Artemisia annua, also known as sweet wormwood, sweet annie, sweet sagewort, annual mugwort or annual wormwood, is a common type of wormwood native to temperate Asia, but naturalized in many countries including scattered parts of North America.
Characteristics
Artemisia annuabelongs to the plant family of Asteraceae and is an annual short-day plant. Its stem is erect brownish or violet brown. The plant itself is hairless and naturally grows from 30 to 100 cm tall, although in cultivation it is possible for plants to reach a height of 200 cm. The leaves of A. annua have a length of 3–5 cm and are divided by deep cuts into two or three small leaflets. The intensive aromatic scent of the leaves is characteristic. The artemisinin content in dried leaves is in between 0% and 1.5%. New hybrids of Artemisia annua developed in Switzerland can reach a leaf artemisinin content of up to 2%. The small flowers have a diameter of 2–2.5 mm and are arranged in loose panicles. Their color is green-yellowish. The seeds are brown achenes with a diameter of only 0.6–0.8 mm. Their thousand-kernel weight averages around 0.03 g.
Agricultural practice
The growing period of Artemisia annua from seeding till harvest is 190–240 days, depending on the climate and altitude of the production area. The plant should be harvested at the beginning of flowering. At that time the artemisinin content is the highest. Dry leaf yields of Artemisia annua plantations vary between 0.5 and 3 t/ha.
Medicinal uses
Folk medicine
In traditional Chinese medicine, A. annua is traditionally used to treat fever. Due to duplication in ancient TCM scriptures, A. annua is more commonly referred to as qinghao, the modern Chinese name for Artemisia carvifolia, as opposed to its current Chinese name huanghuahao. Pharmacopoeia of the People's Republic of China defines qinghao in TCM as "dried aboveground parts of A. annua".
Mechanism
The proposed mechanism of action of artemisinin involves cleavage of endoperoxide bridges by iron, producing free radicals which damage biological macromolecules causing oxidative stress in the cells of the parasite. Malaria is caused by apicomplexans, primarily Plasmodium falciparum, which largely reside in red blood cells and itself contains iron-rich heme-groups. In 2015 artemisinin was shown to bind to a large number targets suggesting that it acts in a promiscuous manner.
Extractions
In 1971, scientists demonstrated the plant extracts had antimalarial activity in primate models, and in 1972, the active ingredient, artemisinin, was isolated and its chemical structure described. Artemisinin may be extracted using a low boiling pointsolvent, such as diethylether, and is found in the glandular trichomes of the leaves, stems, and inflorescences, and it is concentrated in the upper portions of plant within new growth. The first isolation of artemisinin from the herb occurred from a military project known as Project 523, following the study of traditional medicine pharmacopoeias performed by Tu Youyou and other researchers within the project.
Antioxidant activity
Apart from the active compound Artemisinin, recent studies show that A. annua is one of the four medical plants with the highest Oxygen radical absorbance capacity level. Artemisia annua possesses the capacity to produce high phenolic compounds, which result in high antioxidant activity. Five major groups containing over 50 different phenolic compounds were identified analyzing A. annua. Flavonoids are generally known for their redox properties involved in the delay or inhibition of the initiation or propagation in oxidizing chain reactions. Even though the beneficial effect of these phenolic compounds on a great number of diseases is often discussed, different studies show beneficial effects of flavonoids compound produced by A. annua. It has been stated that there is a negative correlation between the presence of the mentioned components and cardiovascular diseases, cancer and parasitic disease such as malaria.
Artemisinin and flavonoids
In the last 20 years researchers focused on the activity of artemisinin against malaria. Therefore, fewer studies have been done about the relationship between flavonoids and cancer. Despite that, recent studies show that the flavonoids present in the A. annua leaf are linked to suppression of CYP450 enzymes responsible for altering the absorption and metabolism of artemisinin in the body. Further researches in the synergistic effect of artemisinin and flavonoids and their biological interaction between malaria and cancer are needed.
Malaria treatment
Research to develop antimalarial drugs led to the discovery of artemisinin, a compound which is extracted from Artemisia annua, in the 1970s by Chinese scientist Tu Youyou, for which she shared the 2015 Nobel Prize in Physiology or Medicine. While most TCM herbs are boiled at high temperature that can damage the active ingredient in Artemisia annua, one traditional source calls for this herb to be steeped in cold water. Noting this, scientists found that a better extract was obtained by using a low-temperature ether-based extraction method. Purification processes were used to isolate the active molecule, and clinical trials showed the active ingredient to be an effective drug. Artemisinin is a sesquiterpenelactone with an endoperoxide bridge and has been produced semisynthetically as an antimalarial drug. The efficacy of tea, made with either water or urine and A. annua, for the treatment of malaria is dubious, and is discouraged by the World Health Organization. Research has found that artemesinin is not soluble in water and the concentrations in these infusions are considered insufficient to treat malaria. In 2004, the Ethiopian Ministry of Health changed Ethiopia's first line antimalaria drug from sulfadoxine/pyrimethamine, which has an average 36% treatment failure rate, to artemether/lumefantrine, a drug therapy containing artemesinin which is 100% effective when used correctly, despite a worldwide shortage at the time of the needed derivative from A. annua. A 2012 review said that artemisinin-based remedies are the most effective drugs for the treatment of malaria. A 2013 review suggested that although Artemisia annua may not cause hepatotoxicity, haematotoxicity, or hyperlipidemia, it should be used cautiously during pregnancy due to a potential risk of embryotoxicity at a high dose.
Artemisinin resistance
Despite global efforts in combating malaria, it remains a large burden for the population, particularly in tropical and subtropical regions. As of 2013, it seems that the pathogenic agent of malaria is becoming resistant to artemisinin-based drugs. Emergence of artemisinin resistance has been identified in Cambodia and the border of Thailand. Although WHO recommends artemisinin-based remedies for treating uncomplicated malaria, artemisinin resistance has become a concern. The causes that affected the emergence of artemisinin resistance include the use of artemisinin-based remedies. Encouraging herbal alternatives are in the pipeline, but a more dependable solution for the eradication of malaria would be the creation of an effective vaccination. Resistance will likely spread to other endemic areas across the world.
In April 2020, President Andry Rajoelina of Madagascar, speaking at the launch of a drink made from a variety of herbs though predominantly from A. annua and ravensara, recommended the product as a treatment for COVID-19 patients and said students' return to schools would be conditioned on their consumption of it. However, despite anecdotal reports of the use of A. annua against COVID-19 in China, there is no clear evidence of the effectiveness of the tea against the infection, and no clinical studies have been conducted. The WHO warns that the drink's efficacy as a treatment for COVID-19 is unproven, while the African Union is seeking technical data from Madagascar and has asserted that there will be a scientific review based on "global technical and ethical norms."
