Background Cystic echinococcosis caused by the cestode Echinococcus granulosus remains a serious helminthic zoonosis affecting humans and animals in many endemic developing countries. Surgical intervention is the best management choice, although it is associated with high recurrence rates and serious complications. Also, the commonly used chemotherapeutics exhibited serious side effects. This study aimed to evaluate the protoscolicidal effects of eugenol (Eug) essential oil and its nanoemulsion (Eug-NE) against protoscoleces (PCs) of hydatid cysts in vitro. Methods Eug-NE was prepared and characterized. Their cytotoxicity on macrophages was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. E. granulosus PCs were treated with various concentrations of Eug and Eug-NE at different exposure times. The viability of protoscoleces was evaluated by the eosin exclusion test, and the changes in the morphology of protoscoleces were assessed. Albendazole (ABZ) was used as a positive control. Results The cellular cytotoxicity of Eug and Eug-NE on macrophage cells, in minimum and maximum concentrations (0.2 and 1 μl/mL), were nearly negligible ranging from 4.7% to 8.3% and 3.7% to 7.2%, respectively. The results showed highly significant activity of Eug-NE and Eug against hydatid PCs compared to ABZ (P < 0.05). Eug and Eug-NE have similar protoscolicidal effects at all used concentrations. Their highest scolicidal activity (100% mortality rate) was recorded at 1 μl/ml after 30 min incubation (LC50 = 0.298—LC90 = 0.521 and LC50 = 0.309—LC90 = 0.646, respectively). Both formulations showed time- and dose-dependent effects. Conclusions This study suggested the potent scolicidal activities of Eug and Eug-NE as promising alternative scolicidal agents. Future studies are recommended to explore the mechanism of action and treatment response in vivo and clinical settings.

Conventional scolicidal agents are still unsatisfactory in combating hydatid disease due to their low efficacy and increased drug side effects. Therefore, novel scolicides are required. This study aimed to evaluate the antihydatic and immunomodulatory effects of eugenol essential oil (Eug) and its nanoemulsion (Eug-NE) in cystic echinococcosis (CE). Eug and Eug-NE were administered orally to CE-infected rats and compared to albendazole (ABZ). Hydatid cyst development was assessed based on organ weight and hypertrophy indicators of the infected organs, along with a histopathological and histochemical evaluation of collagen content. The immunomodulatory effects of treatment on CE were evaluated by serum cytokine levels measurement of interferon-γ (IFN-γ) and interleukin (IL)-4 and immunohistochemical (IHC) analysis of signal transducer and activator of transcription 4 (STAT4) and GATA-binding protein 3 (GATA3) markers. Eug-NE was the most effective in reducing the cyst weights, organ weights, and hypertrophy indicators and improving histopathological lesions with reduced collagen content. Eug and Eug-NE significantly increased the IFN-γ levels and decreased the IL-4 levels, while IHC analysis demonstrated a significant reduction in STAT4 and GATA3 expression in all treated groups. Eug and Eug-NE demonstrated antihydatic and preventative effects, with a substantial decrease in liver fibrosis compared to that of ABZ. Besides their promising immunomodulatory effects, their good treatment response suggests their use as alternatives or complementary scolicidal agents in hydatid cyst treatment.