Artemisia annua -Artemisia

Description

This aromatic annual herbaceous plant grows 1 - 2.4 m tall and is harvested in the fall. The stem is cylindrical and branched. Leaves are alternate, dark green or brownish green. Odour is characteristic and aromatic while the taste is bitter. It is characterized by large panicles of small globulous capitulums (2 - 3 mm diameter), with a whitish involucre, and by pinnatisect leaves which disappear after the blooming period. Small (1 - 2 mm) pale yellow flowers appear in mid-September and have a pleasant odor.
Indigenous to Asia, and cultivated in several provinces in China, it has been widely introduced into North America as a fragrant ornamental. It also grows wild in central and southern Europe.

Part Used

Dried aerial part.

Constituents

Considerable variation occurs in the chemical composition of the essential oil, according to origin.(1) This species of Artemisia contains abrotamine, beta-bourbonene, farnesyl acetate, camphene, isoartemisia ketone, caryophyllene, beta-humulene, episilon-cadinene, delta-cadinene, alpha-pinene, beta-pinene, camphene, limonene, 1,8-cincole, artemisia ketone, alpha-thujone, copaene, gamma-cadinene, and vitamin A.(2) Additional substances include 1-pinene, coumarin, stigmasterol, camphor, arteannuin A and B, artemisinic acid, and benzyl isovalerate.(3) Artemisinin, a sesquiterpene lactone, occurs in aerial parts in concentrations ranging from 0.01 to 1%. Cultivation and cloning is anticipated to increase this ratio to 2%.(4-6)

Mode of Action

The best known pharmacologically active compounds are found in the aerial part. Initial research with aqueous extracts of this plant during the 1960`s did not confirm traditional antimalarial properties however, subsequent testing of ethyl ether extracts were more promising. The result has been the discovery of a chemical entity called qinghaosu or artemisinin, a particularly promising antimalarial in an era where quinine and chloroquine-resistant malarial strains in southeast Asia are causing increasing concern. In one study using human subjects artemisinin reverse malaria symptoms in 100% of the 2099 patients infected. Artemisinin, which is only slightly water-soluble, is one of the few naturally occurring endoperoxides, and extensive study for twenty years has confirmed its ability to relieve malarial symptoms and eliminate the parasite faster than chloroquine. Crossing the blood-brain barrier, it is effective in cerebral malaria.(7) It has therefore been described as ``the first important new antimalarial agent of natural origin since the discovery of quinine.``(8,9) Artemisinin is probably formed via arteanniun B and artemisitene, by oxidation and lactonization of a sesquiterpene with a cadinane skeleton such as arteannuic acid. More recent research postulates artemisinic acid as artemisinin`s major precursor.(10,11)

It is a schizonticide, killing the asexual phase of the malarial Plasmodium when it inhabits the erythrocyte, thus curing, not just preventing malarial infestation. The mechanism is still debated but it is thought to be based on some kind of peroxidation or destabilization of the parasite cell membrane. Other authors suggest that artemisinin blocks the plasmodium`s utilization of host erythrocyte protein, starving it to death.(12) Yet another model suggests interaction with the iron in haem resulting from hemoglobin digestion by the parasite.(13) Synthetic derivatives are also being developed and tested. Since no resistance to artemisinin has been spotted in malarial strains to date, careful medical control is being applied to avoid encouraging resistance through preventive use.(14) More recent veterinarian research suggests that artemisia and artemisinin offer significant protection for poultry against Coccidia infestation. By inference, they may also have a role in humans in coccidiosis and schistosomiasis.(15-17)

Artemisinin enhances macrophage phagocytosis in mice. This herb, like most Artemisias is very effective against worms, with reduction 80 - 90% within a week.(18)

Therapeutic Action

Antibiotic, antimalarial, anticoccidial, antischistosomial.

Energetics

Traditional Chinese

Properties of qing hao are bitter and cold, entering the Kidney, Liver, and Gallbladder channels. It is noted for clearing summerheat, clearing fevers from deficiency, cooling blood and stopping nosebleeds, and for checking malarial disorders and relieving heat.(19)

Folklore

First appearing in the Divine Husbandman`s Classic of the Materia Medica,(20) this species of artemisia has been used for over 2,000 years for cases of malaria and febrile disorders. A review of its historical appearance in the broader history of malarial treatment has been published. Used to ‘resolve summer heat`, this herb was often employed to keep its users cool on hot summer days. (21)

Dosage

Raw Herb - 3 - 9 g, (up to 24 g for stronger effect)(22)
Artemisinin(e) - 100 mg tabs (1 g loading dose for malaria)(23)

Toxicity and Contraindications

Toxicity information appears primarily for the extracted endoperoxide, artemisinin, and confirms low toxicity and the virtual absence of side effects.(24) The median LD50 for mice is 4228 mg/kg (oral) and 3840 mg/kg for oil suspension. Subsequent research with other species suggests that acute toxicity of artemisinin is considerably less than chloroquine.(25) Use of artemisinin and its derivatives by pregnant women for malaria in uncomplicated cases is proscribed.(26,27)

Official Recognition and Medical References

Chinese mainland - antimalarial drug(28)

References

1. Bruneton, J., Pharmacognosy, Phytochemistry, Medicinal Plants. Intercept Ltd. Andover UK, 1995, p. 506-508.
2. Bensky, D. and A. Gamble, Chinese Herbal Medicine: Materia Medica (Revised Edition), Eastland Press, Seattle, WA, 1993, p. 110-11.
3. Qinghaosu, The Lawrence Review of Natural Products, Vol. 6, No.11, (1985), p. 1-3.
4. Bruneton, J., Ibid.
5. Van Geldre, E., et al., State of the art of the production of the antimalarial compound artemisinin in plants, Plant Mol. Biol., 1997, Jan; 33 (2): 199-209.
6. Tang, W. and G. Eisenbrand, Chinese Drugs of Plant Origin: Chemistry, Pharmacology, and Use in Traditional and Modern Medicine, Springer-Verlag, Berlin, 1992, p. 160.
7. Evans, W.C., Trease and Evans` Pharmacognosy (14th Edition), WB Saunders Co. Ltd, London, 1996, p. 326.
8. Qinghaosu, The Lawrence Review of Natural Products, Ibid.
9. Woerdenbag, H.J., et al., Progress in the research of artemisinin-related
10. Kohler, M., et al., Extraction of artemisinin and artemisinic acid from Artemisia annua L. using supercritical carbon dioxide. J. Chromatogr A 1997, Oct 17; 785(1-2):353-60
11. Huang, K.C., The Pharmacology of Chinese Herbs, CRC Press, Boca Raton, FL, 1993, p. 344.
12. Huang, K.C., The Pharmacology of Chinese Herbs, CRC Press, Boca Raton, FL, 1993, p.344.
13. Evans, W.C., Trease and Evans` Pharmacognosy (14th Edition), WB Saunders
Co. Ltd, London, 1996, p. 428.
14. Bruneton, J., Ibid.
15. Allen, P.C., et al., Effects of components of Artemisia annua on coccidia infections in chickens, Poult Sci 1997 Aug; 76 (8): 1156-63.
16. Huang, K.C., Ibid.
17. Tang, W. and G. Eisenbrand, Chinese Drugs of Plant Origin: Chemistry, Pharmacology, and Use in Traditional and Modern Medicine, Springer-Verlag, Berlin, 1992, p.171.
18. Tang Ibid
19. Bensky, D. and A. Gamble, Ibid.
20. Bensky, D. and A. Gamble, Ibid.
21. Dobson, M.J., Bitter-sweet solutions for malaria: exploring natural remedies from the past. Parassitologia 1998 Jun; 40 (1-2): 69-81.
22. Bensky, D. and A. Gamble, Ibid.
23. Huang, K.C., The Pharmacology of Chinese Herbs, CRC Press, Boca Raton, FL, 1993, p. 343.
24. Tang, W. and G. Eisenbrand, Chinese Drugs of Plant Origin: Chemistry, Pharmacology, and Use in Traditional and Modern Medicine, Springer-Verlag, Berlin, 1992, p. 167.
25. Qinghaosu, The Lawrence Review of Natural Products, Ibid.
26. Bruneton, J., Ibid.
27. McGuffin, M., et al., American Herbal Products Association`s Botanical Safety Handbook, CRC Press, Boca Raton, FL, 1997, p. 15.
28. Tang, W. and G. Eisenbrand, Chinese Drugs of Plant Origin: Chemistry,
Pharmacology, and Use in Traditional and Modern Medicine, Springer-Verlag, Berlin, 1992, p. 159.