Artemisia annua
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.
The chemical compound artemisinin, which is isolated from A. annua, is a medication used to treat malaria due to Plasmodium falciparum, the deadliest species of malarial parasite. Discovery of artemisinin and its antimalarial properties made the Chinese scientist Tu Youyou recipient of the 2011 Lasker Prize and 2015 Nobel Prize in Physiology or Medicine.
Description
Artemisia annua belongs to the plant family of Asteraceae and is an annual short-day plant. Its stem is erect and brownish or violet-brown. The plant itself is hairless and naturally grows from 30 to 100 cm tall, although in cultivation plants can 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 A. annua developed in Switzerland can reach a leaf artemisinin content of up to 2%. Also, four new genotypes developed by a collaboration between the USDA and Purdue University with 2% leaf artemisinin were released for researchers involved in the production of artemisinin. The small flowers have a diameter of 2–2.5 mm and are arranged in loose panicles. Their color is greenish-yellow. 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 A. annua from seeding through to harvest is 190–240 days, depending on the climate and altitude of the production area. The plant is harvested at the beginning of flowering when the artemisinin content is highest. Dry leaf yields of A. annua plantations vary between 0.5 and 3 tonnes per hectare.| Growth Phases | Days after sowing |
| Seed germination | 4–10 |
| Appearance of 1st pair of leaves | 15–30 |
| Appearance of 2nd pair of leaves | 21–50 |
| Branching | 60–90 |
| Cessation of growth in height | 170–200 |
| Flowering | 190–240 |
| Full fruition | 230–280 |
| Withering | 260–310 |
In terms of the climate A. annua prefers sunny and warm conditions. Its optimal growth temperature lies between 20 and 25 °C. Annual temperature sums of 3500–5000 °C are required to guarantee a proper maturing. The rainfall during the growing season should not be less than 600 mm. Especially the seedlings of A. annua. are susceptible to drought or water logging. The mature plants on the other hand are quite resistant to those climate conditions. Nevertheless, the preferred soil conditions for A. annua are light soils with deep topsoils and good drainage properties. But it is reported, that the plant is adaptable to different soil types. Paired with the relatively low demand on the environment A. annua can have characteristics of a neophytic plant.
A. annua is best sown in rows to facilitate the removal of weeds, which has to be done mechanically or manually because herbicides are typically not used. It is recommended to sow 1.4 – 2 seeds per square meter. The fertilizer requirements are at a low level. Potassium should be used as base fertilizer. It is taken up by the plant during the whole growing season. Nitrogen is required during early branching stages, an amount of approximately 70 kg N/ha is sufficient for the plant. Phosphate on the other hand is required during the blooming stages. Phosphate fertilization can lead to a higher artemisinin content in the leaves. The application of salicylic acid to the leaves shortly before harvesting the plant also can raise its artemisinin content. Besides few viral diseases, A. annua has no major diseases that need to be controlled.
The harvest of the plant is best done when plants reach peak artemisinin, which may be in the state of flower budding, for early-flowering cultivars. However, for late flowering cultivars that were reported to reach peak artemisinin in early September in the United States, the harvest will happen about a month before the flowering stage when plants produce more artemisinin in leaves. This peak artemisinin in early September was observed for Brazilian, Chinese, and Swiss clones in West Virginia. Drying the plants before extraction will significantly increase artemisinin as dihydroartemisinic acid and artemisinic acid seem to be converted into artemisinin. The whole plant is harvested and cut into branches which are dried in the sun or an oven. Some report that drying artemisia plants at 45 °C for 24h increased artemisinin and maintained leaf antioxidant capacity. The dry branches are shaken or beaten to separate the leaves from the stem. The leaves are then packed into fabric bags and shipped for further processing. The optimum storage conditions are either 20 °C with 85% relative humidity or 30 °C with 30–40% RH.
Artemisinin and other phytochemicals
In 1971, scientists demonstrated that 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-point solvent, such as diethylether, is found in the glandular trichomes of the leaves, stems, and inflorescences, and is concentrated in the upper portions of plants 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. A. annua contains diverse phytochemicals, including polyphenols such as coumarins, flavones, flavonols, and phenolic acids which have unknown biological properties in vivo. Other phytochemicals include 38 sesquiterpenes. Dihydroartemisinin is the active metabolite of artemisinin, and artesunate is a water-soluble derivative of artemisinin. Recent research conducted in China and Korea has also demonstrated the presence of several nene, present in the essential oil.
Malaria treatment
Research to develop antimalarial drugs led to the discovery of artemisinin in the 1970s by the Chinese scientist Tu Youyou, who shared the 2015 Nobel Prize in Physiology or Medicine. An improved extract was obtained by using a low-temperature ether-based extraction method, further showing the artemisinin derivative artemether to be an effective antimalarial drug.Artemisinin is a sesquiterpene lactone with an endoperoxide bridge and has been produced 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 artemisinin is not soluble in water and the concentrations in these infusions are considered insufficient to treat malaria. A 2012 review stated that artemisinin-based remedies are the most effective drugs for the treatment of malaria. A 2013 review suggested that although A. annua may not cause hepatotoxicity, haematotoxicity, or hyperlipidemia, it should be used cautiously during pregnancy owing to a potential risk of embryotoxicity at a high dose.
The WHO has approved riamet, a combination of lumefantrine and artemether in repeat treatments over two days, producing efficacy of up to 98% against malaria.