Antiparasitic Effects and Cellular Mechanisms of Formononetin (a Natural Isoflavone) Against Hydatid Cyst Protoscoleces

Background: The chemical agents applied to reduce the complications of hydatid cyst surgery are not free of side effects. For-mononetin (FMN), as a natural isoflavone, has been shown to have various therapeutic benefits. Objectives: We studied the in vitro and ex vivo protoscolicidal activity and cellular mechanisms of FMN against hydatid cyst proto-scoleces. Methods: Formononetin at 75,150, and 300 mu g/mL was mixed with hydatid cyst protoscoleces (103/mL), and the viability was de-termined in 5 to 60 min through eosin staining assay. The effect of FMN on caspase-3 activity was tested through a commercial colorimetric protease kit. In addition, the penetrability of the plasma membrane of protoscoleces after exposure to FMN was also determined by the SYTOX assay. Results: Formononetin at 300 mu g/mL completely destroyed hydatid cyst protoscoleces after 30 minutes. While at 150 mu g/mL, after 60 minutes of contact, 100% of protoscoleces were eliminated. By ex vivo assay, FMN showed its antiparasitic effect for longer peri-ods. Based on these results, FMN at 300 mu g/mL concentration completely eliminated hydatid cyst protoscoleces after 60 minutes of exposure. While at a concentration of 150 mu g/mL after 60 minutes, 89.6% of protoscoleces were destroyed. Formononetin noticeably increased (P < 0.001) the activity of caspase-3 and the permeability of protoscoleces dose-dependently. Conclusions: Formononetin as a natural product showed promising effects on the protoscoleces of hydatid cysts, indicating that it can be considered a valuable scolicidal agent. However, additional investigations are necessary to evaluate its efficacy in animal models and human subjects.

Automated summary

The natural isoflavone FMN has shown promising effects on protoscolices of hydatid cysts by increasing caspase-3 activity and cell membrane permeability. FMN can completely eliminate protoscolices at a certain concentration, indicating its potential as a valuable scolicidal agent. Further investigations are needed to evaluate its efficacy in animal models and human subjects.