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Artemisia absinthium: a forgotten antimalarial

December 20, 2012 - 14:51 -- Pierre Lutgen

 

Artemisia afra, Artenmisia herba alba, Artemisia sieberi, Artemisia absinthium have been and are still widely used as antimalarials. Some of them contain molecules like luteolin, santonin or nerolidol which have properties equivalent to quinine. They all contain a broad range of essential oils, polyphenols, coumarins, polysaccharides, saponins which differ from species to species. But the question remains : what could be a common constituent which raises the antimalarial efficiency of these plants above others. 
 
It appears that α-thujone and β-thujone represent the major constituent of all these artemisia varieties, sometimes more than 50% of the total essential oil.
 
Evidence that thujone is the active antimalarial molecule in many artemisia species is confirmed in a recent paper from the Pasteur Institute of Iran. Artemisia absinthium extract has an antiplasmodial IC50 of 0.19 µg/mL vs 0.40 for chloroquine . But Artemisia dracunculus which contains no thujone  has no noticeable antimalarial activity ( >200 µg/mL). Artemisia vulgaris and Artemisia khorassanica  contain small quantities of thujone and show moderate antiplasmodial activities.
 
A recent finding of the Universities of Leiden and Liege  supports the thujone hypothesis. The apolar fractions of both Artemisia afra and Artemisia annua showed activity against P. falciparum while activity was only found in the tea infusion of Artemisia annua. Thujone is insoluble in water. To take full advantage of the essential oil thujone which is not water soluble, it is thus preferable to administer the plant, not in the form of an infusion, but as dry powder in capsules or to work with a chloroform extract.
 
Other plants like wild sage (Salvia officinalis) contain large amounts of thujone and are potential anti-malarial drugs. Their essential oils have excellent anti-inflammatory properties (1) .
 
The University  of Al Quds (2), Jerusalem, has shown that thujone prevents the formation of β-hematin (hemozoin), which is also the key mechanism for  quinine. Thujone also leads to an augmentation of the humoral and cell mediated immune (3)  responses. The molecule is well known for its bactericidal and vermicidal properties. This may explain why Artemisia herba alba is extensively used in Algeria against the severe inflammatory disease Adamiantides-Behçet (4) .The University of Leiden has found remarkable anti-HIV activity for Artemisia afra (5) . A German research team found that the administration of Artemisia absinthium powdered herbal substance in the form of 500 mg capsules  for the treatment of Crohn’s disease, at week 10,  65% of the patients were almost free of  the disease symptoms compared to none in the placebo group (6) .
 
The first study on the antimalarial effect of Artemisia absinthium was published in 1990 (7)  .  The highest suppression  (96%) of Plasmodium berghei infected mice was observed with the ethanolic extract given orally in a concentration of 74 mg/kg.  Antiplasmodial effects of Artemisia absinthium have also been noticed by a research group in Cuba (8)  in cooperation with the University of Antwerpen. Already in 2003 it had been confirmed that lipophilic extracts from Artemisia afra were more active than the extracts of 8 other plants from Zimbabwe(9).
 
In a recent study (11)  the hydro-ethanolic extract of 5 Artemisia species were screened for their antiplasmodial and toxicity properties (A absinthium, A scoparia, A annua, A vulgaris, A dracunculus).  A. annua and A absinthium showed the best activity in vitro and also reduced parasitemia in vivo in female BALB/C mice,. A absinthium was up to 64 times more potent than A annua. This is probably related to the essential oils  present in A absinthium. All five species analyzed contain the common flavonoids present in the Artemisia genus. A similar study in 1991 (12) already had shown the in vitro and in vivo that A absinthium acted more potently than A annua.
 
Several of these research groups have investigated potential toxicities of thujone and found none or little. The product even has hepatoprotective properties (10). This was confirmed in the above study (11).
 
Thujone which was banned in Europe for hundred years is now again available since 10 years, as food additive, in legal quantities. History has ups and downs. The French after the conquest of Algiers in 1830 used the plant as antimalarial for hundred years, eventually based on Artemisia herba alba which is endemic in the Maghreb.  All these plants containing thujone make an exponential come-back,from the Artemisia absinthium of our grand-mothers to Artemisia afra. Until the year 2000 only 3 scientific papers had been published concerning this plant; over the last ten years more than 100.
 
 1. GA Noqueira de Melo et al., J of Med Plants Res., 6(35) 2112, 4934-39
 2. M Akkawi et al., Malaria Journal, 2012, 11 (Suppl1), p3.
 3. KS Siveen et al., International Immunopharmacogy, o6, 2011, 1967-75.
 4. D Messaoudene et al., Journal of Inflammation, 2011, 8 :35 
 5.  A.Lubbe, I Seibert, T Klimhait, Fr van der Kooy, Journal of Ethnopharmacology, Accepted 15 Mar 2012.
 6. B Omer et al., Phytomedicine, 14 (2007) 87-95
 7. M.M. Zahar et al Journal of Ethnopharmacology 1990 Sep.30 (2), 223-6.
 8. Aymé Fernández-Calienes Valdés et al., Mem Inst Oswaldo Cruz, Rio de Janeiro, Vol. 103(6): 615-618, Sep 2008 615
 9. C Kraft et al., Phytotherapy Research, 17,2, 2003, 123-128
 10. N Nahrevanian et al., Iranian J Parasitol 5,1, 2010, 6-19.
 11. A Ramazani, S Sardari et al., Parasitol Res 18 May 2010
 12 P Misra et al., Pharm Biol. 29, 1991, 19-23
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