TOPIC:

Artemisia annua tea: prophylaxis against malaria
Pierre Lutgen
August 20, 2011

In recent years several NGO's, like IFBV, promote artemisia annua tea in tropical countries. This plant has excellent therapeutical properties against malaria, as demonstrated by several clinical trials. And as it is now growing in many African gardens and schools a lot of people have noticed that if they drink this tea regularly they are immune against malaria.
These prophylactic properties have been confirmed at large scale in Kenyan schools, partners of the IDAY network. In 2010 artemisia annua plantations were extended to some 50 schools. Pupils and teachers use the tea as cure against malaria (20 cups over 7 days), but once cured they continue taking one or two cups per week. And over the months they noticed that Artemisia annua has a strong prophylactic effect. Absenteeism for students and teachers dropped from 30 to almost 0 %. Much less money has to be spent for drugs and health care ; this money can now be used for educational needs. Dr T Arudo also reports that tea from this plant has a strong therapeutical effect on typhoïd fever and diarrhoea. A research team at Luxembourg had found in 2009 that Artemisia annua tea efficiently sterilizes water.
Recently a scientific paper confirmed the prophylactic effect against malaria on several hundred farmers in Uganda. (PE Ogwang et al., Brit J Pharm Res ISSN 2231-2919). A medical team at Luxembourg had already found in 2010 that Artemisia annua tea activates the lymphocytes in human blood, but only if the tea was poor in artemisinine. In Uganda it was found that A. annua extract devoid of artemisinin significantly boosts monocyte counts in albino rats (p<0.001).The action of flavonoids, polysaccharides and essential oils could explain the mechanism of prophylaxis of A. annua 'tea'.

Pierre Lutgen
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SOURCE:
www.mitosyfraudes.org/Pesti/prophylaxis.html



Artemisia annua prevents the transmission of malaria from man to mosquito

Pierre Lutgen
Luxembourg
June 25th , 2011

In the human body the parasite injected into the bloodstream by the mosquito undergoes the transformation from the asexual plasmodium into the sexual gametocytes which the mosquito is going to pick-up during its blood meal. The killing effect of artemisinin on gametocytes is known since twenty years and was first mentioned in in vitro trials at the John Hopkins University. These results were confirmed in 1993 by research teams in China and India and mentioned in the document WHO/MAL/ 98.1086. The Malaria Journal published a review article [1] in 2008 describing similar studies involving a few thousand people in several countries.
Taking regularly a cup of Artemisia annua tea could strongly reduce not only the plasmodium and but also the gametocyte load in the blood. We have received many anecdotic reports of this kind from African partners, but the effect deserves a well designed series of clinical trials in different human and geographical environment.
Several are planned in vitro and in vivo in cooperation with BELHERB (Association belgo-luxembourgeise pour la promotion des herbes médicinales). Children appear to constitute the majority of carriers of gametocytes as a study in Kenya showed [2]. It appears that the anopheles mosquito is preferably attracted by children and especially by those who are carriers of gametocytes. The efforts should thus concentrate on school children.
Other antimalarial drugs like chloroquine, amodiaquine, don't have this gametocytocidal effect. Pyrimethamine-sulfadoxine (SP) even increases the gametocyte density.
Artemisia annua tea taken over 7 days presents the advantage over ACT pills taken over 3 days because game-tocytes generally only develop after the 5th day of the infection.
Furthermore essential oils which are present in the tea like 1.8 cineol [3] and limonene [4] are known as antima-larials, they arrest parasite development at an early stage and inhibit thus the formation of gametocytes. Their presence in the blood could even have a preventive effect against malaria by strengthening the immune system.
The dream of malaria eradication could become true.
Pierre Lutgen
Luxembourg

Abstract of the data presented at the Conference on “Health and Education in Africa – Fighting malaria and dysentery” at the European Parliament in Brussels on June 16th 2011. The full text in French is available on request, This email address is being protected from spambots. You need JavaScript enabled to view it.

References:
LC Okell et al, Malaria Journal, 2008, 7(125)
LC Gouagna et al., East Afr Med Journ., 2003, 80 (12) 627-634
Vanessa Su et al., Flavour Fragr. J. 2008; 23: 315–318
IC Moura et al.,Antimicrobial Agents and Chemotherapy, September 2001, p. 2553-2558, Vol. 45, No. 9

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The essential role of sulfated polysaccharides in artemisia annua tea infusion
Pierre Lutgen
Luxembourg
October 31, 2011

So far the presence of polysaccharides in Artemisia annua has been barely covered in the scientific literature. The reason may be that they are only soluble in water and most of the Artemisia extracts for research are obtained by organic solvents. Polysaccharides are polymeric carbohydrates of high molecular weight. They have probably been overlooked in the research on Artemisia annua.

Their presence in other medicinal plants has been more extensively studied. They represent a very large part of the extracts. Neem contains 22 % of carbohydrates and moringa 5% and they are known to contri-bute to the therapeutical and immune stimulating properties of these plants (Lan Min-Bo et al., Food Science and Biotechn., 19, 2010, 1463-69). A recent article on Mongolian Artemisia rutifolia and Artemisia sphaerocephala find for water-soluble polysaccharides 6.4 % and 9.0 % respectively of the dry weight of the aerial parts of these plants (N Batbayar et al., Asian J Trad Medicines, 3, 2008). All safety and toxicity stu-dies suggest that polysaccharide products are well tolerated ( J Ramberg et al., Nutr J. 9, 2010 54). They have a proliferation effect on lymphocytes (X.Wei et al., Carbohydrate polymers 79, 2010, 418-422), con-tribute to the secretion of anti-inflammatory interleukins like Il-10 ( S Omarsdottir et al., Int Immunophar-macol. 6, 2006, 1642,-50), they stimulate the intestinal microbiota and reduce the pro-inflammatory cytokines like IL-8 in CaCo2 cells ( J Nutr 141, 2011, 971-977), activate macrophages, monocytes and splenic lymphocytes (SE Byson et al., Arch Pharm Res32, 2009, 1565-72).

Water soluble polysaccharides from artemisia iwayomogi suppress the apoptosis of thymocytes ( J Hwang et al., Biol Pharm. Bull., 208, 2005, 921-924). Those of Artemisia capillaris inhibit the adhesion of helicobacter pylori to host cells ( Woo Jeung et al., J Microbiol Biotechnol, 132003, 853-858). Those of Aloe vera are claimed to reduce inflammation and pain that is associated with psoriasis. Several artemisia species from Mongolia have wound healing properties which the authors relate to their polysaccharide content ( N Batba-yar et al., Asian J of Trad Med, 3, 2008, 33-40). Artemisia annua has been used for the treatment of lupus erythematosus ( YX Zhang et al., Immunopharmacol .Immunotoxicol 31, 2009. 625-30). Artemisia annua also contains 3.4 % of sulfur and the acidic polysaccharides it contains are probably sulfated.

Sulfated polysaccharides have excellent antioxidant activities ( M Rocha de Souza et al., J Appl Phycol 19, 2006, 153-160). They stimulate the immune system via glutathione. They are potent inhibitors of various viruses (M Baba et al., Antimicr Agents Chemother 32, 1988, 1742-45). The antiviral activity of marine sulfated polysaccharides is proportional to the degree of sulfatation. The activity is even abolished by desulfation. Sulfated polysaccharids act as anticoagulants and tumor inhibitors ( XZ WU et al., West Indian Medical Journal, 55, 2006). They have antagonistic effects on tumor cell migration and angiogenesis ( C Delma et al.,Cancer Prev Res 1, 2008 Suppl A4) . Sulfated polysaccharids from Azadirachta indica (neem) have a strong anti-herpetic activity. Some polysaccharides reduce liver damage and decrease high density cholesterol (Daye Cheng et al., Molecules, 16, 2011, 2542-50). They increase the level of glutathione in the body. Most of the polysaccharids in Artemisia tripartita are sulfated and inhibit ROS production ( G Xie et al., Phytochemistry, 69, 2008, 1359- 1371). Sulfated polysaccharides from Artemisia princeps accelerate the rate of thrombin inhibition (T Hayashi et al., Thrombosis Res. 87, 1997, 105-112) Artemisia plants contain a high concentration of 3-4 % of sulfur on dry weight. The concentration in other plants varies from 0.1 to 4.0 %.

In fact most of the Artemisia species are halophytic and in halophytic plant the concentration of sulfated polysaccharids is proportional to the salinity of the soil. Glyphophytes like rice, corn or beans don't contain sulfated polysaccharids ( RS Aquino et al., PlosOne 2011)

There are more polysaccharides in stems than in leaves and their solubility is also higher for this part of the plant due to a weaker binding to the lignin of the stems (YC Zhang. Life Science College of Ningxia Univer-sity)

The influence of polysaccharides on the solubility of hydrophobic molecules

Artemisinin and essential oils like limonene, eucalyptol, pinenes have a very low solubility in water. The latter are well described in the scientific literature for their bactericidal, antihelminthic, antiparasite and immune stimulating properties. Polysaccharides are amphiphilic, i.e. lipophilic and hydrophilic and they contribute to the dissolution of these compounds in water, forming stable emulsions with the solutes, with particle sizes around one micron. Polysacchrarides are water-swellable. This explains why most of them could be retained on filters with a 0.5 micron pore size and why they clog the filters in wine production. The polysaccharide content of polysaccharides in a plant can be estimated by the so called swelling test. A given quantity of dry material in agitated with water and left over night. The volume increase is then com-pared with the dry material.

The complexation by inclusion of artemisinin with cyclodextrins improves the oral bioavailability (J Wong et al., Int J Pharmaceutics, 227, 2001, 177-185). Polysaccharides form complexes with coenzymes ( R Bergeron et al., J Biol Chem. 250, 1975, 1223-30). This complexation and higher bioavailability may explain the much lower therapeutic doses against malaria required for artemisinin in tea infusions than for pure artemisinin. Polysaccharide droplets are well known as carriers for lipophilic drugs ( K Iwamoto et al., J Pharm Sci, 80, 1991, 219-24). Polysaccharides from Moringa olifeira are used as coating for paracetamol granules and retard the drug release (G. Kulkarni et al., Natural product radiance, May-June 2002). The solubility of highly branched sulphated acidic polysaccharides is enhanced in water containing sodium bicarbonate ( LC Vries-mann et al., Braz Arch Biol Technol 52, 2009).

The water soluble polysaccharides also dissolve the minerals like calcium, iron, manganese, aluminium barium, magnesium and contain 4-5 x more of these than in the dry plant material (G Shalamova et al. Plenum Publishing Corporation, 1985). The bioavailability of these complexed essential minerals is better than for the non chelated ions. But the chelation of iron by sulfated polysaccharids has the opposite effect. A high iron load in the bloodstream or an iron rich alimentation leads to a higher parasitemia. By removing the iron by chelation polysaccharids may have a beneficial effect against malaria infection (L Silva Costa et ., Mar Drugs 9, 2011, 952-966).This effect on parasitemia has been proven for other iron chelators (VR Gordeuk et al., Bloodjournal, 79, 1992, 308-312).

The bioavailabiliy of artemisinin is also enhanced in the tea. As Weathers states ( P. Weathers et al., Phytochem Rev, online 07 March 2010) : ”Of particular interest is the comparatively high level of transfer of artemisinin into the bloodstream from the plant material vs. the pure drug. There was 45 times more pure artemisinin fed to the mice than the amount fed via Artemisia annua leaves, yet almost the same amount appeared in the bloodstream. Furthermore, when equal amounts of pure drug ( 37 µg) and plant delivered drug were fed to each mouse, the amount of artemisinin found in the blood from the plant fed material far surpassed the level from pure delivered drug (undetectable).”.

According to study in Pakistan all Artemisia species contain small amounts of artemsinin (A Mannan et al., Malaria Journal, 9-310, 2010) which considering the Avogadro number leaves in any cup of Artemisia tea billions of artemisinin molecules for attacking each individual plasmodium in the bloodstream.

Their prophylactic role in malaria

Malaria is transmitted from mosquitoes to humans by sporozoites during the blood meal of the female anopheles. They travel to the liver where they invade hepatocytes and develop into merozoites which then invade red blood cells. The plasmodium sporozoites are coated with proteins (called circumsporozoite CS).These perform numerous functions for the parasite. They help the parasite to invade salivary glands in mosquitoes, they help the sporozoite to glide on solid surfaces (K. Matuschewski et al., The EMBO Journal, 21, 2002, 1597-62) and are involved in the attachment of sporozoites to liver cells. CS protein is one of the key targets recognized by the host immune system. But malaria sporozoites and the CS easily bind to sulfated glycoconjugates or polysaccharides ( SJ Pancake et al., Parasitologia, 35 1993, 77-80) inhibiting the invasion of hepatocytes and their infectivity. The sulfated polysaccharide fucoidan also has an appreciable effect inhibitory effect on amastigote multiplication in leishmanianiasis , but also imparts resistance to reinfection ( S Kar et al., J Antimicrob Chemother 66, 2011, 618-25). Trypanosoma cruzi amastigotes also have a glycoprotein coating which may be affected by the carbohydrates of Artemisia (S Kahn et al., Infection and Immunology, 64, 1996, 2649-2656). For antivirally active sulfated polysaccharides the in vivo efficacy mostly corresponds to their ability to inhibit the attachment of the virion to the host cell surface T Ghosh et al., Glycobiology 19, 2009, 2-15)

Sulfated polysaccharids also interfere with the plasmodium merozoite surface protein and inhibit the invasion of merozoites into erythrocytes in vitro and in vivo( JH Chen et al., Parasitology Research, 104, 245-250). At Heidelberg ( Y Adams et al., Antimicrob Agents Chemother. 50, 2006, 2850-82)it was confirmed that a large panel of sulfated saccharides displayed antimalarial inhibitory properties ( 50% inhibitory concentration of 7.4 µM). Heparin and other sulfated polysaccharides have been shown to inhibit blood-stage growth of plasmodium falciparum ( MJ Boyle et al., Bloodjournal, October 2011). Ginseng polysaccharides show preventive and curative antimalarial activities. This was confirmed in vivo inn malaria infected mice ( HH Chen et al., Pharm Biol. 49, 2011, 283-289). Ginseng polysaccharides show synergism with artesunate ( China Papers, January 16 2010). It is thus likely that the same synergism takes place in artemisia annua tea. US Patent 5512672 claims that sulfated polysaccharides combined with quinine show a strong inhibition of parasite infection.

By the same mechanism negatively charged glycoconjugates inhibit the cytoadherence of parasitized erythrocytes to the endothelium of capillaries ( Lihua Xiao et al., Infection and Immunity, April 1996, 1373-78). Mice infected with plasmodium berghei have reduced parasitemia after the administration of dextran sulfate, reduced anemia and an improved survival. It is thus possible that polysaccharides may reduce the severity of cerebral malaria.

Patent WO/2011/000032 extensively describes methods for designing and producing sulfated polysacchara-rides that have antiplasmodial activity, as well as methods for preventing and treating diseases including malaria with such molecules.

Frequent recurrent infections occur after artemisinin or artesunate motherapy, because the plasmodia treated by this strong peroxide enter in a stade of quiescence or encapsulated dormancy, where they are protected from the drugs lethal effects. They recover at a later date to resume normal growth ( A Codd et al., Malaria Journal 10, 2011, 56). Certain polysaccharides or peptidoglucans prevent excystement of dormant plasmodia.

Infected erythrocytes also adhere to the placenta (or more exactly to the chondroiton-4-sulfate CSA) and are linked to the severe disease outcome of pregnancy associated malaria. An Australian research group ( KT Andrews et al., Infect Immun 73, 2005, 4288-94)has screened 11 soluble sulfated polysaccharides, including cellulose sulfate (CS10), for their capacities to inhibit adhesion of infected erythrocytes on ex vivo placental tissue. Most of them inhibited this adhesion and particularly CS10 caused already bound infected erythrocytes to de-adhere in a dose dependant manner.

Pierre Lutgen
Luxembourg,
October 2011.

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