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Discovery and repurposing of artemisinin

《医学前沿（英文）》 2022年第16卷第1期页码 1-9 doi: 10.1007/s11684-021-0898-6

摘要： Malaria is an ancient infectious disease that threatens millions of lives globally even today. The discovery of artemisinin, inspired by traditional Chinese medicine (TCM), has brought in a paradigm shift and been recognized as the “best hope for the treatment of malaria” by World Health Organization. With its high potency and low toxicity, the wide use of artemisinin effectively treats the otherwise drug-resistant parasites and helps many countries, including China, to eventually eradicate malaria. Here, we will first review the initial discovery of artemisinin, an extraordinary journey that was in stark contrast with many drugs in western medicine. We will then discuss how artemisinin and its derivatives could be repurposed to treat cancer, inflammation, immunoregulation-related diseases, and COVID-19. Finally, we will discuss the implications of the “artemisinin story” and how that can better guide the development of TCM today. We believe that artemisinin is just a starting point and TCM will play an even bigger role in healthcare in the 21st century.

关键词： artemisinin drug repurposing cancer inflammation COVID-19 traditional Chinese medicine

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Purification of artemisinin from quercetin by anti-solvent crystallization

Chandrakant R. MALWADE, Haiyan QU, Ben-Guang RONG, Lars P. CHRISTENSEN

《化学科学与工程前沿（英文）》 2013年第7卷第1期页码 72-78 doi: 10.1007/s11705-013-1305-x

摘要： In the present work, anti-solvent crystallization of artemisinin from four different organic solvents (methanol, ethanol, acetonitrile, and acetone) was studied. Water was used as anti-solvent. The effect of an impurity (quercetin) on the performance of anti-solvent crystallization of artemisinin was investigated. The fundamental process data such as solubility of artemisinin in pure organic solvents and their binary mixtures with varying composition water were measured at room temperature. The solubility of quercetin was measured only in pure organic solvents at room temperature. Anti-solvent crystallization experiments were designed based on the fundamental process data determined. Firstly, the anti-solvent crystallization of artemisinin without impurity was performed from all four organic solvents and then the experiments were repeated with addition of an impurity (quercetin) while keeping all other process parameters constant. Two different concentrations of impurity, i.e., 10% and 50% of its solubility, in the respective organic solvents at room temperature were used. The effect of impurity on performance of anti-solvent crystallization was evaluated by comparing the yield and purity of the artemisinin obtained with those in the absence of impurity. Results of the present work demonstrated that the presence of quercetin in the solution does not affect the final yield of artemisinin from the solution of each of four organic solvents used. However, the purity of artemisinin crystals were reduced when quercetin concentration was 50% of its solubility in all solvents studied.

关键词： anti-solvent crystallization artemisinin quercetin solubility Artemisia annua

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青蒿素——一种从中药中发现的神奇药物 Review

王继刚, 徐承超, 王彦钧, 李玉洁, 廖福龙, 姜廷良, 屠呦呦

《工程（英文）》 2019年第5卷第1期页码 32-39 doi: 10.1016/j.eng.2018.11.011

摘要：

青蒿素及其衍生物是治疗疟疾最重要且最具影响力的一类药物。自20世纪70年代初发现青蒿素以来，国际上在研究这种非凡的植物化学药物及探明其独特的化学和药理特性方面取得了巨大进展。现今，虽然青蒿素及其衍生物仍然是抗疟的支柱药物，它们的持续应用和发展也面临许多挑战。这些挑战包括青蒿素治疗疟疾过程中出现的耐药现象以及青蒿素在其它疾病中的应用。在这篇综述中，我们描述了青蒿素类药物的早期发现和发展过程、应用现状以及未来的发展前景。另外，我们总结了当前的青蒿素机制研究情况并提出了我们自己的看法，同时强调了机制研究对于青蒿素类药物在抗疟以及其它疾病治疗中的重要性。

关键词：青蒿作用机制疟疾抗癌

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通过鉴定关键靶标蛋白探究青蒿素抗疟机制 Article

高鹏, 王建友, 陈嘉鋆, 谷丽维, 王晨, 徐丽婷, Yin Kwan Wong, 张会敏, 徐承超, 戴凌云, 王继刚

《工程（英文）》 2023年第31卷第12期页码 86-97 doi: 10.1016/j.eng.2023.06.001

摘要：

青蒿素（ART）及其衍生物的广泛使用极大地减轻了全球疟疾负担。然而，疟疾仍然对全球健康构成严重威胁。尽管ART抗疟机制的研究在近年已经取得了重大进展，但其最关键治疗靶点蛋白和途径仍然是未知的。当前，在东南亚等地区已经出现了ART耐药性的迹象，因此迫切需要了解ART确切的抗疟机制。在本研究中，我们使用质谱-细胞热转移技术（MS-CETSA）和转录组学分析联用策略来鉴定ART的潜在靶标蛋白。然后对五个潜在靶蛋白进行了一系列验证实验，证明了ART可能通过干扰疟原虫的氧化还原稳态，脂质代谢和蛋白质合成过程来发挥抗疟作用。总之，本研究为ART的抗疟机制研究提供了新的视角，并确定了几种参与寄生虫生存的关键蛋白，这些蛋白可以作为防治疟疾的靶标。

关键词：青蒿素抗疟靶标鉴定 MS-CETSA 转录组学