenoid alkaloids as antiproliferative agents. Bioorg. Med. Chem. Lett. 25, 1525–1531.CrossRefGoogle Scholar
  30. 30.
    Wang, J. L., Shen, X. L., Chen, Q. H., Qi, G., Wang, W., Wang, F. P. (2009) Structure-analgesic activity relationship studies on the C18- and C19-diterpenoid alkaloids. Chem. Pharm. Bull. 57, 801–807.CrossRefGoogle Scholar
  31. 31.
    Yunusov, M. S. (2011) Antiarrhythmic agents based on diterpenoid alkaloids. Russ. Chem. Bull. 60, 633–638.CrossRefGoogle Scholar
  32. 32.
    Zhao, X. Y., Wang, Y., Li, Y., Chen, X. Q., Yang, H., Yue, J. M., Hu, G. Y. (2003) Songorine, a diterpenoid alkaloid of the genus Aconitum, is a novel GABAA receptor antagonist in rat brain. Neurosci. Lett. 337, 33–36.CrossRefGoogle Scholar
  33. 33.
    Zyuz’kov, G. N., Krapivin, A. V., Nesterova, Y. V., Povetieva, T. N., Zhdanov, V. V., Suslov, N. I., Fomina, T. I., Udut, E. V., Miroshnichenko, L. A., Simanina, E. V., Semenov, A. A., Kravtsova, S., Dygai, A. M. (2012) Mechanisms of regeneratory effects of Baikal Aconite diterpene alkaloids. Bull. Exp. Biol. Med. 153, 847–851.CrossRefGoogle Scholar
  34. 34.
    Zyuz’kov, G. N., Povet’eva, T. N., Semenov, A. A., Zhdanov, V. V., Krapivin, A. V., Nesterova, Y. V., Suslov, N. I., Fomina, T. I., Dygai, A. M. (2013) Napelline as wound-healing medication. Russ., (RU2475259C1): 8 pp.Google Scholar

Copyright information

© Akadémiai Kiadó, Budapest 2017

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

Authors and Affiliations

  1. 1.Faculty of Pharmacy, Department of PharmacognosyUniversity of SzegedSzegedHungary
  2. 2.Interdisciplinary Centre for Natural ProductsUniversity of SzegedSzegedHungary
  3. 3.Faculty of Medicine, Department of PsychiatryUniversity of SzegedSzegedHungary

Personalised recommendations