The species of wormwood known as Artemisia annua has been used in Traditional Chinese Medicine for the treatment of fevers and malaria for many centuries. The active antimalarial compound known as artemisinin was isolated by Chinese researchers in the early 1970s. Since then research has focussed on artemisinin and its semi-synthetic derivatives such as artemether and artesunate. These drugs have become established as safe and effective antimalarial drugs which have particular value in the treatment of chloroquine-resistant parasites. However, a group of German scientists (1) have focussed their research effort on the use of the whole herb, particularly when taken as an infusion with boiling water. The motivation behind this research is to understand the value of the traditional use of Artemisia annua for the treatment of malaria, because this application could readily be adopted in poor countries such as in Africa where the semi-synthetic drugs are relatively expensive.
Artemisia annua can be cultivated with relative ease and there are new hybrids than can yield up to 1% artemisinin. One of the questions which needed to be answered was whether an infusion of the herb can deliver significant quantities of artemisinin into the bloodstream. Fourteen healthy male volunteers received 1 liter of tea prepared from 9g of Artemisia annua leaves. Blood samples were taken and artemisinin was measured by HPLC. Significant quantities of the phytochemical were found in the plasma. Artemisinin was absorbed faster from the herbal tea than from oral solid dosage forms, but its bioavailability was similar. The 1 liter of tea (from 9g of Artemisia annua) contained 94.5mg of artemisinin, which is approximately one-fifth of the usually recommended daily dose. The authors concluded that artemisinin plasma concentrations after intake as an herbal tea are sufficient for clinical effects, but insufficient to recommend such preparations as equivalent substitutes for modern artemisinin-based drugs in malaria therapy.
The same research team also investigated the clinical efficacy of an Artemisia annua tea in the treatment of subacute malaria in Africa. (2) In an uncontrolled study, 48 patients received the tea for 4 days (5g dried leaves infused in 1 liter of hot water). After the treatment, 92% of patients had no detectable parasites in their bloodstream and there were significant improvements in subjective symptoms in 70% of the treated patients.
Commentary
One of the questions I am sometimes asked is whether the traditional galenical fluid extract of Artemisia annua can be used to provide clinically significant doses of artemisinin. The above pharmacokinetic study would support that this is the case. Interestingly, the pilot trial of the Artemisia annua tea preparation in malaria suggests that there could well be a synergistic advantage in using the tea or the galenical prepared from the whole herb, rather than the isolated compound artemisinin or its derivatives. The tea used in the pilot trial only delivered at best 10% of the normal therapeutic dose of artemisinin, but resulted in a substantial clinical effect.
These findings have particular relevance to the recently suggested use of Artemisia annua, or more specifically artemisinin, as an anticancer agent. This development is based on the finding that cancer cells have a much higher concentration of iron than normal cells. (It is thought that artemisinin interacts with iron to generate reactive oxygen species (free radicals) which kill the malaria parasite.) Tests on cancer cell lines have established that artemisinin is also selectively toxic to cancer cells, presumably because their higher iron levels result in cytotoxic effects following free radical generation after contact with artemisinin. (3-5)
References
1. Rath K, Taxis K, Walz G 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(2): 128-132
2. Miller M, Heide L. Malaria in Afrika: Wie hilfreich sind Arzneipflanzen? Z Phytother 2001; 22:77-81
3. Chen HH, Zhou HJ, Fang X. Inhibition of human cancer cell line growth and human umbilical vein endothelial cell angiogenesis by artemisinin derivatives in vitro. Pharmacol Res 2003; 48(3):231-236
4. Efferth T, Dunstan H, Sauerbrey A et al. The anti-malarial artesunate is also active against cancer. Int J Oncol 2001; 18(4):767-773
5. Woerdenbag HJ, Moskal TA, Pras N et al. Cytotoxicity of artemisinin-related endoperoxides to Ehrlich ascites tumor cells. J Nat Prod 1993; 56(6): 849-856
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