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姜黄素联合抗疟药治疗查巴迪疟原虫：药物相互作用及其对泛素/蛋白酶体系统的影响

Treatment of Plasmodium chabaudi Parasites with Curcumin in Combination with Antimalarial Drugs: Drug Interactions and Implications on the Ubiquitin/Proteasome System.

作者信息

Neto Zoraima, Machado Marta, Lindeza Ana, do Rosário Virgílio, Gazarini Marcos L, Lopes Dinora

机构信息

Unidade de Parasitologia, Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa, Rua da Junqueira 100, 1349-008 Lisbon, Portugal ; Centro de Malária e Doenças Tropicais (CMDT), Instituto de Higiene e Medicina Tropical (IHMT), Universidade Nova de Lisboa, Rua da Junqueira 100, 1349-008 Lisbon, Portugal.

出版信息

J Parasitol Res. 2013;2013:429736. doi: 10.1155/2013/429736. Epub 2013 Apr 3.

DOI:10.1155/2013/429736
PMID:23691276
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3649349/
Abstract

Antimalarial drug resistance remains a major obstacle in malaria control. Evidence from Southeast Asia shows that resistance to artemisinin combination therapy (ACT) is inevitable. Ethnopharmacological studies have confirmed the efficacy of curcumin against Plasmodium spp. Drug interaction assays between curcumin/piperine/chloroquine and curcumin/piperine/artemisinin combinations and the potential of drug treatment to interfere with the ubiquitin proteasome system (UPS) were analyzed. In vivo efficacy of curcumin was studied in BALB/c mice infected with Plasmodium chabaudi clones resistant to chloroquine and artemisinin, and drug interactions were analyzed by isobolograms. Subtherapeutic doses of curcumin, chloroquine, and artemisinin were administered to mice, and mRNA was collected following treatment for RT-PCR analysis of genes encoding deubiquitylating enzymes (DUBs). Curcumin was found be nontoxic in BALB/c mice. The combination of curcumin/chloroquine/piperine reduced parasitemia to 37% seven days after treatment versus the control group's 65%, and an additive interaction was revealed. Curcumin/piperine/artemisinin combination did not show a favorable drug interaction in this murine model of malaria. Treatment of mice with subtherapeutic doses of the drugs resulted in a transient increase in genes encoding DUBs indicating UPS interference. If curcumin is to join the arsenal of available antimalarial drugs, future studies exploring suitable drug partners would be of interest.

摘要

抗疟药物耐药性仍然是疟疾控制中的一个主要障碍。东南亚的证据表明，对青蒿素联合疗法（ACT）产生耐药性是不可避免的。民族药理学研究已证实姜黄素对疟原虫属具有疗效。分析了姜黄素/胡椒碱/氯喹以及姜黄素/胡椒碱/青蒿素组合之间的药物相互作用试验，以及药物治疗干扰泛素蛋白酶体系统（UPS）的可能性。在感染了对氯喹和青蒿素耐药的查巴迪疟原虫克隆的BALB/c小鼠中研究了姜黄素的体内疗效，并通过等效线图分析了药物相互作用。给小鼠施用亚治疗剂量的姜黄素、氯喹和青蒿素，治疗后收集mRNA用于对编码去泛素化酶（DUBs）的基因进行RT-PCR分析。发现姜黄素对BALB/c小鼠无毒。姜黄素/氯喹/胡椒碱组合在治疗七天后将疟原虫血症降低至37%，而对照组为65%，显示出相加相互作用。在该疟疾小鼠模型中，姜黄素/胡椒碱/青蒿素组合未显示出良好的药物相互作用。用亚治疗剂量的药物治疗小鼠导致编码DUBs的基因短暂增加，表明UPS受到干扰。如果姜黄素要加入现有的抗疟药物库，未来探索合适药物组合的研究将很有意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c48/3649349/d48a100c44c0/JPR2013-429736.010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c48/3649349/75a1484d3aca/JPR2013-429736.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c48/3649349/a523b0eea4f3/JPR2013-429736.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c48/3649349/d48a100c44c0/JPR2013-429736.010.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c48/3649349/347230776d38/JPR2013-429736.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c48/3649349/1d3514f9a05b/JPR2013-429736.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c48/3649349/3eba7ac89f52/JPR2013-429736.007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c48/3649349/9c69e57f161e/JPR2013-429736.008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c48/3649349/a523b0eea4f3/JPR2013-429736.009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7c48/3649349/d48a100c44c0/JPR2013-429736.010.jpg

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