bk-2009-1021.ch012

Chapter 12

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Traditional Medicinal Plants and Malaria in Africa Mohammed Sayed Aly Mohammed Department of Cultivation and Production of Medicinal and Aromatic Plants, National Research Center, 33 El Tahrir St., Dokki, Cairo Egypt.

Malaria is considered one of the most prevalent diseases in Africa. Global infections are annually affecting 300-500 million people, with 90 percent of the cases in Sub-Saharan Africa. The incidence of infection has increased in recent times in many African countries despite ongoing programs seeking to reduce and alleviate the disease. Mortality associated with malaria is estimated as 1.5-2.7 million annually, and is rising as a result of increasing drug resistance. With global warming predicted to increase the emergence of malaria in many African countries and extend the regions where infections occur by expanding the ‘habitat of the insect vector’ additional national and international efforts are needed to address control strategies. In view of the problems that malaria infection is causing in Africa, this study sought to review the antimalarial properties of various medicinal plants, extracts and their components.

© 2009 American Chemical Society

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In African Natural Plant Products: New Discoveries and Challenges in Chemistry and Quality; Juliani, H., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2010.


218 In regions where malaria is endemic, adults experience 1-2 attacks annually, whereas children may suffer from 1-7 infections. Furthermore, about three million people (mostly in Africa) suffer from long-term neurological damage of malaria. Recent estimates of the global malaria burden have shown increasing levels of illness and death caused by malaria, reflecting the deterioration of the malaria situation in Africa rather than the improvement and reduction in cases as had been hoped. About 90% of all deaths from malaria occur in Africa, and the great majority of these are in children under the age of five (1-2). About 40% of the world's population is at risk of contracting malaria in 109 countries and territories around the world (2). While new programs seeking to develop effective immunizations and engineering microbes to produce antimalarials capture the worlds attention and funding for it represents exciting new science, the continued screening of natural plant products used today against malaria is being sourly overlooked. Traditional medicinal plants have been used for treating malaria and/or the symptoms of malaria for thousands of years, and remain a major source of the two main groups (artemisinin and quinine derivatives) of modern antimalarial pharmaceutical drugs. In developing countries, plants remain the main sources of medicine, and when the origin of modern drugs, it is the antimalarials that have largely come from plants or the chemistry of the synthetic antimalarials have been nature inspired. According to the World Health Organization, as many as 80% of the world's people rely for their primary health care on traditional medicine, most types of which use remedies made from plants (3). The use of traditional medicine in developing countries is increasing, in part because populations are increasing, because modern pharmaceutical drugs are often beyond the economic reach of a large part of the population, insufficient supply of some pharmaceutical drugs, the realization by some governments that want to encourage indigenous forms of medicine rather than rely on imported drugs, and strong moves to revive traditional cultures which include and rely on the traditional medicines (4-5). Traditional medicine or ethnomedicine is a set of empirical practices embedded in the knowledge of a social group often transmitted orally from generation to generation with the intent to solve health problems. It is an alternative to Western medicine and is strongly linked to religious beliefs and practices of indigenous cultures. Medicinal plants lore or herbal medicine is a major component of traditional medicine. The evidence for effectiveness of traditional medicinal plants in the treatment of infections is quite different from that, for example, of modern antibiotics. Traditional healers have for decades used many plants throughout African countries, to treat malaria, the symptoms of malaria as well as a wide range of deseases (5-6). Key among the factors contributing to increasing malaria mortality and morbidity is the widespread resistance of Plasmodium falciparum to conventional antimalarial drugs, such as chloroquine, sulfadoxinepyrimethamine and amodiaquine (7).


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Artemisia annua and Artemisinin (antimalarial) Artemisinin, the principal bioactive antimalarial compound and its derivatives from Artemisia annua, a Traditional Chinese Medicinal plant used against fevers and malaria, have yielded a potent new class of antimalarials. The anti-malarials derived from A. annua are considered an integral part of the solution where malaria has become resistant to other medicines and even in areas where resistance is not yet a problem (8). Artemisinin-based combination therapies (ACTs) have been recommended in the countries where falciparum malaria - the most resistant form of the disease- is endemic (9). While “ACTs for all” would be the ideal strategy, it is most impractical for poor and remote communities, politically unstable areas, and people who dislike the use of modern medicine (10). African scientists should be contributing to the improvement of A. annua L quality and to further develop artemisinin- based medicines, to help ensure a sustainable supply to meet market demand. While the world market for products containing artemisinin derivatives has grown rapidly, the available supply has been limited and not all artemisinin meets the required standards to produce the raw ingredients for pharmaceutical processing, making it all the more urgent to promote best practices in the cultivation, collection and processing of the raw material used to make the combination therapy. African scientists must advocate in the use and implementation of good agricultural and collection practices and growers and producers provide traceability and records for the African production of A. annua. Such records provide a detailed description of the cultivation and collection techniques and measures required for a harvest to meet quality requirements (11). However, the production of this crop requires a high degree of skills, excellent genetic materials, and the processing capabilities that also meet pharmaceutical requirements for the initial extraction of artemisinin from the harvested plant materials. Cultivation of A. annua requires a minimum of 6 months and extraction, processing and manufacturing of the final product require at least 2-5 months depending on the product formulation (12). High temperatures and moisture levels during post-harvest handling can damage the quality of the plant leading to a significant loss of artemisinin during the postharvest handling and storage period (13). It is in the processing and the next set of industrial steps in the purification and preparation of the artemisinin derivatives that are lacking in general in Africa. The objective of this study is to discuss the uses of African traditional plants to treat malaria in Africa, and to review the modern literature research on the bioactivities of these plants against the vector and the parasite (Plasmodium falciparum).


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Traditional Medicinal plants and Malaria There are numerous medicinal plants used in folkloric remedy of malaria, and the healers of African continent described these plants and their uses. Swartzia madagascariensis, Combretum glutinosum and Tinospora bakis are three plants of the folk medicine used by healers in Burkina Faso for the treatment of malaria (6). Cameroon healers used the boiling water extraction of stem bark and seeds of four medicinal plants, Entandrophragma angolens, Picaralima nitida, Schumanniophyton magnificum and Thomandersia hensii against malaria and report good results (14). Stem and leaves of Pothomorphe umbellata (Piperaceae), stem of Enantia polycarpa (Annonaceae) and the root of Trichilia emetica (Meliaceae) were used successfully in treating malaria in Cote D’ Lvoire (15). Meanwhile, traditional healers often use water decoctions and macerations of Emilia discifolia, Senecio stuhlmannii, Indigofera emarginella and Aspilia africana, traditional medicinal plants of East and Central Africa for malaria remedy (16). Ethiopian medicinal plants, Dingetegna (Taverniera abyssinica) and Endod (Phytolacca dodecaandra) are used for malaria disease (17), In Ghana, dried root decoctions of Cryptolepis sanguinolenta, prepared by boiling the powdered roots in water, are used in traditional medicine to treat various forms of fevers, including malaria (18). Some of the anti-malarial species for example, Warburgia ugandensis are already known to be over-exploited and in some parts of Kenya now rare (19). In Madagascar, a decoction of Cinnamosma fragrans (Canellaceae) leaf and bark is drunk (1 bowl, 3–4 times daily) to relieve malarial symptoms, while a decoction of the leaf and bark of Desmodium mauritianum (Leguminosae), is mixed with a selection of five plants from (Ficus megapoda, Nymphaea lotus, Noronhia linocerioides, Vepris ampody, Zanthoxylum madagascariense, Gambeya boiviniana, Peddia involucrata). This decoction is drunk (1 bowl, 3–4 times daily) to relieve malarial symptoms (20) (Table I). While specific plants have been used against malaria, herbalists and healers have long recognized that not all plant tissues are equally effective, and thus they recommend and use different plant tissues dependent upon the species. Opilia celtidifolia (Opiliaceae) and Trichilia emetica (Meliaceae) are well known to the traditional healers of Mali for their use against malaria. The leaves are the most frequently used plant part (56.3%), the root and fruits are used about 30% and 8.5% respectively, and the less used plant part is the bark (5.3%) (21). Malaria was reported to be the most common condition treated by traditional healers in Uganda. These healers used plants as their most important source of natural products for malaria treatment. Plant extracts of Maesa lanceolata, Conyza sp., Rhus natalensis, Toddalia asiatica, Bothriocline longipes and Trimeria bakeri, showed high activity against the blood stage of P. falciparum (22).


221 Table I. Traditional medicinal plants (leaf and bark) preparations and doses used against malaria in Madagascar.


Scientific name Cinnamosma fragrans Desmoium mauritianum Dracaena reflexa L. Ficus megapoda Nymphaea lotus L. Peddiea involucrata Tristellateia madagascariensis Vepris ampody Zanthoxylum tsihanimposa

Family Canellaceae Fabaceae Agavaceae Moraceae Nymphaeaceae Thymelaeceae Malpighiaceae Rutaceae Rutaceae

Doses 1 bowl, 3-4 times daily 1 bowl, 3-4 times daily 1 bowl, 3-4 times daily 1 bowl, 3-4 times daily 1 bowl, 3-4 times daily 1 bowl, 3-4 times daily 2-3 glasses daily 1 bowl, 3-4 times daily 1 bowl, 3-4 times daily

NOTE: All preparations are decoctions from leaf and bark. SOURCE: Modified from Randrianarivelojosi et al. 2003 (20).

In the French Guiana, many medicinal plants are used as traditional antimalarial remedies. Of the different 23 species that were tested, Irlbachia alata, Picrolema pseudocoffea, Quassia amara, Tinospora crispa and the multi components recipe showed showed high in vitro activity against P. falciparum (23) (Table II). Bioactive Compounds of Medicinal Plants and Malaria The antiplasmodial activity of five akaloids (γ - fagarine, Nbenzoyltryamine, skimmianine, dictamnine and 4-methoxy-1 methyl-2(1H)quinoline), extracted by decoction from Zanthoxylum tsihanimposa stem bark were tested upon P. falciparum. The quinoline alkaloid γ-fagarine was the most potent of five alkaloids, being found to be 3.4 times more active than dictamnine and 1.4 times more active than skimmianine. The presence of the methoxy group in positions C4 and C8 appears to be important for bioactivity (20). Argemone subfusiformis dried leaves, flowers and seeds were extracted with ethanol-water (70-30%) for 48 h, the aqueous-solution obtained was evaporated under vacuum and the resdue was directly assayed. The antiplasmodial activity was good (24), and extracts were rich in isoquinolleinic alkaloids. In above ground parts, protopine, berberine and allocryptopine were identified (27). According to Sriwilaijaron et al. (28) berberine prevents the development of Plasmodium falciparum by inhibition of its telomerase activity. Aspidospermine one indole alkaloid was isolated from bark of Aspidosperma quebracho-blanco, displaying antimalarial activity on Plasmodium falciparum (29).


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Table II. Mode of preparation of selected antimalarial remedies. Species Geissospermu m laevis Irlbachia alata

Familiy Apocyna ceae Gentiana ceae

Part Bark

Picrolemma pseudocoffea Pseudoxandra cuspidate Pterocarpus rohrii

Simarou baceae Annonac eae fabaceae

Leaves

Quassia amara L.

Simarou baceae

Leaves and stem

Tinospora crispa L. Zanthoxylum rhoifolium

Menisper maceae Rutaceae

Stem

Multi ingredient recipe

Leaves and roots

Bark Leaves and bark

Bark

Preparation of recipe 40 g in 1l water, boiled for 15 min. 150 g fresh leaves are boiled in 300 ml water for 10 min.150 g roots are boiled in 200 ml water fore 10 min. 20 g are boiled in 1l water for 10 min. 200 g of inner bark, boil for 15 min in 500 ml water. 15 g fresh leaves are boiled in 1500 ml water for 10 min., 15x 10 cm bark piece, boil for 15 min in 800 ml water. 20 g entire fresh leaves,boil for 10 min in 1l water, 100 g stem (cut pieces) are boiled in water for 15 min. 15 cm is cut in small pieces, boil for 15 min in 500 ml water 400 g of inner bark are boiled in 1500 ml water until liquid reduces by half. P. pseudocoffea, 20 g fresh leaves, Q. amara, 8 g fresh leaves, G. laevis bark, 40 g bark boiled in 1500 ml water/15 min

SOURCE: Partial data from Bertani et al., 2005 (23).

Ethanolic leaves extract of Castela texana was evaluated, and antimalarrial activity was reported for five quassinoids, with level of activity ranking from 0.01 μg/ml to 0.92 μg/ml (28). If the activity observed in the ferriprotoporphyrin biomineralization inhibition test (FBIT) of this extract is due to quassinoids-like molecules, the same mechanism of action could be suggested, as structure/activity relationship studies of quassinoids have shown than the oxymethylene bridge is necessary for antimalarial activity (29). The bark of Vallesia glabra stem has been shown to contain indole alkaloids such as apparicine, aspidospermatine, condylocarpine, haplocidine, tubotawine, vincadifformine (30). As these types of alkaloids are known to posses antimalarial activity, it is not surprising to have found such promising in vitro activity very much alike the one of Aspidosperma quebracho-blanco bark. Methanolic and methylene chloride extracts of the leaves of Hymenocardia acida were found active against P. falciparum (31). Tannins and the alkaloid hymenocardine have been identified in the leaf extracts of H. acida (32). From



223 investigations of in vitro antimalarial screening of medicinal herbal extracts, the n-butanolic extract from the root of Wikstroemia indica showed a potent inhibitory effect. Fractionation of the active extract led to the isolation of two biflavonoids, sikokianin B and sikokianin C with IC50 values 0.54 μg/mL and 0.56 μg/mL, respectively, against the chloroquine-resistant strain of Plasmodium falciparum (33). Phytochemical investigation of the 80% ethanolic extract of stem bark of Vismia orientalis Engl. (Clusiaceae), a plant used in traditional medicine in Tanzania, resulted in the isolation and spectroscopic characterization of 3-geranyloxy-6-methyl-1,8-dihydroxyanthraquinone, emodin, vismione D and bianthrone A1. Vismione D exhibited a broad range of antiprotozoal activities against Trypanosoma brucei rhodesiense and T. cruzi (IC50 < 10 μg/mL), Leishmania donovani (IC50 0.37 μg/mL) and Plasmodium falciparum strain K1 (IC50 1.0 μg/mL). However, it was also slightly cytotoxic against human L6 cells (IC50 4.1 μg/mL). Emodin showed antileishmanial activity (IC50 2.0 μg/mL), while its IC50 against L6 cells was 20.3 μg/mL. Other antiprotozoal activities observed for emodin against both Trypanosoma species and P. falciparum, for bianthrone A1 against T. b. rhodesiense and P. falciparum, and for 3-geranyloxy-6-methyl-1,8-dihydroxyanthraquinone against T. b. rhodesiense, L. donovani and P. falciparum were in the range of 10 to 50 μg/mL. (34). In the search for new plant-derived biologically active compounds against malarial parasites, five essential oils extracted from the Cameroonian plants Xylopia aethiopica, Xylopia phloiodora, Pachypodanthium confine, Antidesma laciniatum, and Hexalobus crispiflorus were evaluated in regard to their antiplasmodial activity against the W2 strain of Plasmodium falciparum. The oils were obtained from the plants with 0.12, 0.13, 0.18, 0.6 and 0.1% yields (relatively to dried material weight) respectively. Analysis by gas chromatography and mass spectrometry identified mainly terpenoids, among which α-copaene, γ-cadinene, δ-cadinene, α-cadinol, spathulenol and caryophyllene oxide were most commonly found The five oils were active against Plasmodium falciparum in culture. The most effective was the oil of Hexalobus crispiflorus, with an IC50 of 2 μg/ml. (35). The Amazon Indians Waiãpi living in the West of Amapá State of Brazil, treat malaria with an inhalation of vapor obtained from leaves of Viola surinamensis. The antimalarial activity of the aromatic volatile plant extracts from leaves, showed that nerolidol (an acyclic oxygenated sesquiterpene) was identified as one of the active principles (36). Another recent study suggested the presence of an active isoprenoid pathway for biosynthesis of isoprenic chains of coenzyme Q in P. falciparum (37), parasites treated with nerolidol showed decreased ability to synthesize coenzyme Q in all intraerythrocytic stages. A challenge would be to now identify which African medicinal plants contain similar chemistry. Traditional Plants that Repel Mosquitoes Mosquitoes are important vectors of many diseases, particularly malaria, as well as being nuisance pests. Repellents minimize human contact with



224 mosquitoes. Repellents and insecticides have long been recognized as an important strategy in the control of malaria. Repellents based on essential oils are being developed as an alternative to synthetic components such as DEET (N,N-diethyl-m-ethylbenzamide). The effect of essential oils is varied depending on geographic origin of the plants and the oil chemistry. Many essential ols has been studied for their mosquito repellant activitiy. The essential oils from Pogostemon cablin, Syzygium aromaticum and Zanthoxylum limonella plants performed as mosquito repellents about as equally well as citronella oil. (38). In addition, essential oils extracted from multiple species of Tagetes, such as T. patula, T. erecta, and T. minuta, have shown nematicidal, fungicidal and insecticidal activity (39), extracts of T. minuta, whose main component was β-ocimene (62.8%), were toxic against mosquitoes (40). The main components of Minthostachy mollis essential oil repellent against mosquitoes were pulegone (52.6%), menthone (35.8%) and limonene (10.1%) (40). The essential oil from Rosmarinus officinalis was effective in terms of repellence time against mosquitoes (41). The main components of essential oil for R. officinalis include camphor (34%), verbenone (25%) and (E)caryophyllene (15%). Camphor also found in Baccharis spartioides (50.5%), may be responsible for repellence of these plants (42). Some Eucalyptus species have been evaluated for their potential as mosquitoes repellents, principally Corymbia citriodora Hook (also known as Eucalyptus maculate citriodora) (43), the repellent properties of E. saligna may be attributed to 1,8-cineole, as this compound accounted for 93.2% of the total extracted essential oil. This essential oil was also the only one to significantly decrease in terms of repellence time at concentrations below 90%. A study using 1,8-cineole showed moderate effects as a feeding and ovipostion deterrent of mosquitoes (44). cis-Carveol is one of constituents in the essential oils of six plants growing in Kenya which were screened for repellent activities against Anopheles gambiae sensu stricto. The oils of Conyza newii (Asteraceae) and Plectranthus marrubioides (Lamiaceae) were the most repellent (45). Repellence tests with essential oils at 90% concentration indicated that five essential oils were effective repelling mosquitoes for 90 min (Table III). The essential oil of Acantholippia seriphioides was repellent even at the lowest concentration tested (12.5%). Repellence by this essential oil was expected because its main components are p-cymene (53%) and thymol (47%), both components showed repellent activity for approximately 1h against mosquitoes species (46). At concentrations of 12.5%, Aloysia citriodora, Baccharis spartioides and Rosmarinus officinalis showed the longest repellency times. Comparisons of the principal components of each essential oil suggest that limonene and camphor were the main components responsible for the repellent effects (46).


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Table III. Essential oils that repell mosquitoes listed in order of repellency time (46). Essential oil (concentration at 90%) Achyrocline satureioides Hyptis mutabilis Anemia tomentosa Acantholippia seriphioides Baccharis spartioides Eucalyptus saligna Minthostachy mollis Rosmarinus officinalis Tagetes minuta SOURCE: Partial data presented (46).

Repellence time 3.3 + 3 20.0 +10 60.0 +30 60.0 + 30 90.0 + 0 90.0 + 0 90.0 + 0 90.0 + 0 90.0 + 0

The components of the essential oil extracts from Callicarpa americana and Callicarpa japonica, containing callicarpenal, intermedeol, and spathulenol proved to be highly effective biting deterrents against Anopheles stephensi and Aedes aegypti. These compounds and other terpenoids may represent useful alternatives to conventional, so-called synthetic insect repellents currently on the market. (47). In laboratory tests, ethyl acetate extracts of Hyptis suaveolens from GuineaBissau and Rhododendon tomentosum, H. Harmaja, and Myrica gale signiÞcantly reduced probing activity of Aedes aegypti. The essential oils of these species were dominated by terpenes hydrocarbons, (H. suaveoles, βcaryphyllene, R. tomentosum, p-cymene, M. gale, myrcene, phellandrene and αpinene) (48). While, nepetalactone, the essential oil of catnip (Nepeta cataria) that gives the plant its characteristic aroma, has been reported to be about ten times more effective at repelling mosquitoes than DEET (49).

Traditional Medicinal Plants and Clinical Trials There are and have been clinical trials conducted in Africa with medicinal plants for the treatment of malaria. For example, the aqueous root extract of Cryptolepis sanguinolenta shows promise in the treatment of falciparum malaria. Parasite clearance was only one day longer with this remedy than with chloroquine, and the clearance of fever was faster by 12 hours (50). In another trial, comparing the treatment of falicparum malaria with quinine or with infusions of Artemsia annua, the infusions resulted in good parasite clearance at day 7 (51). Promising trypanocidal activity with IC50 values below 10 μg/ml was found in 32 extracts of 13 plant species. The most active extracts with IC50 values below 1 μg/ml were derived from Annona senegalensis, Bussea occidentalis and Physalis angulata (52). Extracts from the plants Emilia discifolia, Senecio stuhlmannii, Indigofera emarginella and Aspilia africana were reported to possess antiplasmodial



226 activity. Aspilia. africana exhibited the highest antiplasmodial activity against both the chloroquine-sensitive, and chloroquine-resistant strains of P. falciparum (16). Aqueous, methanol, hydromethanol extracts from the roots bark of Swartzia madagascariensis, methanol and hydromethanol extracts from the leaves of Combretum glutinosum and aqueous and alkaloidal extracts from the roots of Tinospora bakis were also screened against Plasmodium falciparum chloroquine-resistant strain W2 in vitro. Results of these screens showed that the methanol and hydromethanol extracts of Swartzia madagascariensis, hydromethanol extracts of Combretum glutinosum and alkaloidal extracts of Tinospora bakis were active (5 µg/ml < IC50 < 50 µg/ml) (6). Other compounds with antiplasmodial activity derived from Senecio selloi and Eupatorium rufescens plants were also found to be active (53). Fifteen crude extracts from the stem bark and seeds of four medicinal plants, Entandrophragma angolense, Picralima nitida, Schumanniophyton magnificum and Thomandersia hensii were tested in vitro for their antimalarial activity against the chloroquine-resistant Plasmodium falciparum W2 strain. The results showed that the extracts of these plants possessed some antimalarial activity, with the methanol extract of Picralima nitida demonstrating the highest activity in vitro (14). A slight in vivo antiplasmodial activity of the aqueous extract of Erythrina senegalensis was observed when tested against Plasmodium berghei (54), while the ethanolic stem bark extract showed a good activity against Plasmodium falciparum, confirming s the antiparasitic potential of this plant (15). Ten ethanolic (EtOH) and ten dichloromethanic (CH2Cl2) extracts from different parts of nine African medicinal plants used in Congolese traditional medicine for the treatment of malaria, were submitted to a pharmacological test to evaluate their effect on P. falciparum grown in vitro. Of these plant species, 14 (70%) extracts including EtOH and CH2Cl2 from Cassia occidentalis leaves, Cryptolepis sanguinolenta root bark, Euphorbia hirta whole plant, Garcinia kola stem bark and seeds, Morinda lucida leaves and Phyllanthus niruri whole plant produced more than 60% inhibition of the parasite growth in vitro (at 6 μg/ml). Extracts from E. hirta, C. sanguinolenta and M. morindoides also showed a significant chemosuppression of parasitaemia in mice infected with P. berghei at orally given doses of 100-400 mg/kg per day (55).


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Conclusions Medicinal plants can offer alternative remedies with tremendous opportunities compared to synthetic modern pharmaceuticals. They not only provide access and affordable medicine to poor people; they can also generate income, employment and foreign exchange for developing countries. Many traditional healing herbs and plant parts have been shown to have medicinal value, especially in the rural areas and these can be used to prevent, alleviate or cure several human diseases. The safety of raw medicinal plant materials clearly provides a compelling rational for both additional scientific study and national health care policies that can address the judicious use of traditional medicines to improve the quality and quantity of these materials and to ensure their efficacy. This review has shown that many plants from Africa and other continents have been reported to be used to treat malaria in traditional medicine. Modern in vitro screens against the P. falciparum has confirmed the antimalarial properties for many of these plants and their extracts and clearly given the magnitude of the problem and the national costs due to malaria illness, death and suffering, the use of medicinal plants either in traditional manners and/or as leads for new compounds that may serve in the future for new anti-malarial drugs presents scientific opportunities. The mosquito repellent properties of essential oils extracted from aromatic plants, also show promising results in the fight against malaria infection by reducing mosquito bites.. Traditional medicines could be an important and sustainable source of anti-malarial agents. Given the increasing reports of drug resistance and difficulties in poor areas of being able to afford and access effective anti-malarial drugs, the search for additional strategies continues and in this medicinal plants can and should play an increasingly important role. Clinical trials are needed to incorporate this traditional knowledge in current medical practices and though such trials are always considered costly, the preselection of the most promising herbal or plant based treatments from in vitro studies into finely crafted modern clinical trials needs to be considered against the costs that will be incurred by those that would otherwise be infected with malaria.

References 1. 2. 3. 4. 5.

Butler, D. Nature 1997, 386, 535-536. Roll Back Malaria Partnership. Global Malaria Action Plan. World Health Organization, 2008, Geneva, Switzerland. Murray, CJL.; Lopez, AD. Global health statistics. Harvard: WHO, 1996. Brinkmann, U.; Brinkmann, A. Trop Med. Parasitol. 1991, 42, 204-213. Trape, JF.; Pison, G.; Preziosi, MP.; et al. C R Acad Sci Paris, Sciences de la Vie 1998, 321, 689-697.


228 6. 7. 8.


9.

10.

11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24.

Ouattara, Y.; Sanon, S.; Traoré, Y.; Mahiou, V.; Azas, N.; Sawadogo, L. African Journal of Traditional, Complementary and Alternative Medicines 2006, 3, 75-81 Golenser, J.; Waknine, J.H.; Krugliak, M.; Hunt, N.H.; Grau, G.E. Current perspectives on the mechanism of action of artemisinins. International Journal of Parasitology 2006, 36, 1427–1441. de Riddera, S.; van der Kooy, F.; Verpoorte, R. Artemisia annua as a selfreliant treatment for malaria in developing countries. J. Ethnopharmacol. 2008, 120, 302-314. Rational Pharmaceutical Management Plus Program. 2005. Changing Malaria Treatment Policy to Artemisinin-Based Combinations: An Implementation Guide. Submitted to the U.S. Agency for International Development by the RPM Plus Program. 2005, Arlington, VA, USA. Willcox, M.; Falquet, J.; Ferreira, J.F.S.; Gilbert, B; Hsu, E.; de Magalhèes, P.M.; Plaizier-Vercammen, J.; Sharma, V.P.; Wright, C.W.; Yaode, W. African Journal of Traditional, Complementary and Alternative Medicines, 2007, 4(1), 121-123. World Health Organization. WHO. Monograph on good agricultural and collection practices (GACP) for medicinal plants. WHO, 2003, Geneva, Switzerland. Ferreira, J.F.S.; Simon, J.E.; Janick, J. Horticultural Reviews. 1997, 19, 319-371. World Health Organization. WHO. Monograph on good agricultural and collection practices (GACP) for Artemisia annua L. WHO, 2006, Geneva, Switzerland. Bickii, J.; Tchouya, GRF.; Tchouankeu, JC.; Tsmo, E. African Journal of Traditional, Complementary and Alternative Medicines 2007, 4, 107-111. Atindehou K.; Schmid, C.; Burn, R.; Kone, M. W.; Traore, D. J. Ethnopharmacol. 2004, 90, 221-227. Waako,P.J.; Katuura,E.; Smith,P.; Folb,P. African Journal of Ecology 2007, 45, 102-106. Fullas, F. Ethiopian Traditional Medicine: Common Medicinal Plants in Perspective. Sioux City, IA (USA). Boye GL, Ampofo O. Medicinal Plants in Ghana. In: Economic and Medicinal Plants Research Vol. 4 Wagner and Farnsworth NR, (Ed).. Plants and Traditional Medicine. London: Academic Press; 1990. p 32-3. Beentje H: Kenya Trees, Shrubs and Lianas. NMK Nairobi; 1994. Milijaona, R.; Valérie, T. R.; Harison, R.; Peter, K. C.; Michel, R.; Dulcie, A. M.; Philippe,M. Malaria Journal 2003, 2, 25. Adiaratou, T.; Drissa, D. S.D.; Hilde,B.; Berit,S.P. Journal of Ethnobiology and Ethnomedicine 2005, 1, 7. Katuura, E.; Waako,P.; Ogwal-Okeng, J.; Bukenya-Ziraba, R. African Journal of Ecology 2007, 45, 48–51. Bertani, S.; Bourdy, G.; Landau, I.; Robinson, J. C.; Esterre,Ph.; Deharo, E. Evaluation of French Giana Traditional antimalarial remedies. Journal of Ethnopharmacology 2005, 98, 45-54. Bourdy, G.; Oporto P.; Gimenez A. ; Deharo E. J Ethnopharmacol. 2004, 93(2-3), 269-77.



229 25. Bandoni, A. L.; Mendiondo, M. E.; Rondina, R. V.; Coussio, J. D. Lloydia. 1972, 35, 69-80. 26. Sriwilaijaron, N.; Petimtr, S.; Mutirangurac, A.; Ponglikitmongkola, M.; Wilairata, P. Parasitol Int.. 2002, 51(1), 99-103. 27. Mitaine-Offer, A.C.; Sauvain, M.; Valentin, A.; Callapa, J.; Mallié, M.; Zèches-Hanrot, M.; Phytomedicine, 2002, 2, 142–145. 28. Dou, J.; McChesney, J. D.; Sindelar, R. D.; Goins, D. K.; Walker, L. A. Journal of Natural Products. 1996, 59, 73-76. 29. Fukamiya, M. O.; Lee, K. H. In: Rahman,A., Elsevier Science Publishers, Amsterdam,1990, 7, 369-404. 30. Zeches, M.; Mesbah, K.; Richard, B.; Moretti, C.; Nuzillard, J. M.; Le MenOlver, L. Planta Medica. 1995, 61(1), 89-91. 31. Vonthron-Senecheau, C.; Weniger, B.; Quattara, M.; Bi, F. T.; Kamenan, A.; Lobstein, A.; Brun, R.; Anton, R. Journal of Ethnopharmacology. 2003, 87, 221-225. 32. Kerharo, J.; Adam, J. G. La Pharmacopee Senegalaise Traditionnelle: Plantes Medicinales et Toxiques. Vigot Freres, Paris, 1974. 33. Nunome, S.; Ishiyama, A.; Kobayashi, M.; Otoguro, K.; Kiyohara, H.; Yamada, H.; Omura, S. Planta Med., 2004, 70, 76-78. 34. Mbwambo, Z.H.; Apers, S.; Moshi, M.J.; Kapingu, M.C.; Van Miert, S.; Claeys, M.; Brun, R.; Cos, P.; Pieters, L.; Vlietinck, A. Planta Med., 2004, 70, 706-710. 35. Boyom, F.F.; Ngouana, V.; Zollo, P.H.; Menut, C.; Bessiere, J.M.; Gut, J.; Rosenthal, P.J. Phytochem., 2003, 64(7), 1269-1275. 36. Lopes, N.P.; Kato, M.J.; Andrade, E.H.A.;. Maia, J.G.S; Yoshida, M.; Planchart, A.R.; Katzin, A.M. J. Ethnopharm. 1999, 67, 313-319. 37. de Macedo, C.S.; Uhrig, M.L.; Kimura, E.A.; Katzin, A.M. FEMS Microbiol Lett. 2002, 207(1), 13-20. 38. Trongtokit, Y.; Rongsriyam, Y.; Komalamisra, N.; Apiwathnasorn, C. Phytother Res. 2005, 19(4), 303-9. 39. Vasudevan, P.; S.Kashyap; S.Sharma. Biores. Technol. 1997, 62, 29-35. 40. Ruffinengo, S. ; Eguaras, M. ; Floris, I. ; Faverin, C. ; Bailac, P. ; Ponzi, M. ; J. Econ Entomol., 2005, 98(3), 651-5. 41. Choi, W.S. ; Park, B.S. ; Ku, S.K. ; Lee, S.E. J. Am Mosq Control Assoc. 2002, 18(4), 348-351. 42. Spurr, E. B.; P. G. McGregor. Science for Conservation 232, Department of Coservation, Wellington . 2003. 43. Seyoum, A. ; Pålsson, K. ; Kung'a, S. ; Kabiru, E.W. ; Lwande, W. ; Killeen, G.F. ; Hassanali, A. ; Knols, B.G. Trans. R. Soc. Trop. Med. Hyg. 2002, 96(3), 225-31. 44. Watanabe, K.; Shono, Y.; Kakimizu, A.; Okada, A.; Matsuo, N.; Satoh, A.; Nishimura, H.. J. Agric. Food. Chem. 1993, 41, 2164-2166. 45. Omolo, M.O.; Okinyo, D.; Ndiege, I.O.; Lwande, W.; Hassanali, A.. Phytochem. 2004, 65, 2797-2802. 46. Gillij, Y.G., Gleiser, R.M. ; Zygadlo, J.A. Bioresour. Technol. 2008; 99(7), 2507-15 47. Cantrell, C.I.; Klun, J.A.; Bryson, C.T.; Kobaisy, M.; Duke S.O. J. Agric. Food. Chem. 2005, 53, 5948-5953.



230 48. Jaenson, T.G. ; Pålsson, K. ; Borg-Karlson, A.K. J. Med. Entomol. 2006, 43(1), 113-9. 49. Webb, C.E. ; Russell, R.C. J. Am. Mosq. Control. Assoc. 2007, 23(3),3514. 50. Boye, G.L. Proceeding of an International Symposium on East-West Medicine, Seoul, Korea, 1989, 75-77. 51. Mueller, M.S.; Runyambo, N.; Wagner, I.; Borrmann, S.; Dietz, K.; Heide, L. Trans. R. Soc, Trop, Med, Hygeine 2004, 98, 318-21. 52. Freiburghaus, F.; Kaminsky, R. ; Nkunya, M.H.H.; Burn, R. J. Ethnopharmacol. 1996, 55, 1-11. 53. Ruecker, G.; Schenkel, E.P.; Manns, D.; PlMayer, R. Planta Med. 1996, 62, 565-566. 54. Saidu, K.; Onah, J.; Olusola, A.; Wambebe, C.; Gamaniel, K. J. Ethnopharmacol. 2000, 71 , 275–280. 55. Tona, L. : Ngimbi, N.P. ; Tsakala, M. ; Mesia, K. ; Cimanga, K. ; Apers, S. ; De Bruyne, T. ; Pieters, L. ; Totté, J. ; Vlietinck, A.J. J Ethnopharmacol. 1999, 68(1-3), 193-203.


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