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青蒿粉混悬剂的体内抗疟功效。

In vivo antimalarial efficacy of Artemisia afra powder suspensions.

机构信息

Parasite Chemotherapy Unit, Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4123 Allschwil, Switzerland; University of Basel, 4001 Basel, Switzerland.

Parasite Chemotherapy Unit, Department of Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, 4123 Allschwil, Switzerland; Division of Clinical Pharmacology and Toxicology, Department of Biomedicine, University Hospital Basel, 4031 Basel, Switzerland.

出版信息

Phytomedicine. 2024 Jul;129:155644. doi: 10.1016/j.phymed.2024.155644. Epub 2024 May 18.

Abstract

BACKGROUND

A global death toll of 608,000 in 2022 and emerging parasite resistance to artemisinin, the mainstay of antimalarial chemotherapy derived from the Chinese herb Artemisia annua, urge the development of novel antimalarials. A clinical trial has found high antimalarial potency for aqueous extracts of A. annua as well as its African counterpart Artemisia afra, which contains only trace amounts of artemisinin. The artemisinin-independent antimalarial activity of A. afra points to the existence of other antimalarials present in the plant. However, the publication was retracted due to ethical and methodological concerns in the trial, so the only evidence for antimalarial activity of A. afra is built on in vitro studies reporting efficacy only in the microgram per milliliter range.

HYPOTHESIS

Our study aims to shed more light on the controversy around the antimalarial activity of A. afra by assessing its efficacy in mice. In particular, we are testing the hypothesis that A. afra contains a pro-drug that is inactive in vitro but active in vivo after metabolization by the mammalian host.

METHODS

Plasmodium berghei-infected mice were treated once or thrice (on three consecutive days) with various doses of A. afra, A. annua, or pure artemisinin.

RESULTS

Aqueous powder suspensions of A. annua but not A. afra showed antimalarial activity in mice.

CONCLUSION

Our experiments conducted in mice do not support the pro-drug hypothesis.

摘要

背景

2022 年全球死亡人数达到 60.8 万,寄生虫对青蒿素的抗药性不断出现,青蒿素是从中国草药青蒿中提取的抗疟化疗药物的主要成分,迫切需要开发新型抗疟药物。一项临床试验发现,青蒿和其非洲对应物青蒿素的水提物具有很高的抗疟活性,而青蒿素只含有微量的青蒿素。青蒿素的抗疟活性表明该植物中还存在其他抗疟成分。然而,由于试验中的伦理和方法学问题,该出版物被撤回,因此,青蒿素抗疟活性的唯一证据是基于体外研究报告的仅在微克/毫升范围内有效的研究结果。

假设

我们的研究旨在通过评估青蒿素在小鼠中的疗效来进一步阐明青蒿素抗疟活性的争议。具体来说,我们正在检验一个假设,即青蒿素含有一种前药,在体外无活性,但在哺乳动物宿主代谢后具有活性。

方法

用不同剂量的青蒿素、青蒿或纯青蒿素对感染疟原虫的小鼠进行一次或三次(连续三天)治疗。

结果

青蒿素的水提粉混悬剂在小鼠中具有抗疟活性,但青蒿素的水提粉混悬剂没有。

结论

我们在小鼠中进行的实验不支持前药假说。

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