Research Article
Volume 4 Issue 10 - 2020
Evaluation of Aerial Parts of Echium angustifolium on Ciguatoxins toxicity Using Molecular Modelling and Albino Mice models
Inass A Sadawe1, Amira A Gbaj2, Abdelraouf O Algheryane3, Nisreen H Meiqal1, Salah M Bensaber1, Abdulathim A A Alshoushan4, Halima A Gbaj1, Massaud Salem Maamar5, Anton Hermann6 and Abdul M Gbaj1*
1Department of Medicinal Chemistry, Faculty of Pharmacy, University of Tripoli, Libya
2Novelien School, Tripoli Centre, Tripoli, Libya
3National Commission for DNA Research and Analysis, Libya
4Food and Drug Control Centre (LFDA), Tripoli, Libya
5Zoology Department, Faculty of Science, Tripoli University, Libya
6Department of Biosciences, University of Salzburg, Salzburg, Austria
*Corresponding Author: Abdul M Gbaj, Professor of Genetics and Biochemistry, Department of Medicinal Chemistry, Faculty of Pharmacy, University of Tripoli, Libya.
Received: August 15, 2020; Published: September 28, 2020


Ciguatoxin (CTX) is a polyether neurotoxin compound produced by microalgae (dinoflagellate, Gambierdiscus spp). The toxin is accumulated and transformed throughout the sea food chain causing many life-threatening neurological problems in Libya and other Mediterranean and North African countries and eventually may cause death.

The plant species Echium angustifolium which is locally known as “Hannet Al-Aggrab” contains pyrrolizidine alkaloids, phenolic acid derivatives, flavonoids and other constituents that are known for their numerous biological activities. For treatments of ciguatera fish poisoning the plant has not been studied so far in the Mediterranean and North Africa regions. In the present study, Echium angustifolium aqueous extract was evaluated for its ability to reduce or revoke the effect of ciguatoxins in mice. Molecular docking and in vivo animal studies were performed in order to determine the potential effect of Echium angustifolium aqueous extract against ciguatoxicity. The content of Echium angustifolium extract was evaluated using molecular modelling against ciguatoxin on sodium (Na+) and potassium (K+) voltage-gated channels. Hesperetin was found the most active compounds with a Gibbs energy of -8.5 Kcal/mol. For K+ voltage-gated channels was ellagic acid which was the most active compounds with a Gibbs energy of -9.0 Kcal/mol. Our results revealed that Echium angustifolium constituents form hydrogen bonds with active sites of Na+ and K+ channels and protect the mice from ciguatoxin toxicity. We propose that Echium angustifolium constituents can be used to prevent ciguatoxin toxicity. Further chemical synthesis of analogues and in vivo studies will be necessary to substantiate the obtained results.

Keywords: Ciguatera Fish Poisoning; Ciguatoxin; Neurotoxin; Molecular Modelling, Na+, K+ Channels


  1. Parsons ML., et al. “An examination of the epiphytic nature of Gambierdiscus toxicus, a dinoflagellate involved in ciguatera fish poisoning”. Harmful Algae 10 (2011): 598-605.
  2. Nishimura T., et al. “Genetic Diversity and Distribution of the Ciguatera-Causing Dinoflagellate Gambierdiscus (Dinophyceae) in Coastal Areas of Japan”. PLoS One 8 (2013).
  3. Rhodes LL., et al. “Ciguatera Fish Poisoning: The Risk from an Aotearoa/New Zealand Perspective”. Toxins (2020): 12.
  4. Grant IC. “Ichthyosarcotoxism: poisoning by edible fish”. Journal of Accident and Emergency Medicine 14 (1997): 246-251.
  5. Bagnis R., et al. “Problems of toxicants in marine food products: 1. Marine biotoxins”. Bulletin of the World Health Organization 42 (1970): 69-88.
  6. Halstead BW. “Poisonous fishes”. Public Health Reports 73 (1958): 302-312.
  7. Lewis RJ., et al. “Rapid Extraction and Identification of Maitotoxin and Ciguatoxin-Like Toxins from Caribbean and Pacific Gambierdiscus Using a New Functional Bioassay”. PLoS One 11 (2016).
  8. Boente-Juncal A., et al. “Structure Elucidation and Biological Evaluation of Maitotoxin-3, a Homologue of Gambierone, from Gambierdiscus belizeanus”. Toxins 11 (2019).
  9. Pisapia F., et al. “Maitotoxin-4, a Novel MTX Analog Produced by Gambierdiscus excentricus”. Marine Drugs 15 (2017).
  10. Wang DZ. “Neurotoxins from Marine Dinoflagellates: A Brief Review”. Marine Drugs 6 (2008): 349-371.
  11. Larsson ME., et al. “Toxicology of Gambierdiscus (Dinophyceae) from Tropical and Temperate Australian Waters”. Marine Drugs 16 (2018): 7.
  12. Pisapia F., et al. “Maitotoxin-4, a Novel MTX Analog Produced by Gambierdiscus excentricus”. Marine Drugs 15 (2017).
  13. Gatti CM., et al.Tectus niloticus (Tegulidae, Gastropod) as a Novel Vector of Ciguatera Poisoning: Clinical Characterization and Follow-Up of a Mass Poisoning Event in Nuku Hiva Island (French Polynesia)”. Toxins 10 (2018).
  14. Friedman MA., et al. “Ciguatera Fish Poisoning: Treatment, Prevention and Management”. Marine Drugs 6 (2008): 456-479.
  15. Friedman MA., et al. “An Updated Review of Ciguatera Fish Poisoning: Clinical, Epidemiological, Environmental, and Public Health Management”. Marine Drugs 15 (2017).
  16. Campora CE., et al. “Detection of ciguatoxin in fish tissue using sandwich ELISA and neuroblastoma cell bioassay”. Journal of Clinical Laboratory Analysis 22 (2008): 246-253.
  17. Yamaoka K., et al. “A quantitative and comparative study of the effects of a synthetic ciguatoxin CTX3C on the kinetic properties of voltage-dependent sodium channels”. British Journal of Pharmacology 142 (2004): 879-889.
  18. Gilchrist J., et al. “Animal Toxins Influence Voltage-Gated Sodium Channel Function”. Handbook of Experimental Pharmacology 221 (2014): 203-229.
  19. Mor-Mussery A., et al. “New methodology for quantifying the effects of perennials on their patch productivity in semi-arid environments”. Environmental Management 55 (2015): 1139-1146.
  20. El Rokh AR., et al. “Sucrose diester of aryldihydronaphthalene-type lignans from Echium angustifolium Mill. and their antitumor activity”. Phytochemistry 149 (2018): 155-160.
  21. Silver KS., et al. “Voltage-Gated Sodium Channels as Insecticide Targets”. Advances in Insect Physiology 46 (2014): 389-433.
  22. Dong K., et al. “Molecular Biology of Insect Sodium Channels and Pyrethroid Resistance”. Insect Biochemistry and Molecular Biology 50 (2014): 1-17.
  23. Tiwari R., et al. “Carborane clusters in computational drug design: a comparative docking evaluation using AutoDock, FlexX, Glide, and Surflex”. Journal of Chemical Information and Modeling 49 (2009): 1581-1589.
  24. Marrelli M., et al. “A Review of Biologically Active Natural Products from Mediterranean Wild Edible Plants: Benefits in the Treatment of Obesity and Its Related Disorders”. Molecules 25 (2020).
  25. Geraci A., et al. “The wild taxa utilized as vegetables in Sicily (Italy): a traditional component of the Mediterranean diet”. Journal of Ethnobiology and Ethnomedicine 14 (2018).
  26. Banerjee P., et al. “ProTox-II: a webserver for the prediction of toxicity of chemicals”. Nucleic Acids Research 46 (2018): W257-W263.
  27. Daina A., et al. “SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules”. Scientific Reports 7 (2017): 42717-42730.
  28. Rossi F., et al. “Protective effect of Heliotropium foertherianum (Boraginaceae) folk remedy and its active compound, rosmarinic acid, against a Pacific ciguatoxin”. Journal of Ethnopharmacology 143 (2012): 33-40.
  29. Bellassoued K., et al. “Seasonal variation of Sarpa salpa fish toxicity, as related to phytoplankton consumption, accumulation of heavy metals, lipids peroxidation level in fish tissues and toxicity upon mice”. Environmental Monitoring and Assessment 185 (2013): 1137-1150.
  30. Bellassoued K., et al. “Neurotoxicity in rats induced by the poisonous dreamfish (Sarpa salpa)”. Pharmaceutical Biology 53 (2015): 286-295.
  31. Pan X., et al. “Structure of the human voltage-gated sodium channel Na(v)1.4 in complex with β1”. Science 362 (2018).
  32. Doyle DA., et al. “The structure of the potassium channel: molecular basis of K+ conduction and selectivity”. Science 280 (1998): 69-77.
  33. Inserra MC., et al. “Multiple sodium channel isoforms mediate the pathological effects of Pacific ciguatoxin-1”. Scientific Reports 7 (2017): 42810.
  34. Touska F., et al. “Ciguatoxins Evoke Potent CGRP Release by Activation of Voltage-Gated Sodium Channel Subtypes Na(V)1.9, Na(V)1.7 and Na(V)1.1”. Marine Drugs 15 (2017).
  35. Chen L., et al. “The modulation of voltage-gated potassium channels by anisotonicity in trigeminal ganglion neurons”. Neuroscience 154 (2008): 482-495.
  36. Holt PA., et al. “Molecular docking of intercalators and groove-binders to nucleic acids using Autodock and Surflex”. Journal of Chemical Information and Modeling 48 (2008): 1602-1615.
  37. Gilad Y and Senderowitz H. “Docking studies on DNA intercalators”. Journal of Chemical Information and Modeling 54 (2014): 96-107.
  38. Robertson J and Stevens K. “Pyrrolizidine alkaloids: occurrence, biology, and chemical synthesis”. Natural Product Reports 34 (2017): 62-89.
  39. Luckert C., et al. “PXR: Structure-specific activation by hepatotoxic pyrrolizidine alkaloids”. Chemico-Biological Interactions 288 (2018): 38-48.
  40. Chagas CM., et al. “Drug metabolites and their effects on the development of adverse reactions: Revisiting Lipinski's Rule of Five”. International Journal of Pharmaceutics 549 (2018): 133-149.
Citation: Abdul M Gbaj., et al. “Evaluation of Aerial Parts of Echium angustifolium on Ciguatoxins toxicity Using Molecular Modelling and Albino Mice models”. EC Emergency Medicine and Critical Care 4.10 (2020): 97-111.

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