The secondary plant pigment artemisinin from the flowers and leaves of the annual mugwort is used to treat malaria. The drug is used primarily in areas where other antimalarial drugs are ineffective against multidrug-resistant pathogens. The remedy is already mentioned in traditional Chinese medicine, which is thousands of years old.
What is artemisinin?
The secondary plant pigment artemisinin from the flowers and leaves of annual mugwort is used to treat malaria. Artemisinin belongs to the substance class of sesquiterpenes. These chemical compounds, which are quite common in the plant kingdom, are composed of three isoprene units. The drug extracted from the annual mugwort (Artemisia annua) contains, in addition to a trioxane ring system, a pharmacologically crucial peroxide bridge. In 1971, the Chinese Tu Youyou isolated and described the active ingredient for the first time, and in subsequent years proved its positive effects in the fight against malaria tropica. This is because artemisinin is a drug that acts very quickly and reliably. The remedy can be extracted from the dried leaves and flowers of plants grown in China, Vietnam and East Africa. Since this process is quite expensive and time-consuming, artemisinin is now also obtained biotechnologically with the help of genetically modified yeasts. Because artemisinin itself is quite unstable, its semisynthetic derivatives artesunate, artemotil, artemether, and others are usually used in medicines.
Pharmacological action
Although the exact mechanism of action of artemisinin is not known yet (2015). But scientists assume that the rather unusual peroxide structure is crucial. This is because it breaks down into free radicals when it encounters a large number of iron ions. Not only human red blood cells (erythrocytes) contain a lot of iron, but also the malaria-causing plasmodia. These parasites are transmitted to humans by the Anopheles mosquito and colonize the red blood cells. When the single-cell pathogens attack an erythrocyte, they feed on the blood pigment hemoglobin. As they accumulate the iron contained in this, the free radicals of the drug can kill the plasmodia. Studies indicate that artemisinin also inhibits a specific calcium transporter in the cell membrane of the protozoa. It is also possible that artemisinin can kill cancer cells in a similar way. This is because cancer cells also contain high concentrations of iron. Initial experiments with cell cultures confirm this theory. Likewise, the drug appears to be effective against the tropical infectious disease schistosomiasis.
Medical application and use
The World Health Organization (WHO) recommends the use of artemisinin or its derivatives primarily in countries where other drugs are ineffective because of known multidrug-resistant strains of Plasmodium falciparum. While artemisinin was considered very effective for a long time, pathogens are now known from several countries that are also resistant to the active ingredient due to mutations. To prevent increasing resistance to artemisinin, a combination therapy with other antimalarial drugs should therefore always be used. This treatment is often abbreviated as ACT (artemisinin-based combination therapy). Because of the short half-life, the tablets must be taken at fixed intervals over several days. Dosage in children is based on body weight. In the severe form of malaria tropica, the derivative artesunate can be injected directly into the vein or muscle. In both children and adults, this drug is considered the drug of choice in emergencies. Whether a tea made from Artemisia annua is also sufficiently effective against plasmodia is disputed among scientists.
Risks and side effects
Artemisinin and its semisynthetic derivatives are well tolerated by children and adults at doses that control malaria. If side effects occur, in many cases they resemble typical malaria symptoms. These include nausea, vomiting, loss of appetite and dizziness. Likewise, the heart rate may increase. Joint and muscle pain, fatigue and sleep problems are also possible. Mild blood abnormalities also sometimes occur as a result of ingestion. Rarely, dangerous allergic reactions to the drug occur.This may be manifested by rash, swelling, difficulty breathing or swallowing. Iron preparations taken at the same time as artemisinin may lead to interactions. Combination therapy with other drugs may increase various side effects. Nevertheless, WHO strongly advises against monotherapies with artemisinin alone. Resistance may otherwise render the drug ineffective.
