Artemisia annua

Health Care Professional Information

Scientific Name
Artemisia annua
Common Name

Qing Hao, sweet sagewort, sweet wormwood, annual wormwood

Clinical Summary

Commonly known as wormwood or sweet sagewort, Artemisia annua has been used in traditional Chinese medicine for reducing fevers, inflammation, headaches, bleeding and for treating malaria.

In vitro studies indicate that artemisinin, the active principle of A. annua, may be an effective treatment for protozoal infections including leishmaniasis (8), Chagas' disease, and African sleeping sickness (9).
Systematic reviews of artemisinin show that it is as effective as quinine in treating both uncomplicated and severe malaria (4) (5). However, increased risk of relapse may limit its uses (6) (7). It is also unclear whether A. annua is effective against strains of malaria that are resistant to quinine.
A study done in a rat model suggests that A. annua may have contraceptive effects (21).

A. annua has also been investigated for its anticancer properties. Terpenoids and flavonoids isolated from the herb exert cytotoxic effects in several human tumor cell lines (1) (18) (19) (20). Two of the components, artemisinin and artesunate, have been studied as anticancer treatments.

Purported Uses
  • Cancer treatment
  • Fever
  • Headaches
  • Infections
  • Inflammation
  • Malaria
Constituents
  • Artemisinin
  • Caffeic Acid derivatives
  • Flavanoids
  • Coumarins
  • Terpenes
    (22)
Mechanism of Action

Artemisinin exerts anti-malarial effects by free radicals formed via cleavage of the endoperoxide bond in its structure, which are responsible for eradicating Plasmodium species (23). In addition to antimalarial effects, artemisinin also effectively induces apoptosis and cell cycle arrest of Leishmani donovani promastigotes (8).
Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, demonstrates anti-inflammatory activity by attenuating COX-2 production via down-regulation of serine/threonine kinase (AKT) and mitogen activated protein kinase (MAPK) pathway (24).

Artemisinin also has antiproliferative effects on medullary thyroid carcinoma cells (2), and induces apoptosis in a lung cancer cell line by modulating p38 and calcium signaling (14). In another study, it significantly inhibited cell growth and proliferation, and caused cell cycle arrest in the G1 phase in neuroblastoma cell lines (25). Recent findings suggest that dihydroartemisinin-triggered apoptosis in colorectal cells occurs through the reactive oxygen speciies (ROS)-mediated mitochondria-dependent pathway (26).

Pharmacokinetics

Absorption: Artemisinin is absorbed faster from the tea preparations than from capsules. The maximum plasma concentrations were observed after 30 minutes following intake (15). Artesunate is rapidly absorbed and reaches maximum plasma level within 45-90 minutes. It is metabolized in the liver by hydrolysis to dihydroartemisinin (16).

Contraindications
  • Patients with ulcers or gastrointestinal disorders should not take Artemisia (11).
Adverse Reactions
  • A case of hepatitis was reported following consumption of a herbal supplement containing artemisinin (17).
  • Topical use of artemisia may cause dermatitis (11).
Herb-Drug Interactions
  • Antiseizure medications: Artemisia can induce seizures resulting in decreased efficacy of antiseizure medications (11).
Literature Summary and Critique

Blanke CH, et al. Herba Artemisiae annuae tea preparation compared to sulfadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria in adults: a randomized double-blind clinical trial. Trop Doct. Apr 2008;38(2):113-116.
In order to compare the efficacy and safety of Artemisia annua herb compared to sulfadoxine-pyrimethamine for the treatment of malaria induced by Plasmodium falciparum, 13 participants received 5 or 9 g Artemisia annua/L/day + placebo tablet and 10 received sulfadoxine-pyrimethamine (25 mg/kg sulfadoxine and 1.25 mg/kg pyrimethamin) + placebo tea 3.5 g Radix Gentianae/L/day. Clinical symptoms and adverse events were recorded along with the parasitological cure rates. The number of adverse events was similar between the treatment groups. Although the 7-day cure rate was similar between the groups, more failures were seen in the group receiving Artemisia annua after 28 days. Because insufficient treatment and thus incomplete cure is thought to select for treatment-resistant organisms, Artemisia annua herb monotherapy for malaria is not advised.

Mueller MS, et al. Randomized controlled trial of a traditional preparation of Artemisia annua L. (Annual Wormwood) in the treatment of malaria. Trans R Soc Trop Med Hyg. 2004 May;98(5):318-21.
132 patients were randomly assigned to receive 5 grams of artemisia annua herb/L (1 liter/day for 7 days); 9 grams of artemisia annua herb /L (1 liter/day for 7 days); and quinine sulphate tablets (500 mg quinine sulphate, three times daily for 7 days). There was quick resolution of parasitaemia and clinical symptoms following 7 days of treatment. Although the cure rates were 74% with artemisia compared with 91% for quinine, researchers conclude that artemisia cannot be recommended as a substitution for quinine because symptoms reappeared at much faster rates in artemisia groups. It is unclear whether artemisia annua is effective against strains of malaria that are resistant to quinine. Further investigation is warranted.

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References
  1. Singh NP, Lai HC. Artemisinin induces apoptosis in human cancer cells. Anticancer Res. 2004 Jul-Aug;24(4):2277-80.
  2. Zheng GQ. Cytotoxic terpenoids and flavonoids from Artemisia annua. Planta Med. 1994 Feb;60(1):54-7.
  3. Bensky D, Gamble A. Chinese Herbal Medicine, Materia Medica. Seattle: Eastland Press, Inc 1993.
  4. McIntosh HM, Olliaro P. Artemisinin derivatives for treating severe malaria. Cochrane.Database.Syst.Rev. 2000;CD000527.
  5. McIntosh HM, Olliaro P. Artemisinin derivatives for treating uncomplicated malaria. Cochrane.Database.Syst.Rev. 2000;CD000256.
  6. Mueller MS, et al. Randomized controlled trial of a traditional preparation of Artemisia annua L. (Annual Wormwood) in the treatment of malaria. Trans.R.Soc Trop.Med Hyg. 2004;98:318-21.
  7. Blanke CH, Naisabha GB, Balema MB, et al. Herba Artemisiae annuae tea preparation compared to sulfadoxine-pyrimethamine in the treatment of uncomplicated falciparum malaria in adults: a randomized double-blind clinical trial. Trop Doct. Apr 2008;38(2):113-116.
  8. Sen R, Bandyopadhyay S, Dutta A, et al. Artemisinin triggers induction of cell-cycle arrest and apoptosis in Leishmania donovani promastigotes. J Med Microbiol. Sep 2007;56(Pt 9):1213-1218.
  9. Mishina YV, Krishna S, Haynes RK, Meade JC. Artemisinins inhibit Trypanosoma cruzi and Trypanosoma brucei rhodesiense in vitro growth. Antimicrob Agents Chemother. May 2007;51(5):1852-1854.
  10. Brinker F. Herb Contraindications And Drug Interactions. Sandy, OR: Eclectic Medical Publications, 2001.
  11. Skyles AJ, Sweet BV. Alternative therapies. Wormwood. Am J Health Syst.Pharm. 2004;61:239-42.
  12. Rinner B, et al. Activity of novel plant extracts against medullary thyroid carcinoma cells. Anticancer Res 2004;24:495-500.
  13. Huang KC. The Pharmacology of Chinese Herbs, Second Edition. Boca Raton (FL): CRC Press; 1999.
  14. Mu D, Zhang W, Chu D, et al. The role of calcium, P38 MAPK in dihydroartemisinin-induced apoptosis of lung cancer PC-14 cells. Cancer Chemother Pharmacol. Apr 2008;61(4):639-645.
  15. Rath K, et al. Pharmacokinetic study of artemisinin after oral intake of a traditional preparation of Artemisia annua L. (annual wormwood). Am J Trop.Med Hyg. 2004;70:128-32.
  16. Payne AG. Exploiting intracellular iron and iron-rich compounds to effect tumor cell lysis. Med Hypotheses 2003;61:206-9.
  17. Centers for Disease Control and Prevention. Hepatitis Temporally Associated with an Herbal Supplement Containing Artemisinin —- Washington, 2008. Accessed May 11, 2011.
  18. Lai H, Nakase I, Lacoste E, Singh NP, Sasaki T. Artemisinin-transferrin conjugate retards growth of breast tumors in the rat. Anticancer Res. 2009 Oct;29(10):3807-10.
  19. Willoughby JA Sr, Sundar SN, Cheung M, et al. Artemisinin blocks prostate cancer growth and cell cycle progression by disrupting Sp1 interactions with the cyclin-dependent kinase-4 (CDK4) promoter and inhibiting CDK4 gene expression. J Biol Chem. 2009 Jan 23;284(4):2203-13.
  20. Zhai DD, Supaibulwatana K, Zhong JJ. Inhibition of tumor cell proliferation and induction of apoptosis in human lung carcinoma 95-D cells by a new sesquiterpene from hairy root cultures of Artemisia annua. Phytomedicine. 2010 Sep;17(11):856-61.
  21. Abolaji AO, Eteng MU, Ebong PE, Dar A, Farombi EO, Choudhary MI. Artemisia annua as a possible contraceptive agent: a clue from mammalian rat model. Nat Prod Res.2014 Dec;28(24):2342-6.
  22. van der Kooy F, Sullivan SE. The complexity of medicinal plants: the traditional Artemisia annua formulation, current status and future perspectives.J Ethnopharmacol. 2013 Oct 28;150(1):1-13.
  23. Ho WE, Peh HY, Chan TK, Wong WS. Artemisinins: pharmacological actions beyond anti-malarial. Pharmacol Ther. 2014 Apr;142(1):126-39.
  24. Kim HG, Yang JH, Han EH, et al. Inhibitory effect of dihydroartemisinin against phorbol ester-induced cyclooxygenase-2 expression in macrophages.  Food Chem Toxicol. 2013 Jun;56:93-9.
  25. Zhu S, Liu W, Ke X, et al. Artemisinin reduces cell proliferation and induces apoptosis in neuroblastoma. Oncol Rep. 2014 Sep;32(3):1094-100.
  26. Lu M, Sun L, Zhou J, Yang J.Dihydroartemisinin induces apoptosis in colorectal cancer cells through the mitochondria-dependent pathway. Tumour Biol. 2014 Jun;35(6):5307-14.

Consumer Information

How It Works

Bottom Line: Artemisia has been shown to be effective in the treatment of malaria.

Artemisia annua is an herb traditionally used in Chinese medicine to treat fever, inflammation, and malaria. A compound in artemisia was shown to be effective in treating malaria in a clinical trial. Another case study showed that artemisia was effective in treating chronic bladder infection. Artemisia prevented cancer cells from dividing in laboratory studies but clinical trials have not been conducted to support this.

Purported Uses
  • To treat malaria
    Several clinical trials support this use, however recurrence is more likely than with conventional antimalarial treatment.
  • To reduce inflammation
    No scientific evidence supports this use.
  • To reduce fever
    This use has not been evaluated in scientific studies.
  • To treat bacterial infections
    There are no data to back this claim.
  • To treat headache
    No scientific evidence supports this use.
  • To treat cancer
    Laboratory studies have shown some effect. Human data are lacking.
Research Evidence

Treatment of malaria
This study compared low-dose and high-dose artemisia with sulfadoxine-pyrimethamine (another conventional malaria treatment) for the treatment of malaria in 13 patients. The three groups had similar numbers of cures and failures after 7 days of treatment. And symptoms reappeared more quickly and in greater numbers in the artemisia group. Therefore, artemisia may not be effective against malaria.

In another clinical trial for the treatment of malaria, 132 patients were assigned to three test groups. Each group received either low-dose artemisia, high-dose artemisia or quinine (a conventional treatment for malaria). After 7 days of treatment, there were no symptoms of malaria in any of the three groups. Although artemisia was found to be as effective as quinine, researchers suggest that artemisia should not be used to treat malaria because symptoms reappeared at much faster rates in the artemisia group. It is unclear whether artemisia is effective against strains of malaria that are resistant to quinine.

Do Not Take If
  • You are taking antiseizure medications (artemisia can induce seizures making such medications less effective).
Side Effects
  • A case of hepatitis was reported following consumption of a herbal supplement containing artemisinin.
  • Topical use of artemisia may cause dermatitis.
E-mail your questions and comments to aboutherbs@mskcc.org.