Review
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World J Pharmacol. Dec 9, 2014; 3(4): 39-55
Published online Dec 9, 2014. doi: 10.5497/wjp.v3.i4.39
Dried-leaf Artemisia annua: A practical malaria therapeutic for developing countries?
Pamela J Weathers, Melissa Towler, Ahmed Hassanali, Pierre Lutgen, Patrick Ogwang Engeu
Pamela J Weathers, Melissa Towler, Department of Biology and Biotechnology, Worcester Polytechnic Institute, Worcester, MA 01609, United States
Ahmed Hassanali, School of Pure and Applied Sciences, Kenyatta University, Nairobi 20100, Kenya
Pierre Lutgen, IFBV-BELHERB, PO Box 98, L-6908 Niederanven, Luxembourg
Patrick Ogwang Engeu, Natural Chemotherapeutics Research Institute, Ministry of Health, PO Box 4864 Kampala, Uganda
Author contributions: Weathers PJ, Towler M, Hassanali A, Lutgen P and Engeu PO all participated in writing the article; Hassanali A, Lutgen P and Engeu PO provided clinical data; Weathers PJ and Towler M conducted analyses of lab and field samples.
Supported by Worcester Polytechnic Institute and University of Massachusetts Center for Clinical and Translational Science partially; partially by Award Number NIH-R15AT008277-01 from the National Center for Complementary and Alternative Medicine
Correspondence to: Pamela J Weathers, Professor, Department of Biology and Biotechnology, Worcester Polytechnic Institute, 100 Institute Rd., Worcester, MA 01609, United States. weathers@wpi.edu
Telephone: +1-508-8315196 Fax: +1-508-8315936
Received: June 25, 2014
Revised: September 9, 2014
Accepted: October 1, 2014
Published online: December 9, 2014
Processing time: 169 Days and 7.7 Hours
Abstract

Artemisinin from the plant Artemisia annua (A. annua) L., and used as artemisinin combination therapy (ACT), is the current best therapeutic for treating malaria, a disease that hits children and adults especially in developing countries. Traditionally, A. annua was used by the Chinese as a tea to treat “fever”. More recently, investigators have shown that tea infusions and oral consumption of the dried leaves of the plant have prophylactic and therapeutic efficacy. The presence of a complex matrix of chemicals within the leaves seems to enhance both the bioavailability and efficacy of artemisinin. Although about 1000-fold less potent than artemisinin in their antiplasmodial activity, these plant chemicals are mainly small molecules that include other artemisinic compounds, terpenes (mainly mono and sesqui), flavonoids, and polyphenolic acids. In addition, polysaccharide constituents of A. annua may enhance bioavailability of artemisinin. Rodent pharmacokinetics showed longer T½ and Tmax and greater Cmax and AUC in Plasmodium chabaudi-infected mice treated with A. annua dried leaves than in healthy mice. Pharmacokinetics of deoxyartemisinin, a liver metabolite of artemisinin, was more inhibited in infected than in healthy mice. In healthy mice, artemisinin serum levels were > 40-fold greater in dried leaf fed mice than those fed with pure artemisinin. Human trial data showed that when delivered as dried leaves, 40-fold less artemisinin was required to obtain a therapeutic response compared to pure artemisinin. ACTs are still unaffordable for many malaria patients, and cost estimates for A. annua dried leaf tablet production are orders of magnitude less than for ACT, despite improvements in the production capacity. Considering that for > 2000 years this plant was used in traditional Chinese medicine for treatment of fever with no apparent appearance of artemisinin drug resistance, the evidence argues for inclusion of affordable A. annua dried leaf tablets into the arsenal of drugs to combat malaria and other artemisinin-susceptible diseases.

Keywords: Malaria; Infectious disease; Artemisia annua; Artemisinin; Combination therapy; Artemisinin combination therapy

Core tip: Artemisinin, extracted from the plant Artemisia annua (A. annua) L., and artemisinin derivatives are the current best antimalarial therapeutics and are delivered as artemisinin combination therapy (ACT). Availability and cost are problematic for the developing world where malaria is endemic. Oral consumption of A. annua dried leaves is more effective than the pure drug. A tea infusion of the leaves has prophylactic effects. Cost of producing and delivering the tea and A. annua dried leaf tablets is much more affordable than ACT.