Ellagic acid shows early promise in treating piroplasmosis

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Protozoa that cause piroplasmosis. Photo: Centers for Disease Control/ Steven Glenn (Public domain)

Nanoparticles loaded with ellagic acid have potential in fighting a hard-to-treat protozoal infection in horses and other animals, the findings of research suggest.

There are no effective vaccines against Babesia and Theileria parasites, which cause piroplasmosis in livestock.

Treatment options are limited, depending heavily on antiprotozoal drugs.

Some jurisdictions require euthanasia of infected animals because of the risk of the blood-borne parasites being spread by biting insects.

Researchers Amani Magdy Beshbishy, Gaber El-Saber Batiha, Naoaki Yokoyama and Ikuo Igarashi, writing in the journal Parasites & Vectors, say the need for new antiprotozoal agents is becoming increasingly urgent.

At present, diminazene aceturate and imidocarb dipropionate are the only options for treating piroplasmosis in horses and cattle. However, there are several challenges with their use, including toxicity, the risk of drug-resistant parasites, drug residues and withdrawal issues.

Neither is approved for treating the parasites in humans, with a combination of atovaquone with azithromycin used due to their low side-effects.

The study team, with the National Research Center for Protozoan Diseases at Obihiro University of Agriculture and Veterinary Medicine, focused their work on ellagic acid, a naturally occurring broad-spectrum antioxidant.

It is found in grapes, strawberries, blackcurrants, raspberries, green tea and many herbal plants.

It has potent preventive and therapeutic effects against a range of cancers. It has also been found to possesses anti-inflammatory properties.

Recently, it was found to have antimalarial properties and has shown some potential against the agent that causes leishmaniasis.

Despite its medicinal properties, ellagic acid has poor bioavailability. It is not easily soluble in water and is easily oxidized by heat. It also has a short plasma half-life because, when given orally, it is affected by intestinal microorganisms and rapidly eliminated from the body.

The study team thought that loading ellagic acid into slow-release nanoparticles could solve these problems.

Nanoparticles, they said, are considered to be the most promising delivery system for compounds with low bioavailability.

They created two types of nanoparticles loaded with ellagic acid for their study.

They then tested their effectiveness in a laboratory setting against the growth of Babesia bovis, Babesia bigemina, Babesia divergens, Babesia caballi and Theileria equi, which cause piroplasmosis in a range of animals.

They also investigated the effect of a combination treatment with the current drugs used to treat these protozoan infections.

They found that ellagic acid acted against the protozoa. Combination treatments also showed promise. The findings, they said, supported the use of nanoparticles as an alternative antiparasitic agent.

Discussing their findings, the authors said that while previous reports had documented ellagic acid’s strong inhibition of the growth of many protozoan parasites, its mode of action has yet to be fully understood.

They said ellagic acid or its microspheres and combinations with diminazene aceturate might be used as a novel regime for treating piroplasmosis in a wide range of animals.

“Furthermore, elagic acid or its microspheres and atovaquone or clofazimine combinations could be used as an option for treating human babesiosis.”

They said a viability test would be required to detect whether the effect of ellagic acid or the nanoparticles resulted in inhibition of growth or death of the parasites in future studies.

Conclusively, they said, ellagic-acid-loaded nanoparticles are a promising route for promoting the bioavailability and solubility of the powerful natural antioxidant, while improving and sustaining its effectiveness against the protozoa.

Ellagic acid microspheres restrict the growth of Babesia and Theileria in vitro and Babesia microti in vivo
Amani Magdy Beshbishy, Gaber El-Saber Batiha, Naoaki Yoko yama and Ikuo Igarashi
Parasites & Vectors 2019 12:269 https://doi.org/10.1186/s13071-019-3520-x

The study, published under a Creative Commons License, can be read here

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