Artemisia annua

Artemisia annua, also known as sweet wormwood, sweet annie, sweet sagewort, annual mugwort or annual wormwood (Chinese: 黄花蒿; pinyin: huánghuāhāo), is a common type of wormwood native to temperate Asia, but naturalized in many countries including scattered parts of North America. Artemisia annua belongs 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 (TKW) averages around 0.03 g (in comparison, wheat has a TKW of approximately 45 g). 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 leave yields of Artemisia annua plantations vary between 0.5 and 3 t/ha. In terms of the climate A. annua prefers sunny and warm conditions. Its optimal growth temperature lies within 20 and 25 °C. Annual temperature sums of 3500–5000 °C (sum of temperatures higher 10 °C over one year) are required to guarantee a proper maturing. The rainfall during the growing season should not be less than 600 mm (annual rainfall higher 1150 mm). Especially the seedlings of A. annua. are susceptible to drought or water lodging. 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 Artemisia annua can have characteristics of a neophytic plant. Artemisia annua is best sown in rows. That facilitates weeding, which has to be done mechanically or manually since no chemical crop protection agents are admitted. It is recommended to sow 1.4 – 2 seeds per square meter. The fertilizer requirements are on 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 artemsinin content in the leaves. The application of salicylic acid on the leaves shortly before harvesting the plant also can raise its artemisinin content. Besides few viral diseases Artemisia a. has no major diseases that need to be controlled. The harvest of the plant is best done in the state of flower budding. The whole plant is harvested and cut into branches which are dried in the sun or in an oven. The drying temperature should not exceed 40 °C. The dry branches are shaken or beaten to separate the leaves from the stem. The leaves are then packed into fabric bags and shipped to further processing. It is important that the temperatures during transportation and storage never get higher than 40 °C, otherwise artemisinin gets volatile and is lost into the air. The leaves should not be crushed before long time storage (1 year). The optimal storage conditions are either 20 °C with 85% relative humidity (RH) or 30 °C with 30–40% RH. In traditional Chinese medicine (TCM), A. annua is traditionally used to treat fever. Due to duplication in ancient TCM scriptures, A. annua is more commonly referred to as qinghao (Chinese: 青蒿; pinyin: qīnghāo), 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'. The proposed mechanism of action of artemisinin involves cleavage of endoperoxide bridges by iron, producing free radicals (hypervalent iron-oxo species, epoxides, aldehydes, and dicarbonyl compounds) 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 the form of hemozoin). In 2015 artemisinin was shown to bind to a large number targets suggesting that it acts in a promiscuous manner.