Inhibitory Potential of Ferula assafoetida Extract on L-type Calcium Channel Protein Revealed by Zebrafish Studies and Molecular Docking

Abstract

Ferula assafoetida is a part of many herbal formulations and hence it is pertinent to check the safety of its components specially to growing embryos. Zebrafish (Danio rerio) is considered to be one of the best models to study human embryonic development and metabolic pathways as its genome is fully sequenced and it possesses easily detectable developmental properties. In present study, the embryos of Danio rerio were treated with different concentrations of methanolic extract of Ferula assafoetida (MEFA) and its effects were checked at different post fertilization periods. Decreased heart beat rates, shrinkage of the chorion wall and other developmental abnormalities leading to the death of the embryos were observed. The methanolic extract of Ferula assafoetida was subjected to GC-MS to determine the different compounds present. Cardiotoxicity of these compounds were studied as it is one of the important factors for the retraction of a drug from the market. Molecular docking studies with L-type calcium channel (LTCC), a protein important for cardiac functioning, showed strong binding to the phytochemicals in the extract, with the maximum binding affinity observed with 26-hydroxycholesterol. The study proves that the methanolic extract of Ferula assafoetida contains phytochemicals which have the potential to cause cardiotoxicity in zebrafish embryos by interfering with the functions of LTCC possibly leading to arrhythmia. Altogether, our data suggest that the usage of these extracts in drug formulations should be done with caution. This is also indicative of the possible cytotoxic effect of the extract which could be tapped in the search for anticancer drugs.