Artemisia annua

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Artemisia annua

Common Names

  • Qing Hao
  • Sweet sagewort
  • Sweet wormwood
  • Annual wormwood

For Patients & Caregivers

How It Works

A compound from artemisia is used as part of combination therapy to treat malaria, but studies of its use for other conditions are limited.

Artemisia annua is an herb traditionally used in Chinese medicine to treat fever, inflammation, and malaria. A compound from artemisia is used in combination with other drugs to treat malaria.

There are limited studies on the use of artemisia or it compounds for other conditions. A few initial studies suggest it may help treat osteoarthritis. Other preliminary studies in advanced cancer patients have not shown any clinical response, and patients need to be monitored for potential side effects. More studies are needed to determine whether compounds from artemisia are safe and effective for these conditions.

Purported Uses
  • To treat malaria
    A compound from artemisia is used in combination with other drugs to treat malaria. Patients need to be treated by a healthcare provider for this condition, and should not self-treat with artemisia for malaria.
  • To reduce inflammation
    Preliminary studies suggest that artemisia may be helpful for hip or knee osteoarthritis, but more study is needed.
  • To treat cancer
    Only a few safety studies in advanced cancer patients have been conducted, and have not shown a treatment response. In addition, patients need to be monitored for potential side effects. More studies are needed to determine the conditions under which compounds derived from artemisia may be safe and effective.
Side Effects

Case reports

  • Hepatitis: One case was attributed to an herbal supplement containing artemisinin. Another case was linked to drinking artemisia tea to protect against malaria.
  • Anemia: Two cases of loss of healthy red blood cells after artemisinin-based treatment for malaria.
  • Hearing loss, ringing in the ears, and dizziness: Among several advanced breast cancer patients in a safety trial, and possibly related to oral artesunate, an active artemisia compound. The study drug was otherwise largely well tolerated among patients.
  • Skin rash: With topical use of artemisia.
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For Healthcare Professionals

Scientific Name
Artemisia annua
Clinical Summary

Commonly known as wormwood or sweet sagewort, Artemisia annua has been used in traditional Chinese medicine for fevers, inflammation, headaches, bleeding, and 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). Cytotoxic effects of A. annua compounds have also been evaluated in tumor cell lines (1) (18) (19) (20) (25) (26).

Artemisinin-based combination therapies are part of the standard treatment arsenal for malaria. Systematic reviews have shown it to be as effective as quinine for both uncomplicated and severe malaria (4) (5), but increased risk of relapse may limit its uses (6) (7). It is also unclear whether it is effective against quinine-resistant malaria strains. Other reports of artemisinin-based therapy resistance are also emerging, prompting additional drug development (28). Large superiority trials of artemisia tea infusions found them equivalent or superior to artesunate-amodiaquine against malaria (29) and effective against schistosomiasis compared with standard praziquantel treatment (30).

Studies of artemisia for other conditions are limited. In one RCT, a low-dose artemisia formulation produced clinically relevant pain reductions in patients with hip or knee osteoarthritis (3). A subsesquent open-label continuation study demonstrated long-term safety with maintained improvements at 6 months (10). A few safety studies in advanced cancer patients suggest oral add-on artesunate, a semisynthetic artemisinin derivative, is well tolerated, although monitoring for ototoxicity is needed (13) (21). In other studies, oral or intravenous artesunate did not produce a response (31) (32), although modest clinical activity was observed with intravenous administration (32). More studies are needed to determine the conditions under which compounds derived from artemisia may be safe and effective.

Purported Uses
  • Malaria
  • Inflammation
  • Cancer
Mechanism of Action

Artemisinin, the active constituent of A. annua, exerts antimalarial effects by free radicals formed via cleavage of the endoperoxide bond in its structure, which are responsible for eradicating the Plasmodium species (23).

Artemisinin induces apoptosis and cell cycle arrest of Leishmani donovani promastigotes (8). It 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 G1 cell-cycle arrest in neuroblastoma cell lines (25). Dihydroartemisinin, a semi-synthetic derivative of artemisinin, demonstrates anti-inflammatory activity by attenuating COX-2 production via downregulation of serine/threonine kinase (AKT) and mitogen activated protein kinase (MAPK) pathways  (24). Recent findings suggest that dihydroartemisinin-triggered apoptosis in colorectal cells occurs through the reactive oxygen species (ROS)-mediated mitochondria-dependent pathway (26).

Contraindications
  • Patients with ulcers or gastrointestinal disorders should not take artemisia (11).
Adverse Reactions

Case reports

  • Hepatitis: In a 52-year-old man following consumption of an herbal supplement containing artemisinin (17).
  • Acute cholestatic hepatitis: In a patient due to ingestion of artemisia tea as prophylaxis against malaria (33).
  • Delayed hemolytic anemia: Two cases after either oral or intravenous therapy with artemisinin-based treatment for malaria (34) (35). It is thought this reaction may be related to higher parasite loads (34).
  • Ototoxicity and vertigo: Possibly related to oral artesunate, an active artemisia compound, among several advanced breast cancer patients in a safety trial (13) (21). The study drug was otherwise largely well tolerated among patients.
  • Dermatitis: With topical use of artemisia (11).
Herb-Drug Interactions
  • Cytochrome P450 (CYP450) substrates: In laboratory studies, artemisia extracts induced CYP2B6 and CYP3A4 (27) and may affect the serum concentration of drugs metabolized by these enzymes. Clinical relevance has yet to be determined.
Dosage (OneMSK Only)
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. Stebbings S, Beattie E, McNamara D, et al. A pilot randomized, placebo-controlled clinical trial to investigate the efficacy and safety of an extract of Artemisia annua administered over 12 weeks, for managing pain, stiffness, and functional limitation associated with osteoarthritis of the hip and knee. Clin Rheumatol. Jul 2016;35(7):1829-1836.
  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. Hunt S, Stebbings S, McNamara D. An open-label six-month extension study to investigate the safety and efficacy of an extract of Artemisia annua for managing pain, stiffness and functional limitation associated with osteoarthritis of the hip and knee. N Z Med J. Oct 28 2016;129(1444):97-102.
  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. Konig M, von Hagens C, Hoth S, et al. Investigation of ototoxicity of artesunate as add-on therapy in patients with metastatic or locally advanced breast cancer: new audiological results from a prospective, open, uncontrolled, monocentric phase I study. Cancer Chemother Pharmacol. Feb 2016;77(2):413-427.
  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 July 9, 2020.
  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. Konig M, von Hagens C, Hoth S, et al. Erratum to: Investigation of ototoxicity of artesunate as add-on therapy in patients with metastatic or locally advanced breast cancer: new audiological results from a prospective, open, uncontrolled, monocentric phase I study. Cancer Chemother Pharmacol. Jun 2016;77(6):1321.
  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.
  27. Xing J, Kirby BJ, Whittington D, et al. Evaluation of P450 inhibition and induction by artemisinin antimalarials in human liver microsomes and primary human hepatocytes. Drug Metab Dispos. 2012 Sep;40(9):1757-64.
  28. van der Pluijm RW, Tripura R, Hoglund RM, et al. Triple artemisinin-based combination therapies versus artemisinin-based combination therapies for uncomplicated Plasmodium falciparum malaria: a multicentre, open-label, randomised clinical trial. Lancet. Apr 25 2020;395(10233):1345-1360.
  29. Munyangi J, Cornet-Vernet L, Idumbo M, et al. Artemisia annua and Artemisia afra tea infusions vs. artesunate-amodiaquine (ASAQ) in treating Plasmodium falciparum malaria in a large scale, double blind, randomized clinical trial. Phytomedicine. Apr 2019;57:49-56.
  30. Munyangi J, Cornet-Vernet L, Idumbo M, et al. Effect of Artemisia annua and Artemisia afra tea infusions on schistosomiasis in a large clinical trial. Phytomedicine. Dec 1 2018;51:233-240.
  31. von Hagens C, Walter-Sack I, Goeckenjan M, et al. Long-term add-on therapy (compassionate use) with oral artesunate in patients with metastatic breast cancer after participating in a phase I study (ARTIC M33/2). Phytomedicine. Feb 15 2019;54:140-148.
  32. Deeken JF, Wang H, Hartley M, et al. A phase I study of intravenous artesunate in patients with advanced solid tumor malignancies. Cancer Chemother Pharmacol. Mar 2018;81(3):587-596.
  33. Ruperti-Repilado FJ, Haefliger S, Rehm S, et al. Danger of Herbal Tea: A Case of Acute Cholestatic Hepatitis Due to Artemisia annua Tea. Front Med (Lausanne). 2019;6:221.
  34. Conlon CC, Stein A, Colombo RE, et al. Post-artemisinin delayed hemolysis after oral therapy for P. falciparum infection. IDCases. 2020;20:e00741.
  35. Hasegawa C, Kudo M, Maruyama H, et al. Severe delayed haemolytic anaemia associated with artemether-lumefantrine treatment of malaria in a Japanese traveller. J Infect Chemother. Mar 2018;24(3):216-219.
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