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Tommy Li
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Artemisinin

Written by Tommy Li and Jerry Lau


Artemisinin is one of the most widely used therapies against malaria worldwide.It is also called Qinghao, which was extracted from Artemisia annua (sweet wormwood). First isolated through Eastern medicine and tested in the 1970s in China, Artemisinin and its derivatives have a complex mode of action and can cause widespread injury to many parts of the parasite (1). In the ancient time, herbs containing artemisinin were used to treat outspread malaria. Recently, in the rise of an unprecedented pandemic, even more promising uses of Artemisinin have been found and are being studied. It has been shown to possess selective anticancer properties with demonstrated cytotoxic effects in vitro and in vivo. But why does Artemisinin show these aforementioned properties? It appears they are in part due to mediated artemisinin-induced changes in multiple signaling pathways, interfering simultaneously with multiple known indicators of cancer (2). However more information is needed to provide a definitive answer on placing the medication as a recognized therapy in the oncology field.


Besides treating cancers, Artemisinin and the class of drugs it belongs to, antimalarials. Artemisinin is sesquiterpene lactone endoperoxide with an active moiety, dihydroartemisinin. The endoperoxide bridge is activated by heme iron binding, resulting in oxidative stress, inhibition of protein and nucleic acid synthesis, ultrastructural changes, and a decrease in parasite growth and survival. Once an infected female anopheles mosquito bites a person, malarial parasites enter the body. They then entered the hepatocytes via circulation and began its asexual reproduction called exoerythrocytic stage. The hepatocytes then rupture, releasing more merozoites in the blood and the asexual erythrocytic stage begins to show symptoms. Erythrocytic schizonts replicate and release, and infect other erythrocytes. Artemisinin treats the erythrocytic schizonts. However, no drugs act on sporozoites. So complete prophylaxis is not possible. No one agent can target all the stages and hence combination therapy is needed (4). Note that WHO does not recommend artemisinin use in first trimester pregnant women.


During the recent 2019 - 2021 COVID - 19 pandemic, Artemisinin has also been recognized as a promising treatment to tackle the COVID-19. For example, in a 2021 Trends in Parasitology Journal, it was shown that Artemisinin based combination therapies (known as ACTs for short) inhibited severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The study shows anti inflammatory effects especially pronounced in interleukin-6 (IL-6). This interleukin plays a key role in the development of severe coronavirus disease 2019 (COVID-19). This sort of evidence is sufficient enough to support more approval of clinical studies that investigate this relationship between use of ACTs and antiviral activity shown in COVID-19 patients (3).


Artemisinin, a drug that has a secret two thousands of years of history, hides in the Chinese herbalists. It has shown the world its power to solve malaria problems globally when combined with other malaria medicines. Today, there are still many secret formulas hiding in the ancient book and waiting for us to discover their effects and exact mechanisms. Only dedications with good luck can uncover their mysterious mechanism of actions. The world is waiting for them to shine again.



References

  1. Talman AM, Clain J, Duval R, Ménard R, Ariey F. Artemisinin Bioactivity and Resistance in Malaria Parasites. Trends Parasitol. 2019;35(12):953-963.

  2. Wong YK, Xu C, Kalesh KA, et al. Artemisinin as an anticancer drug: Recent advances in target profiling and mechanisms of action. Med Res Rev. 2017;37(6):1492-1517.

  3. Krishna S, Augustin Y, Wang J, et al. Repurposing Antimalarials to Tackle the COVID-19 Pandemic [published correction appears in Trends Parasitol. 2021 Apr;37(4):357]. Trends Parasitol. 2021;37(1):8-11.

  4. Daher, A., Aljayyoussi, G., Pereira, D. et al. Pharmacokinetics/pharmacodynamics of chloroquine and artemisinin-based combination therapy with primaquine. Malar J 18, 325 (2019). https://doi.org/10.1186/s12936-019-2950-4

  5. Daher, A., Pereira, D., Lacerda, M.V.G. et al. Efficacy and safety of artemisinin-based combination therapy and chloroquine with concomitant primaquine to treat Plasmodium vivax malaria in Brazil: an open label randomized clinical trial. Malar J 17, 45 (2018). https://doi.org/10.1186/s12936-018-2192-x




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