Medicinal plants with scolicidal activity against Echinococcus granulosus protoscolices: A review

The surgery is the standard treatment for hydatid cyst caused by Echinococcus granulosus . One of the bad sequelae of the surgery of hydatid disease is the spillage of the contents of the cyst containing protoscolices. Many scolicidal chemicals such as cetrimide, povidone iodine, hypertonic saline and silver nitrate were injected into the cyst to kill the protoscolices before cyst removal. As a result of development of resistance and side effects of chemical scolicidals, alternative drugs with minimal adverse effects are still required. Our review focused on plants with scolicidal effects, to encourage the clinical trials to determine their in vivo and clinical effictiveness, the active ingredients, the mode of action, and toxicity.


Introduction
Hydatid disease caused by Echinococcus granulosus, was the most common parasitic diseases, in animals and humans.Hydatid cysts can be occurred in different host organs which may lead to death.The benefit of protoscolicidal chemicals that they are injected into hydatid cysts prior to surgical removal of the cyst, to kill protoscolices and thus eliminating the spillage of viable protoscolices and development of secondary hydatid cysts (1) .
Different scolicidal chemicals such as cetrimide, povidone iodine, hypertonic saline and silver nitrate were used for hydatid cysts sterilization.However, the scolicidal required long exposure time to kill the protoscolices is not suitable for PAIR technique of hydatid cyst (puncture, aspiration, injection of scolicidal, reaspiration) during surgery.As a result of development of resistance and side effects of chemical scolicidals, alternative drugs with minimal adverse effects are still required (2)(3) .
In this review, Scopus, Google scholar, Pub Med, Web of Science, Science Direct and EBSCO, were searched for medicinal plants with protoscolicidal effects.The current review focused on the plants with scolicidal activity, to encourage the clinical trials to determine their in vivo and clinical effectiveness, the active ingredients, the mode of action, and toxicity.

Capparis spinosa
The extract of Capparis spinosa at concentration of at 300 and 600 mg/ml, possessed potent in vitro protoscolicidal effects, it kill all the protoscolices within 10 and 5 min, respectively (11)(12) .

Citrus medica
The aqueous extract of the Citrus medica fruits (90 mg/ml) killed all the protoscolices after 4 days of incubation (14)(15) .

Nectaroscordum tripedale
The extract of the leaves of Nectaroscordum tripedale at 100 mg/ml concentration killed all the protoscolices after exposure for 5 min (24) .

Olea europaea
The leaves extract of Olea europaea at 300 mg/ml concentration killed all the scoleces after exposure for 10 min, and at 150 mg/ml it killed all the scoleces after exposure for 20 min.When the leaves extract of Olea europaea at 150 and 300 mg/ml concentrations, injected directly into the cyst, it killed all the scoleces after incubation for 12 and 25 min, respectively (30)(31) .
The aqueous leave extract of Olea europaea at the concentration of 0.1% and 0.01% exerted high protoscolicidal activities within 120 min of exposure (32) .

Prosopis farcta
The crude alkaloids and crude ethanolic extracts of the leaves of Prosopis farcta showed potent scolicidal activity at 37C 0 , more potency was recorded for the crude alkaloids extract in comparison with the ethanolic extract, the crude alkaloid extract showed a potent scolicidal effect with lower concentrations and shorter exposure time (34) .

Quercus infectoria
The extract of Quercus infectoria caused 100% scolicidal effect after 5 min of exposure at 1000 mg/ml concentration, the mortality rate of protoscolices at 500 mg/ml concentration was 100% after 10 min incubation (35) .

Rheum ribes
Rheum ribes extract possessed stronge protoscolicidal effect, the mortality rate of the protoscolices reached 56.3 and 100% at the concentration of 450 and 900 mg/ml, after 10 min exposure, respectively (36) .

Silybum marianum
Silybum marianum alcoholic extract alone possessed 77%, while scolicidal effect, albendazole killed 69% of the protoscolices, at a concentration of 500 μg/ml for 60 min.However, the more potent scolicidal activity was obtained when the alcoholic extract of Silybum marianum was combined with albendazole (79%) (41) .

Conclusion
The current study reviewed the plant extract or chemicals with scolicidal activity, especially these characterized by high protoscolicidal effect in a short exposure time.These natural remedies can be used as alternatives to the chemical scolicidals for their efficacy and suitability for hydatid cyst PAIR technique during surgery, and because of rapid development of resistance and side effects to the chemical scolicidals.

Disclosure of conflict of interest
No conflict of interest to be disclosed.