| Artemisia annua | |
|---|---|
 | |
Scientific classification | |
| Kingdom: | Plantae |
| Clade: | Tracheophytes |
| Clade: | Angiosperms |
| Clade: | Eudicots |
| Clade: | Asterids |
| Order: | Asterales |
| Family: | Asteraceae |
| Genus: | Artemisia |
| Species: | A. annua |
| Binomial name | |
| Artemisia annua | |
| Synonyms[1] | |
Artemisia chamomillaC.Winkl. | |
Artemisia annua, also known assweet wormwood,[2]sweet annie,sweet sagewort,annual mugwort[3] orannual wormwood, is a common type ofwormwood native to temperate Asia, but naturalized in many countries including scattered parts of North America.[4][5][6][7]
Thechemical compoundartemisinin, which is isolated fromA. annua, is a medication used to treatmalaria due toPlasmodium falciparum, the deadliest species of malarial parasite.[8] Discovery of artemisinin and its antimalarial properties made the Chinese scientistTu Youyou recipient of the 2011Lasker Prize and 2015Nobel Prize in Physiology or Medicine.[9]
Artemisia annua belongs to the plant family ofAsteraceae 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 ofA. 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.[10] The artemisinin content in dried leaves is in between 0% and 1.5%.[11] New hybrids ofA. annua developed in Switzerland can reach a leaf artemisinin content of up to 2%.[12] 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.[13] 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 (TKW) averages around 0.03 g (in comparison, wheat has a TKW of approximately 45 g).[10][14]
The growing period ofA. 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.[11] Dry leaf yields ofA. annua plantations vary between 0.5 and 3tonnes perhectare.[12]
| Growth Phases[11] | 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 climateA. annua prefers sunny and warm conditions. Its optimal growth temperature lies between 20 and 25 °C. Annual temperature sums of 3500–5000 °C (sum of temperatures higher than 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 than 1150 mm). Especially the seedlings ofA. 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 forA. annua are light soils with deep topsoils and good drainage properties.[11] But it is reported, that the plant is adaptable to different soil types. Paired with the relatively low demand on the environmentA. annua can have characteristics of aneophytic plant.[15]
A. annua is best sown in rows to facilitate the removal of weeds, which has to be done mechanically or manually becauseherbicides are typically not used. It is recommended to sow 1.4 – 2 seeds per square meter.[12] 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.[11] Nitrogen is required during early branching stages, an amount of approximately 70 kg N/ha is sufficient for the plant.[16] Phosphate on the other hand is required during the blooming stages. Phosphate fertilization can lead to a higher artemisinin content in the leaves.[17] The application of salicylic acid to the leaves shortly before harvesting the plant also can raise its artemisinin content.[18] 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.[19] Drying the plants before extraction will significantly increase artemisinin as dihydroartemisinic acid and artemisinic acid seem to be converted into artemisinin.[20] 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.[21] 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.[11] The optimum storage conditions are either 20 °C with 85% relative humidity (RH) or 30 °C with 30–40% RH.[11]
In 1971, scientists demonstrated that the plant extracts hadantimalarial activity in primate models, and in 1972 the active ingredient, artemisinin (formerly referred to as arteannuin), was isolated and its chemical structure described.[8][22] Artemisinin may be extracted using a low-boiling-pointsolvent, such asdiethylether, is found in the glandulartrichomes of the leaves, stems, andinflorescences, and is concentrated in the upper portions of plants within new growth.[8][23]
The first isolation of artemisinin from the herb occurred from a military project known asProject 523, following the study of traditional medicine pharmacopoeias performed byTu Youyou and other researchers within the project.[24]A. annua contains diversephytochemicals, includingpolyphenols such ascoumarins,flavones,flavonols, andphenolic acids which have unknown biological propertiesin vivo.[25][26] Other phytochemicals include 38sesquiterpenes.[8]Dihydroartemisinin is the activemetabolite of artemisinin, and artesunate is awater-soluble derivative of artemisinin.[8] Recent research conducted in China and Korea has also demonstrated the presence of severalnene, present in the essential oil.[27][28][29]
Research to develop antimalarial drugs led to the discovery of artemisinin in the 1970s by the Chinese scientist Tu Youyou, who shared the 2015Nobel Prize in Physiology or Medicine.[9][22][30] An improved extract was obtained by using a low-temperatureether-based extraction method, further showing the artemisinin derivativeartemether to be an effective antimalarial drug.[8][22]
Artemisinin is asesquiterpenelactone with anendoperoxide bridge and has been produced as an antimalarial drug.[8] The efficacy of tea, made with either water orurine andA. annua, for the treatment of malaria is dubious, and is discouraged by theWorld Health Organization (WHO).[11][31] Research has found that artemisinin is not soluble in water and the concentrations in these infusions are considered insufficient to treat malaria.[32][33][34] A 2012 review stated that artemisinin-based remedies are the most effective drugs for the treatment ofmalaria.[35] A 2013 review suggested that althoughA. annua may not causehepatotoxicity,haematotoxicity, orhyperlipidemia, it should be used cautiously during pregnancy owing to a potential risk ofembryotoxicity at a high dose.[36]
The WHO has approvedriamet (Coartem), a combination oflumefantrine (120 mg) and artemether (an artemisinin derivative extracted with ether, 20 mg) in repeat treatments over two days, producing efficacy of up to 98% against malaria.[8]
The proposedmechanism of action of artemisinin involves cleavage of endoperoxide bridges by iron, producingfree radicals (hypervalent iron-oxo species,epoxides,aldehydes, anddicarbonyl compounds) which damage biological macromolecules causingoxidative stress in the cells of the malaria parasite.[8][37] Malaria is caused byapicomplexans, primarilyPlasmodium falciparum, which largely reside inred blood cells and contain iron-richheme-groups (in the form ofhemozoin).[8][38] In 2015, artemisinin was shown to bind to a large number of cell targets, indicating its potential for diverse effects.[39]
Despite global efforts in combating malaria, it remains a large burden for the population, particularly in tropical and subtropical regions.[8][40] As of 2013, it seems that the pathogenic agent of malaria is becoming resistant to artemisinin-based drugs.[41][42] Emergence of artemisinin resistance has been identified in Cambodia and the border of Thailand.[43] Although the WHO recommends artemisinin-based remedies for treating uncomplicated malaria, artemisinin resistance has become a concern.[40] The causes that affected the emergence of artemisinin resistance include the use of artemisinin-based remedies.[40] Encouraging herbal alternatives are in the pipeline, but a more dependable solution for the eradication of malaria would be the creation of an effectivevaccination.[40] Resistance will likely spread to other endemic areas across the world.[43]
Intraditional Chinese medicine (TCM),A. annua is prepared with water to treatfever.[8][30] Owing to duplication in ancient TCM sources,A. annua is more commonly referred to asqinghao (Chinese:青蒿;pinyin:qīnghāo), the modern Chinese name forArtemisia carvifolia, as opposed to its current Chinese namehuanghuahao.[44]
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