17septembre

Artemisia is prophylactic against malaria

ARTAVOL

ARTAVOL from Uganda PGs are important soluble mediators involved in the immune response to invading pathogens and this may explain the strong prophylactic effect of ARTAVOL, a drug developed by Dr Patrick Ogwang from the University of Makerere and the Ministry of Health in Uganda. The powder contains lemongrass (Cymbopogon citratus), avocado (Persea americana) and Artemisia annua. Avocados contain 9% of fatty acids and 71 % of these are monounsaturated. The fatty acid of lemongrass is very rich in linoleic and oleic acid. Linoleic acid generates a strong PGE₂ production and oleic acid a weaker one. The prophylactic effect of lemongrass and neem is known and well described. M Farahna, S Bedri, S Khalid, Mustafa Idris, C. Pillai, and E A. Khalil Anti-plasmodial effects of Azadirachta indica in experimental cerebral malaria: Apoptosis of cerebellar Purkinje cells of mice as a marker. N Am J Med Sci. 2010 Nov; 2(11): 518–525. In ARTAVOLᴿ artemisinin has been removed from the Artemisia annua powder to avoid its immunodepressive effect. Artemisinin, dihydroartemisinin, arteanuin B, artemisinic acid strongly inhibit PG2 in vitro Xiaoxin X. Zhu Effects of sesquiterpene, flavonoid and coumarin types of compounds from Artemisia annua L. on production of mediators of angiogenesis Pharmacological Reports Pharmacol Rep, Volume 2013; 65(2): 410–420 ISSN:1734-1140 Wan-Su Kim, Woo Jin Choi, Sunwoo Lee, Woo Joong Kim. Anti-inflammatory, Antioxidant and Antimicrobial Effects of Artemisinin Extracts from Artemisia annua L. Korean J Physiol Pharmacol. 2015 Jan; 19(1): 21–27. Uchechukwu P. Olumayokun A, Olajide, A semi-synthetic derivative of artemisinin, artesunate inhibits prostaglandin E2 production in LPS/IFNγ-activated BV2 microglia. Bioorganic & Medicinal Chemistry, 2014 174726-34 The effect may be less pronounced in vivo where the metabolism of these peroxides is very rapid. And the complexity of prostaglandin generation and inhibition is large. It is known that scopoletin and phytosterols also interfer Awad AB, Toczek J, Fink CS (2004). Phytosterols decrease prostaglandin release in cultured P388D1/MAB macrophages. PLEFA 70:511–520. Acetaminophetamin (Paracetamol) inhibits the PGE₂ production. The hypocholesterolemic agent simvastatin activates the formation of AA from LA Risé P, Marangoni F, Galli C. Regulation of PUFA metabolism: pharmacological and toxicological aspects. Prostaglandins Leukot Essent Fatty Acids. 2002 Aug-Sep;67(2-3):85-9. Prostaglandins also alter the activity of the Na-K ATPase Webb RC, Lockette WE, Vanhoutte PM, Bohr DF. Monovalent ion specificity of the electrogenic sodium pump in vascular smooth muscle. Proc Soc Exp Biol Med. 1981 Mar;166(3):457-61 Host genetic factors and blood characteristics (sickle cell, O blood group, thalassemia, G6DP, PKD) certainly play a role. An effect Patrick Ogwang had noticed in his trials, was an increase in monocytes. This is in line with a thesis from Wake Forest University The role of Omega-3 fatty acids in determining monocyte and macrophage phenotypes, thesis, AL Brown, Wake Forest University, 2011. As fatty fish or fish oil is consumed in low quantities in the U.S. the author tried to determine whether the botanical oil from Echium plantagineum will alter macrophage phenotypes in a murine model. It had been noticed that echium oil reduced inflammation in a waysimilar to fish oil. Using flow cytometry it was found that PUFAs promote macrophage phenotype shifting from the more inflammatory M1 to a less inflammatory M2 phenotype from Wahke Forest University. PUFAs might also affect the invasion by sporozoites. A team from the University of Illinois (Project ILLU-888-918) identified a lipid fraction that inhibits Cryptosporidum parvum sporozoite invasion. Characterization of this lipid revealed it is a long-chain polyunsaturated fatty acid. Only PUFAs which are between 18-20 carbons long, have at least one double bond which is in the cis configuration, and have an unsubstituted carboxyl group are able to block sporozoite invasion. Preliminary data suggest these L-PUFAs inhibit invasion by blocking both sporozoite microneme secretion and gliding motility. Similar results were obtained for Eimeria tenella coccidiosis sporozoite invasion in vitro and in vivo. Crane, M. S. J.; McGaley, C. J., 1991: Eimeria tenella: inhibition of host cell invasion by phospholipase treatment of sporozoites. Experimental Parasitology 72(2): 219-222 The alteration affects the sporozoites and not the host cells. This inhibition of sporozoites by long chain fatty acids applies to many parasitic pathogens of the phylum Apicomplexa like Cryptosporidium parvum, Toxoplasma gondii, and Plasmodium gallinaceum. These parasites commonly infect a variety of vertebrate species and can produce life-threatening diseases, especially in the immunocompromised. This inhibition of sporozoite invasion could be related to the production of the potent bactericidal protein BPI by EPA and DHA. In a US patent Lewis Lambert, Anti-protozoan methods and materials US 20010029245 A1 it is claimed that BPI is also active against Leishmania, Trypanosoma, Plasmodium and Toxoplasma. Through its binding ability BPI derived from DHA and EPA may interfere with the binding of infectuous parasite forms to host cells. An in vivo study with mice, similar to the work of Patrick Ogwang has been made in Nigeria. They studied combinations of the plants Nauclea latifolia, Artocarpus altilis, Murraya koniigii, Enantia chlorantha. Adeleke Clement Adebajo 1,2,* , Samuel Akintunde Odediran 1, Fatimah Abosede Aliyu 1In Vivo Antiplasmodial Potentials of the Combinations of Four Nigerian Antimalarial Plants Molecules 2014, 19(9), 13136-13146; doi:10.3390/molecules190913136 In a prophylactic model the ethanol-water extracts were administred using oral cannula, daily 3 days before infection with Plasmodium berghei, in the chemosuppressive model during 3 days immediately after infection and in the curative model after 3 days of infection during 5 days. For all the plants and/or their mixtures a significant effect on parasitemia was noticed, although not as strong as for the control drug chloroquine. The most striking result is obtained for survival time in the prophylactic approach : on the average a doubling of the survival time compared to much lower effects in the chemosuppressive and curative approaches. This indicates that the herbal treatment has a strong effect on the first steps of the plasmodial invasion and might be less effective on trophozoites ; it highlights the prophylactic and survival effect regular tea consumption. Another trial combining several medicinal plants under the tradename SCAT is described in a thesis from Pakistan. Afzal Ahmad, Clinical Study on Anti – Malarial Herbal Medicine, Ph.D. Thesis, 2005 Hamadard University Karachi The conclusion of a randomized clinical trial was that this herbal medicine is equivalent or even better than amodiaquine in reduction of parasitemia, but superior in avoiding side effects and relapses. Of considerable importance were the observations on gametocyte clearance with SCAT which showed a more rapid reduction in gametocyte numbers. Artemisia plants are rich in linolenic, linoleic acid and arachidonic acid but lack EPA and DHA present in fish oil. However alpha linolenic acid is easily converted in a healthy human into EPA and later into DHA. Linoleic acid is converted into arachidonic acid. This metabolism is slow and half-life of AA, DHA and EPA in human infants is longer than 4 days. For AA it is as long as 45 days. Joshua T. Green, Zhen Liu, and Richard P. Bazinet. Brain phospholipid arachidonic acid half-lives are not altered following 15 weeks of N-3 polyunsaturated fatty acid adequate or deprived dietJ Lipid Res. 2010 Mar; 51(3): 535–543. doi: 10.1194/jlr.M000786 A more elaborate study on DHA and EPA supplementation shows that these fatty acids are rapidly incorporated into plasma lipids. The DHA concentration in plasma plateaus at 350 mmol/ml. The half-life in plasma is 4 days and in whole body 100 days Plourde M, Chouinard-Watkins R, Rioux-Perreault C, Fortier M, Dang MT, Allard MJ, Cunnane SC. Kinetics of 13C-DHA before and during fish-oil supplementation in healthy older individuals. Am J Clin Nutr. 2014 Jul;100(1):105-12. doi: 10.3945/ajcn.113.074708. Plourde M, Chouinard-Watkins R, Vandal M, . Plasma incorporation, apparent retroconversion and beta-oxidation of 13C-docosahexaenoic acid in the elderly. Nutr Metab (Lond) 2011;8:5 Sung-Ha Hong, Ludmila Belayev, Nicolas Bazan, Docohexaeonic acid confers neuroprotection in experimental stroke. J Neurol Sci, 2014, 338, 135-141 In adipose tissue it even has a half-time of 680 as demonstrated by the use of radiactive PUFAs Ana Baylin , Mi Kyung Kim , Paula Tocco. Fasting Whole Blood as a Biomarker of Essential Fatty Acid Intake in Epidemiologic Studies: Comparison with Adipose Tissue and Plasma Am. J. Epidemiol. (15 August 2005) 162 (4): 373-381. doi: 10.1093/aje/kwi213 This explains why the consumption of a few cups of Artemisia infusion or capsules per week might generate a prophylactic effect. As during malaria infection, the concentration of unsaturated fatty acids rapidly declines, their presence and replenishment by the consumption of medicinal herbs may play an important role in prophylaxis and therapy.

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