Artemisinin is a natural compound derived from the Artemisia annua plant, commonly known as sweet wormwood. This plant has a long history in traditional Chinese medicine, where it was recommended for treating fever symptoms as far back as 1596. The isolation of artemisinin in the 1970s marked a significant moment in modern medicine, transforming approaches to parasitic diseases.
Primary Application: Malaria Treatment
Artemisinin’s primary use is in treating malaria, especially against Plasmodium falciparum, the deadliest malaria parasite. Chinese scientist Tu Youyou first isolated the compound in 1972, later receiving the 2015 Nobel Prize for her discovery. This offered a new option when older antimalarial drugs, like chloroquine, were losing effectiveness due to widespread parasite resistance.
Artemisinin rapidly reduces malaria parasites in the blood. However, because it is quickly eliminated from the body, it is not used alone. Instead, it forms the basis of Artemisinin-based Combination Therapies (ACTs), combining it with a longer-acting partner drug to eliminate remaining parasites and prevent resistance.
The World Health Organization (WHO) recommends ACTs as the primary treatment for uncomplicated P. falciparum malaria. Artesunate, an artemisinin derivative, is effective for severe malaria and can be administered intravenously for rapid action. Despite ACTs’ success, artemisinin resistance has emerged in some regions, notably in the Greater Mekong subregion, prompting efforts to find new treatments and preserve current therapies’ effectiveness.
Investigational and Emerging Applications
Beyond malaria, artemisinin and its derivatives are being explored for their potential in other therapeutic areas. Research has shown promising activity against cancer cells, particularly those rich in iron. This effect is being studied across different cancer types.
They also show potential against other parasitic infections. Studies indicate efficacy against schistosomiasis (caused by blood flukes) and other protozoan parasites like Toxoplasma gondii (toxoplasmosis) and Leishmania major (leishmaniasis). These applications highlight the broad antiparasitic properties of artemisinin derivatives.
Artemisinin and its derivatives are also being researched for their immunomodulatory effects, showing promise in autoimmune and inflammatory conditions. Studies have explored their ability to regulate inflammation and immune responses in conditions like rheumatoid arthritis and inflammatory neurological diseases. These uses are largely experimental and not yet approved treatments.
How Artemisinin Works
Artemisinin’s unique chemical structure, specifically an endoperoxide bridge, is central to its mechanism of action. This bridge interacts with iron, abundant in malaria-infected red blood cells from hemoglobin digestion. The interaction with iron triggers the cleavage of the endoperoxide bridge, leading to reactive oxygen species, such as hydroxyl and carbon-centered free radicals.
These reactive molecules damage the parasite’s proteins, lipids, and nucleic acids, disrupting cellular functions and leading to its death. In cancer cells, a similar iron-dependent activation targets the high iron levels often found in these cells. This mechanism also disrupts calcium regulation within target cells, adding another layer to its effectiveness.
Safety and Administration Considerations
Artemisinin and its derivatives require careful consideration regarding safety and administration. Common side effects include gastrointestinal disturbances like nausea, dizziness, and tinnitus. While generally well-tolerated, rare cardiotoxicity, such as arrhythmias, has been observed.
For pregnant women, artemisinin derivatives, particularly in the first trimester, have been a subject of caution. Animal studies indicate potential embryotoxic and teratogenic effects, leading the WHO to historically recommend against their use for uncomplicated malaria during this period. However, for severe malaria in the first trimester, intravenous artesunate is recommended due to the high mortality risk of the disease.
Artemisinin is administered orally, rectally, or by injection, depending on the derivative and condition severity. Artemether, a lipid-soluble derivative, can cross the blood-brain barrier. It is important to use artemisinin only under medical supervision, especially with ACTs for malaria treatment, to ensure proper dosing, monitor for side effects, and manage resistance risk.