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酵母颗粒包封萜烯的驱虫活性。

Anthelmintic Activity of Yeast Particle-Encapsulated Terpenes.

机构信息

Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.

Department of Biology, Worcester State University, Worcester, MA 01602, USA.

出版信息

Molecules. 2020 Jun 27;25(13):2958. doi: 10.3390/molecules25132958.

Abstract

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% ) and evaluated their anthelmintic activity on hookworms (, a rodent parasite (), and whipworm (. We identified YP-terpenes that were effective against all three parasites. Further, YP-terpenes overcame albendazole-resistant . 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.

摘要

土壤传播线虫(STN)感染了全球 10 亿到 20 亿最贫困人口。目前仅使用苯并咪唑类药物进行大规模药物治疗,但许多情况下其活性降低。萜类化合物是一类具有驱虫活性的化合物。百里酚,一种天然单萜酚,曾被用于帮助美国南方地区大约在 1910 年消灭钩虫。然而,由于高剂量和过早胃吸收相关的不良反应,萜类化合物已不再被用作驱虫剂。此外,特定萜类化合物对 STN 的剂量反应活性研究不足。在这里,我们使用空心多孔酵母颗粒(YPs)来高效包封(>95%)高水平的萜类化合物(52%),并评估其对钩虫(一种啮齿动物寄生虫()、鞭虫()的驱虫活性。我们发现了对所有三种寄生虫都有效的 YP-萜类化合物。此外,YP-萜类化合物克服了阿苯达唑耐药的。这些结果表明萜类化合物是广谱驱虫剂。预计寄生虫很难对萜类化合物产生抗药性,而 YP 包封提供了水悬浮的萜类化合物材料,无需表面活性剂和持续的萜类化合物释放,这可能导致开发用于口服给药的制剂,以克服胃内快速吸收,从而减少剂量和毒副作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8670/7411854/0fd12db5c999/molecules-25-02958-g001.jpg

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