Anthelmintic Activity of Yeast Particle-Encapsulated Terpenes

Soil-transmitted nematodes (STN) infect 1–2 billion of the poorest people worldwide. Only benzimidazoles are currently used in mass drug administration, with many instances of reduced activity. Terpenes are a class of compounds with anthelmintic activity. Thymol, a natural monoterpene phenol, was us...

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Main Authors: Zeynep Mirza, Ernesto R. Soto, Yan Hu, Thanh-Thanh Nguyen, David Koch, Raffi V. Aroian, Gary R. Ostroff
Format: Article
Language:English
Published: MDPI AG 2020-06-01
Series:Molecules
Subjects:
Online Access:https://www.mdpi.com/1420-3049/25/13/2958
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author Zeynep Mirza
Ernesto R. Soto
Yan Hu
Thanh-Thanh Nguyen
David Koch
Raffi V. Aroian
Gary R. Ostroff
author_facet Zeynep Mirza
Ernesto R. Soto
Yan Hu
Thanh-Thanh Nguyen
David Koch
Raffi V. Aroian
Gary R. Ostroff
author_sort Zeynep Mirza
collection DOAJ
description Soil-transmitted nematodes (STN) infect 1–2 billion of the poorest people worldwide. Only benzimidazoles are currently used in mass drug administration, with many instances of reduced activity. Terpenes are a class of compounds with anthelmintic activity. Thymol, a natural monoterpene phenol, was used to help eradicate hookworms in the U.S. South circa 1910. However, the use of terpenes as anthelmintics was discontinued because of adverse side effects associated with high doses and premature stomach absorption. Furthermore, the dose–response activity of specific terpenes against STNs has been understudied. Here we used hollow, porous yeast particles (YPs) to efficiently encapsulate (>95%) high levels of terpenes (52% <i>w/w</i>) and evaluated their anthelmintic activity on hookworms (<i>Ancylostoma ceylanicum)</i>, a rodent parasite (<i>Nippostrongylus brasiliensis</i>), and whipworm (<i>Trichuris muris)</i>. We identified YP–terpenes that were effective against all three parasites. Further, YP–terpenes overcame albendazole-resistant <i>Caenorhabditis elegans</i>. These results demonstrate that terpenes are broad-acting anthelmintics. Terpenes are predicted to be extremely difficult for parasites to resist, and YP encapsulation provides water-suspendable terpene materials without surfactants and sustained terpene release that could lead to the development of formulations for oral delivery that overcome fast absorption in the stomach, thus reducing dosage and toxic side effects.
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spelling doaj.art-f00ada8b43e44e58bf36077988f407f52023-11-20T05:07:49ZengMDPI AGMolecules1420-30492020-06-012513295810.3390/molecules25132958Anthelmintic Activity of Yeast Particle-Encapsulated TerpenesZeynep Mirza0Ernesto R. Soto1Yan Hu2Thanh-Thanh Nguyen3David Koch4Raffi V. Aroian5Gary R. Ostroff6Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USASoil-transmitted nematodes (STN) infect 1–2 billion of the poorest people worldwide. Only benzimidazoles are currently used in mass drug administration, with many instances of reduced activity. Terpenes are a class of compounds with anthelmintic activity. Thymol, a natural monoterpene phenol, was used to help eradicate hookworms in the U.S. South circa 1910. However, the use of terpenes as anthelmintics was discontinued because of adverse side effects associated with high doses and premature stomach absorption. Furthermore, the dose–response activity of specific terpenes against STNs has been understudied. Here we used hollow, porous yeast particles (YPs) to efficiently encapsulate (>95%) high levels of terpenes (52% <i>w/w</i>) and evaluated their anthelmintic activity on hookworms (<i>Ancylostoma ceylanicum)</i>, a rodent parasite (<i>Nippostrongylus brasiliensis</i>), and whipworm (<i>Trichuris muris)</i>. We identified YP–terpenes that were effective against all three parasites. Further, YP–terpenes overcame albendazole-resistant <i>Caenorhabditis elegans</i>. These results demonstrate that terpenes are broad-acting anthelmintics. Terpenes are predicted to be extremely difficult for parasites to resist, and YP encapsulation provides water-suspendable terpene materials without surfactants and sustained terpene release that could lead to the development of formulations for oral delivery that overcome fast absorption in the stomach, thus reducing dosage and toxic side effects.https://www.mdpi.com/1420-3049/25/13/2958terpenesessential oilsyeast particlesanthelmintichookwormwhipworm
spellingShingle Zeynep Mirza
Ernesto R. Soto
Yan Hu
Thanh-Thanh Nguyen
David Koch
Raffi V. Aroian
Gary R. Ostroff
Anthelmintic Activity of Yeast Particle-Encapsulated Terpenes
Molecules
terpenes
essential oils
yeast particles
anthelmintic
hookworm
whipworm
title Anthelmintic Activity of Yeast Particle-Encapsulated Terpenes
title_full Anthelmintic Activity of Yeast Particle-Encapsulated Terpenes
title_fullStr Anthelmintic Activity of Yeast Particle-Encapsulated Terpenes
title_full_unstemmed Anthelmintic Activity of Yeast Particle-Encapsulated Terpenes
title_short Anthelmintic Activity of Yeast Particle-Encapsulated Terpenes
title_sort anthelmintic activity of yeast particle encapsulated terpenes
topic terpenes
essential oils
yeast particles
anthelmintic
hookworm
whipworm
url https://www.mdpi.com/1420-3049/25/13/2958
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