Camille Roesch, Kutub Ashraf, Amélie Vantaux, Adriana A Marin, Steven P Maher, Jean-Francois Franetich, Nimol Kloeung, Sopheakvatey Ke, Hoa Thi My Vo, Dominique Mazier, Benoit Witkowski
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Artemisia extracts were tested in Ring Stage Survival Assays (RSA<sup>0-3 h</sup>) against Cambodian clinical isolates previously genetically and phenotypically characterized as artemisinin resistant or sensitive. Primary human hepatocytes and a human hepatoblastoma cell line (HepG2 cells) were used to assess the cytotoxicity of Artemisia extracts.</p><p><strong>Results: </strong>The study revealed a substantially decreased in vitro activity of A. annua extracts when tested on artemisinin-resistant parasites mutated in the Pfkelch13 gene (RSA<sub>50</sub> 0.137-2.56 g.L<sup>-1</sup>) compared to artemisinin-sensitive parasites (RSA<sub>50</sub> 0.080 g.L<sup>-1</sup>). Conversely, the A. afra extracts have a similar activity on the isolates tested whether they are sensitive or resistant to artemisinin (RSA<sub>50</sub> 0.537-0.758 g.L<sup>-1</sup>) However, the selectivity index for A. afra extracts was much lower than for A. annua extracts (A. afra: 4.628, 4.305 and 6.076 vs A. annua: 387.625, 226.350 and 12.099, respectively for WT, C580Y and R539T).</p><p><strong>Conclusions: </strong>Artemisia annua activity is driven by artemisinin, implicating the same resistance profiles and concerns associated with semisynthetic artemisinin derivatives. Artemisia afra showed artemisinin-independent antiplasmodial activity. 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引用次数: 0
摘要
背景：最近在非洲出现的青蒿素耐药性正在引起人们对使用基于黄花蒿和非洲蒿植物疗法的替代抗疟疾疗法的审查。本研究旨在确定黄花蒿和阿芙拉提取物对耐青蒿素恶性疟原虫分离株是否有活性，并确定抑制植物疗法的选择性。方法：采用青蒿提取物体外模拟寄生虫对人群饮用青蒿茶提取物的暴露。在环期生存试验（RSA0-3小时）中对柬埔寨临床分离株进行了青蒿提取物测试，这些分离株以前在遗传和表型上被表征为对青蒿素耐药或敏感。采用人原代肝细胞和人肝母细胞瘤细胞系HepG2细胞对青蒿提取物进行细胞毒性评价。结果：与青蒿素敏感疟原虫（RSA50 0.080 g.L-1）相比，青蒿素Pfkelch13基因突变的耐药疟原虫（RSA50 0.137 ~ 2.56 g.L-1）对青蒿素提取物的体外活性明显降低。相反，无论对青蒿素敏感还是耐药，afra提取物的活性相近（RSA50为0.537 ~ 0.758 g - l -1），但对afra提取物的选择性指数远低于黄花蒿提取物（黄花蒿提取物对WT、C580Y和R539T分别为4.628、4.305和6.076，黄花蒿提取物分别为387.625、226.350和12.099）。结论：黄花蒿的活性是由青蒿素驱动的，这意味着与半合成青蒿素衍生物具有相同的耐药特征和担忧。青蒿具有不依赖青蒿素的抗疟原虫活性。然而，这种活性的分子基础是未知的，可能没有足够的选择性，因此进一步的表征是非曲霉是必要的。
Assessment of the in vitro activity and selectivity of Artemisia afra and Artemisia annua aqueous extracts against artemisinin-resistant Plasmodium falciparum.
Background: The recent emergence of artemisinin resistance in Africa is drawing scrutiny toward the use of alternative anti-malarial therapy based on Artemisia annua and Artemisia afra phytotherapies. This study aimed to determine if either A. annua and A. afra extracts are active against artemisinin-resistant Plasmodium falciparum isolates and determine the selectivity of inhibitory phytotherapies.
Methods: Artemisia extracts were tested in vitro to mimic parasites exposure to extracts in population drinking Artemisia sp. teas. Artemisia extracts were tested in Ring Stage Survival Assays (RSA0-3 h) against Cambodian clinical isolates previously genetically and phenotypically characterized as artemisinin resistant or sensitive. Primary human hepatocytes and a human hepatoblastoma cell line (HepG2 cells) were used to assess the cytotoxicity of Artemisia extracts.
Results: The study revealed a substantially decreased in vitro activity of A. annua extracts when tested on artemisinin-resistant parasites mutated in the Pfkelch13 gene (RSA50 0.137-2.56 g.L-1) compared to artemisinin-sensitive parasites (RSA50 0.080 g.L-1). Conversely, the A. afra extracts have a similar activity on the isolates tested whether they are sensitive or resistant to artemisinin (RSA50 0.537-0.758 g.L-1) However, the selectivity index for A. afra extracts was much lower than for A. annua extracts (A. afra: 4.628, 4.305 and 6.076 vs A. annua: 387.625, 226.350 and 12.099, respectively for WT, C580Y and R539T).
Conclusions: Artemisia annua activity is driven by artemisinin, implicating the same resistance profiles and concerns associated with semisynthetic artemisinin derivatives. Artemisia afra showed artemisinin-independent antiplasmodial activity. However, the molecular basis of this activity is unknown and may not present a sufficient selectivity, thus further characterization of A. afra is essential.
期刊介绍：
Malaria Journal is aimed at the scientific community interested in malaria in its broadest sense. It is the only journal that publishes exclusively articles on malaria and, as such, it aims to bring together knowledge from the different specialities involved in this very broad discipline, from the bench to the bedside and to the field.
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