by James Odell, OMD, ND, L.Ac.
Artemisia annua has been used in China for more than 2000 years to treat fevers and more recently used in the treatment of the chloroquine-resistant and cerebral malaria (Plasmodium falciparum). Much focus has now been paid to its effectiveness in the treatment of SARS-CoV-2 (Covid-19). Its ancient Chinese name Qing Hao literally means “green herb.” Qing Hao was mentioned in the ancient text (168BC) Wu Shi Er Bing Fang or “Recipes for Fifty-Two Ailments”, as a remedy for fevers. The genus Artemisia consists of over 400 species, many of which have an aromatic, bitter taste. Herbal extracts of Artemisia annua have been used for thousands of years in other parts of the world, particularly Southeast Asia, Africa, India, and South America, to treat malaria and a variety of infectious diseases. Apart from its anti-malarial properties, Artemisia annua has been used in traditional Chinese medicine to stimulate hair growth, to promote longevity, as a food additive, as an anti-inflammatory, as well as a treatment for numerous external illnesses including hemorrhoids, lice and boils.
Artemisia is a large, diverse plant genus with between 200 and 400 species and consists of hardy herbs and shrubs belonging to the Magnoliopsida class of flowering plants. Artemisia annua is an annual shrub of 50–150 cm in height. The shrub grows in temperate climates and is most widespread in China and Vietnam, but is also cultivated in East Africa, the United States, Russia, India, Brazil, and several other countries.1, 2 The reproduction of the shrub occurs by insects, self-pollination, and wind distribution.3
Artemisia annua Chemical Properties
The essential oil of Artemisia annua is rich in mono- and sesquiterpenes with numerous medicinal properties. Significant variations in its percentage and composition have been identified (main constituents may be camphor (up to 48%), germacrene D (up to 18.9%), artemisia ketone (up to 68%), and 1,8 cineole (up to 51.5%)). The oil has been subjected to numerous studies supporting exciting antiparasitic, antibacterial, antiviral, and antifungal activities. One of the more medicinal components found in Artemisia annua is artemisinin, first isolated in China in 1971.4
Artemisinin is the constituent with the greatest antimalarial activity. Up to 42% of the total artemisinin content is found in the upper leaves, where it accumulates in the glandular trichomes of the leaves. Artemisinin has been found in only two other species, Artemisia apiacea and Artemisia lance 5, and since that time its efficacy against malaria has been amply demonstrated.6, 7, 8, 9, 10, 11
The total amount of artemisinin found in different varieties of Artemisia annua varies slightly depending on extraction methods, different collection periods, different sample preparation, and different environmental influences.12 The artemisinin content in the plant exhibits the highest quantities usually just before flowering. Except for Artemisia annua, artemisinin is also present in Artemisia apiacea and Artemisia lancea, but only in minor quantities.13
Nowadays, many researchers are still investigating the effect of artemisinin and its analogues on the malarial parasite (Plasmodium) by modifying the structure of peroxides, ethers and ozonides in artemisinin. This improves the killing rate of plasmodium parasites for both in vitro and in vivo models as well as a faster clinical response for humans.14
Antimalarial Mechanism of Action of Artemisia annua
Malaria is one of the most severe public health problems worldwide. It is a leading cause of death and disease in many developing countries, where young children and pregnant women are the groups most affected. Worldwide an estimated 450,000 deaths annually (around 1200 per day) are attributed to malaria. This infection is caused primarily by the Plasmodium falciparum parasite, which largely reside in red blood cells and contains iron-rich heme-groups (in the form of hemozoin). Such hematophagous organisms digest hemoglobin and release high quantities of free heme, which is the non-protein component of hemoglobin. As a result, hemozoin pigment and other toxic factors such as glycosylphosphatidylinositol (GPI) are also released into the blood. These products, particularly the GPI, activate macrophages and endothelial cells to secrete cytokines and inflammatory mediators such as tumor necrosis factor, interferon-γ, interleukin-1, IL-6, IL-8, macrophage colony-stimulating factor, and lymphotoxin, as well as superoxide and nitric oxide. These inflammatory cytokines and mediators can cause significant damage to organs and tissues.15, 16, 17
The parasite is fairly shielded from attack by the body's immune system since it resides within the liver and blood cells for much of its human life cycle and is relatively invisible to immune surveillance. However, circulating infected blood cells are destroyed in the spleen. To avoid this fate, the Plasmodium falciparum parasite displays adhesive proteins on the surface of the infected blood cells, causing the blood cells to stick to the walls of small blood vessels, thus sequestering the parasite from passage through the general circulation and the spleen. Sequestered red blood cells can breach the blood-brain barrier and cause cerebral malaria. Artemisinin is also active against other parasite species such as Toxoplasma and Babesia that do not contain hematin.