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      Anti-Parasitic Activities of Allium sativum and Allium cepa against Trypanosoma b. brucei and Leishmania tarentolae

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          Abstract

          Background: Garlics and onions have been used for the treatment of diseases caused by parasites and microbes since ancient times. Trypanosomiasis and leishmaniasis are a concern in many areas of the world, especially in poor countries. Methods: Trypanosoma brucei brucei and Leishmania tarentolae were used to investigate the anti-parasitic effects of dichloromethane extracts of Allium sativum (garlic) and Allium cepa (onion) bulbs. As a confirmation of known antimicrobial activities, they were studied against a selection of G-negative, G-positive bacteria and two fungi. Chemical analyses were performed using high-performance liquid chromatography (HPLC) and electrospray ionization-mass spectrometry (LC-ESI-MS/MS). Results: Chemical analyses confirmed the abundance of several sulfur secondary metabolites in garlic and one (zwiebelane) in the onion extract. Both extracts killed both types of parasites efficiently and inhibited the Trypanosoma brucei trypanothione reductase irreversibly. In addition, garlic extract decreased the mitochondrial membrane potential in trypanosomes. Garlic killed the fungi C. albicans and C. parapsilosis more effectively than the positive control. The combinations of garlic and onion with common trypanocidal and leishmanicidal drugs resulted in a synergistic or additive effect in 50% of cases. Conclusion: The mechanism for biological activity of garlic and onion appears to be related to the amount and the profile of sulfur-containing compounds. It is most likely that vital substances inside the parasitic cell, like trypanothione reductase, are inhibited through disulfide bond formation between SH groups of vital redox compounds and sulfur-containing secondary metabolites.

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          Most cited references31

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          Evaluation of combination chemotherapy: integration of nonlinear regression, curve shift, isobologram, and combination index analyses.

          Isobologram and combination index (CI) analyses are the two most popular methods for evaluating drug interactions in combination cancer chemotherapy. As the commonly used CI-based software program uses linear regression, our first objective was to evaluate the effects of logarithmic data transformation on data analysis and conclusions. Monte-Carlo simulations were conducted with experimentally relevant parameter values to generate error-containing effect or concentration-effect data of single agents and combinations. The simulated data were then analyzed with linear and nonlinear regression. The results showed that data transformation reduced the accuracy and precision of the regression-derived IC(50), curve shape parameter and CI values. Furthermore, as neither isobologram nor CI analyses provide output of concentration-effect curves for investigator evaluation, our second objective was to develop a method and the associated computer program/algorithm to (a) normalize drug concentrations in IC(50) equivalents and thereby enable simultaneous presentation of the curves for single agents and combinations in a single plot for visual inspection of potential curve shifts, (b) analyze concentration-effect data with nonlinear regression, and (c) use the curve shift analysis simultaneously with isobologram and CI analyses. The applicability of this method was shown with experimentally obtained data for single agent doxorubicin and suramin and their combinations in cultured tumor cells. In summary, this method, by incorporating nonlinear regression and curve shift analysis, although retaining the attractive features of isobologram and CI analyses, reduced the potential errors introduced by logarithmic data transformation, enabled visual inspection of data variability and goodness of fit of regression analysis, and simultaneously provided information on the extent of drug interaction at different combination ratios/concentrations and at different effect levels.
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            Metabolism and functions of trypanothione in the Kinetoplastida.

            Trypanosomatids differ from all other organisms in their ability to conjugate the sulfur-containing tripeptide, glutathione, and the polyamine, spermidine, to form trypanothione [N1,N8-bis(glutathionyl)spermidine]. Together with the NADPH-dependent flavoprotein, trypanothione reductase, the dithiol form of trypanothione provides an intracellular reducing environment in these parasites, substituting for glutathione and glutathione reductase found in the mammalian host. Trypanothione and its related enzymes are involved in defense against damage by oxidants, certain heavy metals, and possibly xenobiotics. Trypanothione and its metabolic precursor, glutathionylspermidine, are also implicated in the modulation of spermidine levels during growth. Several existing trypanocidal drugs interact with the trypanothione system, suggesting that trypanothione metabolism may be a good target for the development of new drugs. The purification and properties of three key enzymes (glutathionylspermidine synthetase, trypanothione synthetase, and trypanothione reductase) are discussed, and the catalytic mechanism, substrate-specificity, and the three-dimensional structure of trypanothione reductase are compared to that of glutathione reductase.
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              Medicinal Plants: A Source of Anti-Parasitic Secondary Metabolites

              This review summarizes human infections caused by endoparasites, including protozoa, nematodes, trematodes, and cestodes, which affect more than 30% of the human population, and medicinal plants of potential use in their treatment. Because vaccinations do not work in most instances and the parasites have sometimes become resistant to the available synthetic therapeutics, it is important to search for alternative sources of anti-parasitic drugs. Plants produce a high diversity of secondary metabolites with interesting biological activities, such as cytotoxic, anti-parasitic and anti-microbial properties. These drugs often interfere with central targets in parasites, such as DNA (intercalation, alkylation), membrane integrity, microtubules and neuronal signal transduction. Plant extracts and isolated secondary metabolites which can inhibit protozoan parasites, such as Plasmodium, Trypanosoma, Leishmania, Trichomonas and intestinal worms are discussed. The identified plants and compounds offer a chance to develop new drugs against parasitic diseases. Most of them need to be tested in more detail, especially in animal models and if successful, in clinical trials.
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                Author and article information

                Journal
                Medicines (Basel)
                Medicines (Basel)
                medicines
                Medicines
                MDPI
                2305-6320
                21 April 2018
                June 2018
                : 5
                : 2
                : 37
                Affiliations
                Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany; sobeh@ 123456uni-heidelberg.de (M.S.); m.braun@ 123456uni-heidelberg.de (M.S.B.)
                Author notes
                [* ]Correspondence: krstin@ 123456uni-heidelberg.de (S.K.); wink@ 123456uni-heidelberg.de (M.W.); Tel.: +49-6221-544880 (S.K. & M.W.); Fax: +49-6221-544884 (S.K. & M.W.)
                Author information
                https://orcid.org/0000-0002-2719-8534
                https://orcid.org/0000-0002-5735-4067
                https://orcid.org/0000-0002-7875-4510
                Article
                medicines-05-00037
                10.3390/medicines5020037
                6023319
                29690511
                2b5a0f9c-8159-4d00-b5b0-650831c569fc
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 29 March 2018
                : 17 April 2018
                Categories
                Article

                garlic,onion,allium sativum,allium cepa,anti-parasitic activity,trypanothione,trypanothione reductase

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