Artemisinin Research

Holley Pharmaceuticals has collected about 300 articles on artemisinin from peer-reviewed academic publications and other reputable sources. The following are some scientific documents relating to the effects of artemisinin. This serves as a primary source of information and references for scientists and health professionals. Readers should refer to the original articles for details. 

This does not constitute a suggestion or an imply to take artemisinin for any diseases. Only qualified healthcare professionals can give you medical advices.

 

Artemisinin -  a compound extracted from the herb Artemisia annua L. 

SELECTED SCIENTIFIC DOCUMENTATIONS ON ARTEMISININ

Artemisinin

Artemisinin is a compound extracted from the plant Artemesia annua L. (sweet wormwood, also known as the Chinese herbal Qinghao). Artemisinin (C15H22O5 ) is a sesquiterpene lactone. Artemesia annua has been used in China since AD 341 to treat febrile illness. In 1971, the active ingredient, artemisininin, was identified and isolated.  (PM O’Neill, Univ. of Liverpool, WHO Report, No. 36, Malaria, Encouraging Results from Studies to Improve the Safety and Efficacy of Natural Drug Compounds. 2001)

Derivatives of artemisinin have been synthesized. These include: dihydroartemisinin (DHA), artemether, artesunate, arteether, and artelinic acid.  These compounds have been packaged in different forms: tablets, capsules, suppositories and injectibles. DHA, artesuante and artelinate are relatively water-soluble, whereas the others are oil (fat) – soluble. (Artemisinin Research Foundation website, 2002)

Mechanism of Action

The artemisinin molecule contains two oxygen atoms linked together in what is known as an ‘endoperoxide bridge’, which could react with an iron atom to form free radicals. Artemisinin is toxic to malaria parasites because the parasite contains a high amount iron in the form of heme molecules. (Zhang F., Gosser DK Jr. et al, Hemin-catalyzed decomposition of artemisinin (qinghao). Biochem Pharmacol 1992; 43: 1805-9.)

Free radicals cause to macromolecular damages and kill the parasites. Artemisinin has been used as an antimalaria in more than two millions patients. (Anderson KM et al, Free radicals and reactive oxygen species in programmed cell death. Med Hypotheses, 1999; 52: 451-63.)

Rapid growth abnormal cells sequester relatively large amount of iron mainly in the form of holotranferrin. Artemisinin has been shown to cause rapid and extensive damage to these abnormal cells and have reatively low toxicity to normal cells. (Dr. H. Lai and Dr. NP Singh, Dept. of Bioengineering, School of Medicine, University of Washington, USA, 2002 ).

Toxicity

Large Animals. When artemisinin was tested with monkeys, they showed no toxicity after they received up to 292 mg/kg of artemether over 1 to 3 months. High doses of artemisinin can produce neurotoxicity such as gait disturbances, loss of spinal and pain response, respiratory depression, and ultimately cardiopulmonary arrest in large animals. (Journal of Traditional Chinese Medicine 2(1): 31-36, 1982.)

 Healthy Volunteers. 250-mg artemisinin and artesunate were used in a pharmacokinetic studies. Both pharmaceutical forms were well-tolerated and no undesirable side effects were observed. (Benakis et al. Pharmacokinetics of artemisinin and artesunate after oral administrationi in healthy volunteers. American Journal of Tropical Medicine Hyg, Jan;56(1):17-23,1997.)

Mice. Artemisininin is virtually non-toxic (LD50 = 4228 mg/kg orally administered to mice) and without carcinogenicity. (Jung, Mankil and Schinazi, Raymond, Bioorganic & Medicinal Chemistry Letters, Vol. 4, No. 7; 931-934, 1994.)

Pharmacokinetics.

The healthy human voluntarily oral administrated 250 mg tablets of artemisinin and artesunate. For Artemisinin, the mean maximum drug concentration Cmax = 0.36 microgram/ml,  appearance half life T1/2  = 0.62 hr, distribution half life t1/2 á = 2.61 hr, decline half-life t1/2 â = 4.34 hr, total area under the concentration-time curve (AUC) = 1.19 microgram.hg/ml, its main metabolite, dihydroartemisinin was measurable in the plasma. For artesunate, half lives were much shorter. (Benakis, et al, Dept. of Pharmacology, Geneva U. Swiss, Am J Trop Med Hyg, Jan;56(1): 17-23, 1997.)

Reference List

  1. Beekman AC, Barentsen AR, Woerdenbag HJ, et al: Stereochemistry-dependent cytotoxicity of some artemisinin derivatives. J Nat Prod 60:325-330, 1997.

  2. Beekman AC, Wierenga PK, Woerdenbag HJ, et al: Artemisinin-derived sesquiterpene lactones as potential antitumour compounds: cytotoxic action against bone marrow and tumour cells. Planta Med 64:615-619, 1998.

  3. Beekman AC, Woerdenbag HJ, Van Uden W, et al: Stability of artemisinin in aqueous environments: impact on its cytotoxic action to Ehrlich ascites tumour cells. J Pharm Pharmacol 49:1254-1258, 1997.

  4. Bhisutthibhan J, Philbert MA, Fujioka H, Aikawa M, Meshnick SR: The Plasmodium falciparum translationally controlled tumor protein: subcellular localization and calcium binding. Eur J Cell Biol 78:665-670, 1999.

  5. Efferth T, Dunstan H, Sauerbrey A, et al: The anti-malarial artesunate is also active against cancer. Int J Oncol 18:767-773, 2001.

  6. Efferth T, Davey M, Olbrich A, et al.: Activity of drugs from traditional Chinese medicine toward sensitive and MDR1- or MDR1-overexpressing multidrug-resistant human CCRF-CEM leukemia cells. Blood Cells, Molecules, and Diseases 28:160-168, 2002.

  7. Efferth T, Olbrich A, Bauer R: mRNA expression profiles for the response of human tumor cell lines to the antimalarial drugs artesunate, arteether, and artemether. Biochem Pharmacol 64:617-623, 2002.

  8. Fishwick J, Edwards G, Ward SA, et al: Binding of dihydroartemisinin to differentiating neuroblastoma cells and rat cortical homogenate. Neurotoxicology 19:405-412, 1998.

  9. Fishwick J, Edwards G, Ward SA, et al: Morphological and immunocytochemical effects of dihydroartemisinin on differentiating NB2a neuroblastoma cells. Neurotoxicology 19:393-403, 1998.

  10. Hu YQ, Tan RX, Chu MY, et al: Apoptosis in human hepatoma cell line SMMC-7721 induced by water-soluble macromolecular components of Artemisia capillaris Thunberg. Jpn J Cancer Res 91:113-117, 2000.

  11. Lai H, Singh NP: Selective cancer cell cytotoxicity from exposure to dihydroartemisinin and holotransferrin. Cancer Lett 91:41-46, 1995.

  12. Lee CH, Hong H, Shin J, et al.: NMR studies on novel antitumor drug candidates, deoxoartemisinin and carboxypropyldeoxoartemisinin. Biochem Biophys Res Comm 274:359-369, 2000.

  13. Li Y, Shan F, Wu JM, et al: Novel antitumor artemisinin derivatives targeting G1 phase of the cell cycle. Bioorg Med Chem Lett 11:5-8, 2001.

  14. McLean WG, Ward SA: In vitro neurotoxicity of artemisinin derivatives. Med Trop (Mars) 58:28-31, 1998.

  15. Moore JC, Lai H, Li JR, et al: Oral administration of dihydroartemisinin and ferrous sulfate retarded implanted fibrosarcoma growth in the rat. Cancer Lett 98:83-87, 1995.

  16. Mukanganyama S, Widersten M, Naik YS, et al: Inhibition of glutathione S-transferases by antimalarial drugs possible implications for circumventing anticancer drug resistance. Int J Cancer 97:700-705, 2002.

  17. Posner GH, Ploypradith P, Parker MH, et al: Antimalarial, antiproliferative, and antitumor activities of artemisinin-derived, chemically robust, trioxane dimers. J Med Chem 42:4275-4280, 1999.

  18. Reungpatthanapong P, Mankhetkorn S: Modulation of multidrug resistance by artemisinin, artesunate and dihydroartemisinin in K562/adr and GLC/adr resistant cell lines. Biol Pharm Bull 25:1555-1561, 2002.

  19. Sadava D, Phillips T, Lin C, et al: Transferrin overcomes drug resistance to artemisinin in human small-cell lung carcinoma cells. Cancer Lett 179:151-156, 2002.

  20. Shaikenov TE, Adekenov SM, Williams RM, et al: Arglabin-DMA, a plant derived sesquiterpene, inhibits farnesyltransferase. Oncol Rep 8:173-179, 2001.

  21. Singh NP, Lai H: Selective toxicity of dihydroartemisinin and holotransferrin toward human breast cancer cells. Life Sci 70:49-56, 2001.

  22. Singh NP, Verma KB: Case report of a laryngeal squamous cell carcinoma treated with artesunate. Arch Oncol 10:279-280, 2002.

  23. Smith SL, Maggs JL, Edwards G, et al: The role of iron in neurotoxicity: a study of novel antimalarial drugs. Neurotoxicology 19:557-559, 1998.

  24. Sun WC, Han JX, Yang WY, et al: [Antitumor activities of 4 derivatives of artemisic acid and artemisinin B in vitro]. Zhongguo Yao Li Xue Bao 13:541-543, 1992.

  25. Woerdenbag HJ, Merfort I, Passreiter CM, et al: Cytotoxicity of flavonoids and sesquiterpene lactones from Arnica species against the GLC4 and the COLO 320 cell lines. Planta Med 60:434-437, 1994.

  26. Woerdenbag HJ, Moskal TA, Pras N, et al: Cytotoxicity of artemisinin-related endoperoxides to Ehrlich ascites tumor cells. J Nat Prod 56:849-856, 1993.

  27. Wu JM, Shan F, Wu GS, et al: Synthesis and cytotoxicity of artemisinin derivatives containing cyanoarylmethyl group. Eur J Med Chem 36:469-479, 2001.

  28. Zheng GQ: Cytotoxic terpenoids and flavonoids from Artemisia annua. Planta Med 60:54-57, 1994.

Artemisinin Pharmacology and Pharmacokinetics

  1. Dhingra V, Rao KV, Narasu NL: Current status of artemisinin and its derivatives as antimalarial drugs. Life Sci 66:279-300, 2000.

  2. Navaratnam V, Mansor SM, Sit NW, et al: Pharmacokinetics of artemisinin-type compounds. Clin Pharmacokinet 39:255-270, 2000.

Full or more articles are available upon request. Please email to manager@holleypharma.com

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