Abstract

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

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