Written by Klara Rombauts, Arne Heyerick and the CAM-Cancer Consortium.
Updated January 29, 2015

Artemisia annua

What is it?

Artemisia annua, also known as sweet wormwood, sweet annie, sweet sagewort and annual wormwood (Chinese: qīnghāo), is a common type of wormwood that is native to temperate Asia but naturalized throughout the world.1 It belongs to the family of Asteraceae and has fern-like leaves, bright yellow flowers and a camphor-like scent. Glandular structures (trichomes) producing a wide range of bioactive compounds (mostly terpenoids) can be found on the surface of leaves, stems and flowers.

Ingredient(s)

The phytochemical composition of A. annua has been reviewed in great detail by Bhakuni et al.2 The most relevant compounds are sesquiterpenoids (ex. artemisinin), triterpenoids, flavonoids (polymethoxylated flavonoids), chromenes1 and essential oil components. The content of an A. annua extract depends on the solvent used for extraction. Aqeous extracts seem to contain less polymethoxylated flavonoids than alcohol extracts, but they do contain a high amount of mono-caffeoyl- and mono-feruloyl-quinic acids, di-caffeoyl- and di-feruloyl-quinic acids. Alcoholic extracts seem to contain the highest antioxidant potential. Also the flavonoids casticin and artemetin that have shown synergism with artemisinin against malaria are less extracted in aqeous extracts.3-5

Besides A. annua itself, this summary also reviews current literature on artesunate, dihydroartemisinin and artemether, which are semi-synthetic derivatives of artemisinin. Far more research has been published on the effect of these compounds than on artemisinin itself. Arteether, another semisynthetic derivative that has been used in antimalarial treatment has not been the focus of anticancer research to date.

Application and dosage

There is no documented safe or effective dose for the possible use of A. annua derived products for the treatment of cancer in adults or children. The Chinese pharmacopoeia lists the dry herb as a remedy for fever and malaria. The daily dose described is 4.5 to 9 grams of dried herb to be prepared as a tea infusion with boiling water. The artemisinin content varies from 0.02% to 1.1% of the dry weight.6 In addition, artemisinin and its semisynthetic derivatives are used in antimalarial treatment in artemisinin-based combination therapies, with daily doses between 100 and 200mg.7

History

Artemisia annua was used by Chinese herbalists in ancient times to treat specific fevers, but had fallen out of common use until it was rediscovered in 1970 when the Chinese Handbook of Prescriptions for Emergency Treatments (340 AD) was recovered. This ancient pharmacopeia contained a recipe for a tea from the dried leaves of A. annua to be used in case of specific fevers. In 2010 it was discovered that A. annua has already been cited in the earliest Chinese medical prescriptions, the Mawagndui tomb texts dating back to 168 B.C. There, it is prescribed for female haemorrhoids and as a sexual tonic, being mixed with other herbs, including cinnamon and ginger, and administered in boiled urine.8 In 1971, scientists demonstrated that the plant extracts had antimalarial properties in primate models.9

Mechanism of anti-cancer action

Artemisinin, the natural endoperoxide of A. annua, and its semisynthetic derivates dihydroartemisinin, arthemether, artheether and artesunate are considered to be the primary active constituents for antimalarial and anti-cancer activity.10,11 Also the polymethoxyflavonoids are indicated as important compounds with potential anticancer activity. Cancer cell lines show a differential sensitivity as well as resistance to this group of compounds. Different genes which influence the sensitivity or the resistance to treatment have been identified. These genes could potentially function as markers indicating the expected efficacy of a clinical therapy.12,13 In contrast to popular belief that the cytotoxic activities would only be due to the non-specific generation of reactive oxygen species, it has become clear that artemisinin-related endoperoxides additionally have various specific molecular targets and can significantly influence the expression of key regulatory proteins of the cell cycle.10,11,13,14 Artemisinin-related endoperoxides were found to significantly inhibit angiogenesis and also to induce apoptosis.10,15 Iron plays a crucial role in the cytotoxic activities of artemisinin-related endoperoxides through the generation of both ROS and carbon-centred radicals. In general, the addition of iron has been shown to enhance both the cytotoxicity and selectivity of the treatment, but not in all cell lines.10,15

AMDT is a sesquiterpene found in the hairy roots of A. annua. It has been demonstrated that it induces apoptosis through the mitochondrial dependent pathway in human lung 95-D cells. Cytotoxicity of this compound was also found in ovary, liver, and cervix cancer cells.16

No cross-resistance has been found between the artemisinin-related as well as the unrelated compounds, so cells resistant to one compound retain sensitivity to another one.17

Alleged indications

Apart from malaria, A. annua is also used in cases of fever, headaches, infections and inflammations.18 It has been claimed to kill cancer cells and to be especially effective in breast cancer and leukaemia.19,20

Prevalence

There are no data available on the prevalence of use of A. annua in the treatment of cancer.

Legal issues

There are no A. annua derived drugs that are approved for cancer treatment.

Cost(s) and expenditures

Prices available on the internet for artesunate range between US $0.30 and 0.70 for a 100mg tablet or capsule, i.e. the price for a one-month supply ranges from US$ 9 to 21 at a daily dose of 100mg.

Citation

Klara Rombauts, Arne Heyerick, CAM-Cancer Consortium. Artemisia annua [online document]. http://cam-cancer.org/The-Summaries/Herbal-products/Artemisia-annua. January 29, 2015.

Document history

Assessed as up to date in January 2015 by Barbara Wider.
Summary assessed as up to date in August 2013 by Barbara Wider.

Summary fully revised and updated in August 2012 by Klara Rombauts.

Summary first published in March 2011, authored by Klara Rombauts and Arne Heyerick.

References

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  3. Carbonara T, Pascale R, Argentieri MP, Papadia P, Fanizzi FP et al. Phytochemical analysis of a herbal tea of Artemisia annua L. J Pharm Biomed Anal 2012;62:79-86.
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  5. Weathers PJ, Towler MJ. The flavonoids casticin and artemetin are poorly extracted and are unstable in an Artemisia annua tea infusion. Planta Med 2012;78(10):1024-6.26. McGovern PE, Christofidou-Solomidou M, Wang W, Dukes F, Davidson T and El-Deiry WS. Anticancer activity of botanical compounds in ancient fermented beverages (review). Int J Oncol 2010;37:5-14.
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