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

Dastyar Haghigh, etareh and Mahmoudvand, Hossein and Khudair Khalaf, Amal and Adineh, Ahmad and Maleki, Ali Mohammad and Ghasemian Yadegari, Javad (2023) Antiparasitic Effects and Cellular Mechanisms of Formononetin (a Natural Isoflavone) Against Hydatid Cyst Protoscoleces. Jundishapur Journal of Natural Pharmaceutical Products.

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Abstract

Background: The chemical agents applied to reduce the complications of hydatid cyst surgery are not free of side effects. Formononetin (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 protoscoleces. Methods: Formononetin at 75, 150, and 300 μg/mL was mixed with hydatid cyst protoscoleces (103/mL), and the viability was determined 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 μg/mL completely destroyed hydatid cyst protoscoleces after 30 minutes. While at 150 μg/mL, after 60 minutes of contact, 100% of protoscoleces were eliminated. By ex vivo assay, FMN showed its antiparasitic effect for longer periods. Based on these results, FMN at 300 μg/mL concentration completely eliminated hydatid cyst protoscoleces after 60 minutes of exposure. While at a concentration of 150 μg/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.

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