| Withering | 260–310{{Fb cs footer|s=[12]|date=October 2016}} 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 resistance to those climate conditions. Nevertheless, the preferred soil conditions for A. annua are light soils with deep topsoils and good drainage properties.[9] 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.[13] 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.[11] 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.[9] Nitrogen is required during early branching stages, an amount of approximately 70 kg N/ha is sufficient for the plant.[14] Phosphate on the other hand is required during the blooming stages. Phosphate fertilization can lead to a higher artemsinin content in the leaves.[15] The application of salicylic acid on the leaves shortly before harvesting the plant also can raise its artemisinin content.[16] 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.[9] 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.[17] Medicinal usesFolk medicineIn traditional Chinese medicine (TCM), A. annua is traditionally used to treat fever.[25] Due to duplication in ancient TCM scriptures, A. annua is more commonly referred to as qinghao ({{zh|c=青蒿|p=qīnghāo}}), the modern Chinese name for Artemisia carvifolia, as opposed to its current Chinese name huanghuahao.[18] Pharmacopoeia of the People's Republic of China defines qinghao in TCM as "dried aboveground parts of A. annua".[19] MechanismThe 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.[20] 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).[21] In 2015 artemisinin was shown to bind to a large number targets suggesting that it acts in a promiscuous manner.[22] ExtractionsIn 1971, scientists demonstrated the plant extracts had antimalarial activity in primate models, and in 1972, the active ingredient, artemisinin (formerly referred to as arteannuin), was isolated and its chemical structure described. Artemisinin may be extracted using a low boiling point solvent, 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.[23] 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.[24] 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 (ORAC) level.[25] Artemisia annua possesses the capacity to produce high phenolic compounds, which result in high antioxidant activity. Five major groups (coumarins, flavones, flavonols, phenolic acids and miscellaneous) containing over 50 different phenolic compounds were identified analyzing A. annua.[26]Flavonoids are generally known for their redox properties involved in the delay or inhibition of the initiation or propagation in oxidizing chain reactions.[26]Even though the beneficial effect of these phenolic compounds in association of 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.[26] 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.[26] Further researches in the synergistic effect of artemisinin and flavonoids and their biological interaction between malaria and cancer are needed.[26] Malaria treatmentResearch 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.[27][28] While most TCM herbs are boiled at high temperature that can damage the active ingredient in Artemisia annua,[28] one traditional source says that this herb is to be steeped in cold water;[29] knowing 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.[28] Artemisinin is a sesquiterpene lactone with an endoperoxide bridge and has been produced semisynthetically as an antimalarial drug. The efficacy of tea made from A. annua in the treatment of malaria is dubious. Research has found that artemesinin is not soluble in water and the concentrations in these infusions are considered insufficient to treat malaria.[30][31][32] In 2004, the Ethiopian Ministry of Health changed Ethiopia's first line antimalaria drug from sulfadoxine/pyrimethamine (Fansidar), which has an average 36% treatment failure rate, to artemether/lumefantrine (Coartem), 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.[33] A 2012 review said that artemisinin-based remedies are the most effective drugs for the treatment of malaria.[34] 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.[35] Despite global efforts in combating malaria, it remains a large burden for the population, particularly in tropical and subtropical regions.[50] Although WHO recommends artemisinin-based remedies for treating uncomplicated malaria, artemisinin resistance can no longer be ignored.[50] The causes that affected the emergence of artemisinin resistance include, for example, the use of artemisinin-based remedies.[50] Encouraging herbal alternatives are in the pipeline, but the only indelible solution for the eradication of malaria would be for the creation of an effective vaccination.[36] Emergence of artemisinin resistance has been identified in Cambodia and the border of Thailand.[54] It will likely spread to other endemic areas across the world in the impending future.[37] As of 2013, it seems that the pathogenic agent of malaria is becoming resistant to artemisinin-based drugs.[38][39] References1. ^The Plant List Artemisia annua L.
2. ^{{Cite book|url=http://www.forest.go.kr/kna/special/download/English_Names_for_Korean_Native_Plants.pdf |title=English Names for Korean Native Plants |publisher=Korea National Arboretum |year=2015 |isbn=978-89-97450-98-5 |location=Pocheon |pages=359 |access-date=25 January 2016 |via=Korea Forest Service |deadurl=yes |archiveurl=https://web.archive.org/web/20170525105020/http://www.forest.go.kr/kna/special/download/English_Names_for_Korean_Native_Plants.pdf |archivedate=25 May 2017 }}
3. ^{{cite web|title=BSBI List 2007 |publisher=Botanical Society of Britain and Ireland |url=http://www.bsbi.org.uk/BSBIList2007.xls |format=xls |accessdate=2014-10-17 |deadurl=yes |archiveurl=https://www.webcitation.org/6VqJ46atN?url=http://www.bsbi.org.uk/BSBIList2007.xls |archivedate=2015-01-25 }}
4. ^Flora of China Vol. 19, 20 and 21 Page 523 Sweet Annie, sweet sagewort, armoise annuelle Artemisia annua Linnaeus, Sp. Pl. 2: 847. 1753.
5. ^Flora of China Vol. 20–21 Page 691 黄花蒿 huang hua hao Artemisia annua Linnaeus, Sp. Pl. 2: 847. 1753
6. ^Flora of Pakistan
7. ^Altervista Flora Italiana, Assenzio annuale Artemisia annua L.
8. ^1 {{cite web|last1 = Anonymus|title = Artemisia annua (sweet wormwood)|url = http://www.kew.org/science-conservation/plants-fungi/artemisia-annua-sweet-wormwood|publisher = Royal Botanic Gardens|accessdate = November 25, 2015}}
9. ^1 2 3 4 {{cite book|last1 = World Health Organisation|title = WHO monograph on good agricultural and collection practices (GACP) for Artemisia annua L|date = 2006}}
10. ^{{Cite web|title = Using 1,000 Kernel Weight for Calculating Seeding Rates and Harvest Losses|url = http://www1.agric.gov.ab.ca/$department/deptdocs.nsf/all/agdex81|website = www1.agric.gov.ab.ca|date = 1993-09-01|accessdate = 2015-11-15|first = Government of Alberta, Alberta Agriculture and|last = Forestry}}
11. ^1 2 {{cite journal|last1 = Simonnet|first1 = X.|last2 = Quennoz|first2 = M.|last3 = Carlen|first3 = C.|title = New Artemisia annua hybrids with high artemisinin content|journal = XXVII International Horticultural Congress-IHC2006: International Symposium on Asian Plants with Unique Horticultural 769|date = 2006|pages = 371–373}}
12. ^{{cite book|last1 = World Health Organisation|title = WHO monograph on good agricultural and collection practices (GACP) for Artemisia annua L|date = 2006}}
13. ^{{cite journal|last1 = Müller|first1 = Meike|last2 = Brandes|first2 = Dietmar|title = Growth and development of Artemisia annua L. on different soil types|journal = Verhandlungen-Gesellschaft Fur Okologie|date = 1997|volume = 27|pages = 453–460}}
14. ^{{cite journal|last1 = Simon|first1 = James E|title = Artemisia annua L.: A promising aromatic and medicinal|journal = Advances in New Crops|date = 1990|pages = 522–526|display-authors=etal}}
15. ^{{cite journal|last1 = Kapoor|first1 = Rupam|last2 = Chaudhary|first2 = Vidhi|last3 = Bhatnagar|first3 = AK|title = Effects of arbuscular mycorrhiza and phosphorus application on artemisinin concentration in Artemisia annua L|journal = Mycorrhiza|date = 2007|volume = 17|issue = 7|pages = 581–587|pmid = 17578608|doi=10.1007/s00572-007-0135-4}}
16. ^{{cite journal|last1 = Pu|first1 = Gao-Bin|last2 = et. al|title = Salicylic acid activates artemisinin biosynthesis in Artemisia annua L|journal = Plant Cell Reports|date = 2009|volume = 28|issue = 7|pages = 1127–1135|pmid = 19521701|doi=10.1007/s00299-009-0713-3}}
17. ^{{Cite news|url = |title = Medicinal and Aromatic plants|last = Carlen|first = Christophe|date = 2015|work = Powerpoint Presentation in Lecture "Alternative Crops" at ETH Zürich.|access-date = |via = }}
18. ^{{cite web|last1=Liu|first1=Artemisia|title=【2015诺贝尔奖】青蒿素、青蒿、黄花蒿，究竟什么关系？|trans-title=2015 Nobel: Artemisinin, qinghao, and huanghuahao, how are they related?|url=http://www.guokr.com/article/440801/|publisher=guokr|accessdate=19 January 2017|language=zh|date=2015-10-09}}
19. ^{{cite book|title=中国药典2015版第一部|publisher=中国医药科技出版社|isbn=9787506773379|page=198|language=zh|quote=本品为菊科植物黄花蒿 Artemisia annua L. 的干燥地上部分。秋季花盛开时采割，除去老茎，阴干。}}
20. ^{{cite book |author1=Cumming JN |author2=Ploypradith P |author3=Posner GH |authorlink3=Gary H. Posner |title=Antimalarial activity of artemisinin (qinghaosu) and related trioxanes: mechanism(s) of action |journal=Adv. Pharmacol. |volume=37 |issue= |pages=253–97 |year=1997 |pmid=8891104 |doi=10.1016/S1054-3589(08)60952-7 |series=Advances in Pharmacology |isbn=9780120329380 }}
21. ^{{cite journal |author=Gary H. Posner & Paul M. O’Neil |title=Knowledge of the Proposed Chemical Mechanism of Action and Cytochrome P450 Metabolism of Antimalarial Trioxanes Like Artemisinin Allows Rational Design of New Antimalarial Peroxides |journal=Acc. Chem. Res. |year=2004 |volume=37 |pages=397–404 |doi=10.1021/ar020227u |pmid=15196049 |issue=6}}
22. ^{{cite journal | vauthors = Wang J, Zhang CJ, Chia WN, Loh CC, Li Z, Lee YM, He Y, Yuan LX, Lim TK, Liu M, Liew CX, Lee YQ, Zhang J, Lu N, Lim CT, Hua ZC, Liu B, Shen HM, Tan KS, Lin Q | title = Haem-activated promiscuous targeting of artemisinin in Plasmodium falciparum | journal = Nature Communications | volume = 6 | pages = 10111 | pmid = 26694030 | doi = 10.1038/ncomms10111 | pmc=4703832 | year=2015| bibcode = 2015NatCo...610111W }}
23. ^{{cite journal |vauthors=Duke SO, Paul RN |title=Development and Fine Structure of the Glandular Trichomes of Artemisia annua L. |journal=Int. J. Plant Sci. |volume=154 |issue=1 |pages=107–18 |year=1993 |doi=10.1086/297096 |jstor=2995610}}
{{cite journal |vauthors=Ferreira JF, Janick J |title=Floral Morphology of Artemisia annua with Special Reference to Trichomes |journal=Int. J. Plant Sci. |volume=156 |issue=6 |page=807 |year=1995 |doi=10.1086/297304 }}
24. ^{{cite web|url=https://www.theguardian.com/science/2015/oct/05/youyou-tu-how-maos-challenge-to-malaria-pioneer-led-to-nobel-prize|title=Tu Youyou: how Mao's challenge to malaria pioneer led to Nobel prize|author=Tom Phillips|date=October 6, 2015|publisher=The Guardian}}
25. ^{{Cite journal|title = Nutritional characterisation and antioxidant capacity of different tissues of Artemisia annua L.|url = http://www.sciencedirect.com/science/article/pii/S0308814609000776|journal = Food Chemistry|date = 2009-08-15|pages = 1240–1246|volume = 115|issue = 4|doi = 10.1016/j.foodchem.2009.01.033|first = Ebiamadon Andi|last = Brisibe|first2 = Umoren E.|last2 = Umoren|first3 = Fraideh|last3 = Brisibe|first4 = Pedro M.|last4 = Magalhäes|first5 = Jorge F. S.|last5 = Ferreira|first6 = Devanand|last6 = Luthria|first7 = Xianli|last7 = Wu|first8 = Ronald L.|last8 = Prior}}
26. ^1 2 3 4 {{Cite journal|title = Flavonoids from Artemisia annua L. as Antioxidants and Their Potential Synergism with Artemisinin against Malaria and Cancer|url = http://www.mdpi.com/1420-3049/15/5/3135|journal = Molecules|date = 2010-04-29|pages = 3135–3170|volume = 15|issue = 5|doi = 10.3390/molecules15053135|pmid = 20657468|pmc = 6263261|first = Jorge F. S.|last = Ferreira|first2 = Devanand L.|last2 = Luthria|first3 = Tomikazu|last3 = Sasaki|first4 = Arne|last4 = Heyerick}}
27. ^1 {{cite journal|doi=10.1038/448106a|title=Hard to swallow|year=2007|journal=Nature|volume=448|issue=7150|pages=105–6|pmid=17625521|bibcode=2007Natur.448S.105.}}
28. ^1 2 {{cite journal|doi=10.1016/j.cell.2011.08.024|title=Artemisinin: Discovery from the Chinese Herbal Garden|year=2011|last1=Miller|first1=Louis H.|last2=Su|first2=Xinzhuan|journal=Cell|volume=146|issue=6|pages=855–8|pmid=21907397|pmc=3414217}}
29. ^{{cite web|url=http://news.sciencemag.org/asia/2011/09/lasker-award-rekindles-debate-over-artemisinins-discovery |title=Lasker Award Rekindles Debate Over Artemisinin's Discovery | Science/AAAS | News |publisher=News.sciencemag.org |accessdate=2014-01-07|date=2011-09-29 }}
30. ^{{cite journal | title=Randomized controlled trial of a traditional preparation of Artemisia annua L. (Annual Wormwood) in the treatment of malaria | journal=Trans R Soc Trop Med Hyg | year=2004 | volume=98 | pages=318–21 | doi=10.1016/j.trstmh.2003.09.001 | pmid=15109558 | issue=5 | last1=Mueller | first1=Markus S | last2=Runyambo | first2=Nyabuhanga | last3=Wagner | first3=Irmela | last4=Borrmann | first4=Steffen | last5=Dietz | first5=Klaus | last6=Heide | first6=Lutz}}
31. ^{{cite journal | title=Pharmacokinetic study of artemisinin after oral intake of a traditional preparation of Artemisia annua L. (annual wormwood) | url=http://www.ajtmh.org/cgi/content/full/70/2/128 | date=1 February 2004| journal=Am J Trop Med Hyg | volume=70 | pages=128–32 | pmid=14993622 | issue=2 | last1=Räth | first1=K | last2=Taxis | first2=K | last3=Walz | first3=G | last4=Gleiter | first4=CH | last5=Li | first5=SM | last6=Heide | first6=L }}
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33. ^"Malaria Update", Focus on Ethiopia, April 2005, UN-OCHA website (accessed 12 March 2009)
34. ^{{cite journal| pmid=22855752| year=2012| last1=Fairhurst| first1=RM| last2=Nayyar| first2=GM| last3=Breman| first3=JG| last4=Hallett| first4=R| last5=Vennerstrom| first5=JL| last6=Duong| first6=S| last7=Ringwald| first7=P| last8=Wellems| first8=TE| last9=Plowe| first9=CV| last10=Dondorp| first10=AM| title=Artemisinin-resistant malaria: Research challenges, opportunities, and public health implications| volume=87| issue=2| pages=231–41| doi=10.4269/ajtmh.2012.12-0025| pmc=3414557| journal=The American Journal of Tropical Medicine and Hygiene}}
35. ^{{cite journal | pmid=22736625 | year=2013 | last1=Abolaji | first1=AO | last2=Eteng | first2=MU | last3=Ebong | first3=PE | last4=Brisibe | first4=EA | last5=Dar | first5=A | last6=Kabir | first6=N | last7=Choudhary | first7=MI | title=A safety assessment of the antimalarial herb Artemisia annua during pregnancy in Wistar rats | volume=27 | issue=5 | pages=647–54 | doi=10.1002/ptr.4760 | journal=Phytotherapy Research}}
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37. ^1 {{cite journal | pmid= 23656342 | year= 2013 | last1= Na-Bangchang | first1= K | last2= Karbwang | first2= J | title= Emerging artemisinin resistance in the border areas of Thailand | volume= 6 | issue= 3 | pages= 307–22 | doi= 10.1586/ecp.13.17 | journal= Expert Review of Clinical Pharmacology}}
38. ^News published on the Center for Strategic and International Studies website (Nov. 7, 2013)
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External links{{Commons category|Artemisia annua}}- Distribution of Artemisinin in Artemisia annua
- Project to improve artemesinin yield at the University of York (UK)
- Data sheet about Artemisia annua from Purdue University
{{Taxonbar|from=Q1308044}} 4 : Artemisia (genus)|Medicinal plants of Asia|Flora of Asia|Plants described in 1753 |