Repurposing drugs to treat trichinellosis: in vitro analysis of the anthelmintic activity of nifedipine and Chrysanthemum coronarium extract

Abstract

Albendazole is the most common benzimidazole derivative used for trichinellosis treatment but has many drawbacks. The quest for alternative compounds is, therefore, a target for researchers. This work aims to assess the in vitro anthelmintic effect of nifedipine, a calcium channel blocker, and a methanol extract of the flowers of Chrysanthemum coronarium as therapeutic repurposed drugs for treating different developmental stages of Trichinella spiralis in comparison with the reference drug, albendazole. Adult worms and muscle larvae of Trichinella spiralis were incubated with different concentrations of the studied drugs. Drug effects were evaluated by parasitological and electron microscopic examination.

As a result, the effects of these drugs on muscle larvae were time and dose-dependent. Moreover, the LC₅₀ after 48 h incubation was 81.25 µg/ml for albendazole, 1.24 µg/ml for nifedipine, and 229.48 µg/ml for C. coronarium. Also, the effects of the tested drugs were prominent on adult worms as the LC₅₀ was 89.77 µg/ml for albendazole, 1.87 µg/ml for nifedipine, and 124.66 µg/ml for C. coronarium. SEM examination of the tegument of T. spiralis adult worms and larvae showed destruction of the adult worms' tegument in all treated groups. The tegument morphological changes were in the form of marked swellings or whole body collapse with the disappearance of internal contents. Furthermore, in silico studies showed that nifedipine might act as a T. spiralis β-tubulin polymerization inhibitor.

Our results suggest that nifedipine and C. coronarium extract may be useful therapeutic agents for treating trichinellosis and warrant further assessment in animal disease models.