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L. 种子提取物的抗疟活性及小鼠模型中ANKA对其抗性的选择

Antimalarial Activity of L. Seed Extracts and Selection of Resistance in ANKA in a Mouse Model.

作者信息

Udu Rahma, Oyweri Job, Gathirwa Jeremiah

机构信息

Department of Pure and Applied Sciences, School of Applied & Health Sciences, Technical University of Mombasa, P.O. Box 90420-80100, Mombasa, Kenya.

Centre for Traditional Medicine and Drug Research, Kenya Medical Research Institute, P.O. Box 54840-0002, Nairobi, Kenya.

出版信息

J Pathog. 2021 Feb 3;2021:6165950. doi: 10.1155/2021/6165950. eCollection 2021.

Abstract

BACKGROUND

Chemotherapy plays a crucial role in malaria control. However, the main obstacle to treatment has been the rise of parasite resistance to most antimalarial drugs. Artemisinin-based combination therapies (ACTs) remain the most effective antimalarial medicines available today. However, malaria parasite tolerance to ACTs is now increasingly prevalent especially in Southeast Asia presenting the danger of the spread of ACTs resistance to other parts of the world. Consequently, this creates the need for alternative effective antimalarials. Therefore, this study sought out to determine antimalarial potential, safety, and resistance development of the extracts in a mouse model.

METHOD

Methanolic and ethyl acetate extracts were obtained by solvent extraction. The extracts were assayed for acute toxicity . Additionally, the two extracts were evaluated for antimalarial activity against ANKA strain by the 4-day suppressive test at 500, 250, and 125 mg/kg/day. Packed cell volume was evaluated to determine anemia manifestation. Finally, continuous drug pressure experiment at 500 mg/kg and DNA amplification via PCR were conducted. The amplicons underwent through Sanger sequencing.

RESULTS

There was no toxicity realized in the animals at 2000 mg/kg. Importantly, high parasitemia suppression of 75.52% and 75.30% using a dose of 500 mg/kg of methanolic and ethyl acetate extracts, respectively, was noted. The extracts were able to reverse packed cell volume reduction. -resistant phenotype was selected as delayed parasite clearance. However, there was no change in the nucleotide sequences of MDR1 and CRT genes.

CONCLUSION

The results provide room for future exploitation of the plant as an antimalarial.

摘要

背景

化疗在疟疾控制中起着关键作用。然而,治疗的主要障碍一直是疟原虫对大多数抗疟药物产生耐药性。以青蒿素为基础的联合疗法(ACTs)仍然是目前可用的最有效的抗疟药物。然而,疟原虫对ACTs的耐受性现在越来越普遍,特别是在东南亚,这存在ACTs耐药性传播到世界其他地区的危险。因此,这就需要替代的有效抗疟药物。因此,本研究旨在确定提取物在小鼠模型中的抗疟潜力、安全性和耐药性发展情况。

方法

通过溶剂萃取获得甲醇提取物和乙酸乙酯提取物。对提取物进行急性毒性测定。此外,通过在500、250和125mg/kg/天的剂量下进行4天抑制试验,评估这两种提取物对ANKA株的抗疟活性。评估红细胞压积以确定贫血表现。最后,进行500mg/kg的连续药物压力实验和通过PCR进行DNA扩增。扩增产物进行桑格测序。

结果

在2000mg/kg时动物未出现毒性。重要的是,分别使用500mg/kg的甲醇提取物和乙酸乙酯提取物时,观察到高疟原虫血症抑制率分别为75.52%和75.30%。提取物能够逆转红细胞压积的降低。选择耐药表型为寄生虫清除延迟。然而,MDR1和CRT基因的核苷酸序列没有变化。

结论

这些结果为该植物未来作为抗疟药物的开发提供了空间。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/77f0/7875626/f205d012a6a9/JPATH2021-6165950.001.jpg

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