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Trypanosoma brucei Inhibition by Essential Oils from Medicinal and Aromatic Plants Traditionally Used in Cameroon (Azadirachta indica, Aframomum melegueta, Aframomum daniellii, Clausena anisata, Dichrostachys cinerea and Echinops giganteus)

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      Abstract

      Essential oils are complex mixtures of volatile components produced by the plant secondary metabolism and consist mainly of monoterpenes and sesquiterpenes and, to a minor extent, of aromatic and aliphatic compounds. They are exploited in several fields such as perfumery, food, pharmaceutics, and cosmetics. Essential oils have long-standing uses in the treatment of infectious diseases and parasitosis in humans and animals. In this regard, their therapeutic potential against human African trypanosomiasis (HAT) has not been fully explored. In the present work, we have selected six medicinal and aromatic plants ( Azadirachta indica, Aframomum melegueta, Aframomum daniellii, Clausena anisata, Dichrostachys cinerea, and Echinops giganteus) traditionally used in Cameroon to treat several disorders, including infections and parasitic diseases, and evaluated the activity of their essential oils against Trypanosma brucei TC221. Their selectivity was also determined with Balb/3T3 (mouse embryonic fibroblast cell line) cells as a reference. The results showed that the essential oils from A. indica, A. daniellii, and E. giganteus were the most active ones, with half maximal inhibitory concentration (IC 50) values of 15.21, 7.65, and 10.50 µg/mL, respectively. These essential oils were characterized by different chemical compounds such as sesquiterpene hydrocarbons, monoterpene hydrocarbons, and oxygenated sesquiterpenes. Some of their main components were assayed as well on T. brucei TC221, and their effects were linked to those of essential oils.

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      Natural products as sources of new drugs over the period 1981-2002.

      This review is an updated and expanded version of a paper that was published in this journal in 1997. The time frame has been extended in both directions to include the 22 years from 1981 to 2002, and a new secondary subdivision related to the natural product source but applied to formally synthetic compounds has been introduced, using the concept of a "natural product mimic" or "NM" to join the original primary divisions. From the data presented, the utility of natural products as sources of novel structures, but not necessarily the final drug entity, is still alive and well. Thus, in the area of cancer, the percentage of small molecule, new chemical entities that are nonsynthetic has remained at 62% averaged over the whole time frame. In other areas, the influence of natural product structures is quite marked, particularly in the antihypertensive area, where of the 74 formally synthetic drugs, 48 can be traced to natural product structures/mimics. Similarly, with the 10 antimigraine drugs, seven are based on the serotonin molecule or derivatives thereof. Finally, although combinatorial techniques have succeeded as methods of optimizing structures and have, in fact, been used in the optimization of a number of recently approved agents, we have not been able to identify a de novo combinatorial compound approved as a drug in this time frame.
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        Continuous cultivation of Trypanosoma brucei blood stream forms in a medium containing a low concentration of serum protein without feeder cell layers.

         H Hirumi,  K Hirumi (1989)
        Blood stream forms (BSF) of Trypanosoma brucei brucei GUT at 3.1 were propagated in vitro in the absence of feeder layer cells at 37 C, using a modified Iscove's medium (HMI-18). The medium was supplemented with 0.05 mM bathocuproine sulfonate, 1.5 mM L-cysteine, 1 mM hypoxanthine, 0.2 mM 2-mercaptoethanol, 1 mM sodium pyruvate. 0.16 mM thymidine, and 20% (v/v) Serum Plus (SP) (Hazleton Biologics, Lenexa, Kansas). The latter contained a low level of serum proteins (13 micrograms/ml). Each primary culture was initiated by placing 3.5-4 x 10(6) BSFs isolated from infected mice in a flask containing 5 ml of the medium (HMI-9) supplemented with 10% fetal bovine serum (FBS) and 10% SP. The cultures were maintained by replacing the medium every 24 hr for 5-7 days. During this period, many BSFs died. However, from day 4 onward, long slender BSFs increased in number. On days 5-7, trypanosome suspensions were pooled and cell debris was removed by means of diethylaminoethyl cellulose (DE52) column chromatography. Blood stream forms then were collected by centrifugation, resuspended in fresh medium at 7-9 x 10(5)/ml, and transferred to new flasks. Subcultures were maintained by readjusting the BSF density to 7-9 x 10(5)/ml every 24 hr. Concentrations of FBS were reduced gradually at 5-7-day intervals by alternating the amounts of FBS and SP in HMI-9 with 5% FBS and 15% SP, with 2% FBS and 18% SP, and finally with 20% SP (HMI-18). By this method, 2-3 x 10(6) VSFs/ml were obtained consistently every 24 hr. for more than 80 days.(ABSTRACT TRUNCATED AT 250 WORDS)
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          Human African trypanosomiasis.

          Human African trypanosomiasis (sleeping sickness) occurs in sub-Saharan Africa. It is caused by the protozoan parasite Trypanosoma brucei, transmitted by tsetse flies. Almost all cases are due to Trypanosoma brucei gambiense, which is indigenous to west and central Africa. Prevalence is strongly dependent on control measures, which are often neglected during periods of political instability, thus leading to resurgence. With fewer than 12 000 cases of this disabling and fatal disease reported per year, trypanosomiasis belongs to the most neglected tropical diseases. The clinical presentation is complex, and diagnosis and treatment difficult. The available drugs are old, complicated to administer, and can cause severe adverse reactions. New diagnostic methods and safe and effective drugs are urgently needed. Vector control, to reduce the number of flies in existing foci, needs to be organised on a pan-African basis. WHO has stated that if national control programmes, international organisations, research institutes, and philanthropic partners engage in concerted action, elimination of this disease might even be possible. Copyright 2010 Elsevier Ltd. All rights reserved.
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            Author and article information

            Affiliations
            [1 ]School of Pharmacy, University of Camerino, 62032 Camerino, Italy; landry.ngahangkamte@ 123456unicam.it (S.L.N.K.); loredana.cappellacci@ 123456unicam.it (L.C.); filippo.maggi@ 123456unicam.it (F.M.)
            [2 ]Department of Medical Biochemistry and Biophysics, Umeå University, 90187 Umeå, Sweden; farahnaz.ranjbarian@ 123456umu.se (F.R.); anders.hofer@ 123456umu.se (A.H.)
            [3 ]Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK; g.campagnaro.1@ 123456research.gla.ac.uk
            [4 ]Laboratory of Medicinal Plant Biochemistry, Food Science and Nutrition, Department of Biochemistry, Faculty of Sciences, University of Dschang, Dschang POX 67, Cameroon; prbiapa@ 123456yahoo.fr (P.C.B.N.); helenembuntcha@ 123456yahoo.fr (H.M.); woverly91@ 123456yahoo.fr (V.W.); womeni@ 123456yahoo.fr (H.M.W.)
            [5 ]Laboratory of Environmental and Applied Chemistry, Faculty of Science, University of Dschang, Dschang POX 67, Cameroon; tapondjou2001@ 123456yahoo.fr
            [6 ]Instituto de Física, Universidad de Antioquia, Medellín AA 1226, Colombia; cristiano.giordani@ 123456udea.edu.co
            [7 ]School of Science and Technology, Chemistry Division, University of Camerino, 62032 Camerino, Italy; luciano.barboni@ 123456unicam.it
            [8 ]Department of Agriculture, Food and Environment, University of Pisa, 56124 Pisa, Italy; benelli.giovanni@ 123456gmail.com
            Author notes
            [* ]Correspondence: riccardo.petrelli@ 123456unicam.it ; Tel.: +39-0737402284; Fax: +39-0737637345
            [†]

            These authors contributed equally to this study.

            Contributors
            Role: Academic Editor
            Journal
            Int J Environ Res Public Health
            Int J Environ Res Public Health
            ijerph
            International Journal of Environmental Research and Public Health
            MDPI
            1661-7827
            1660-4601
            06 July 2017
            July 2017
            : 14
            : 7
            28684709
            5551175
            10.3390/ijerph14070737
            ijerph-14-00737
            (Academic Editor)
            © 2017 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/).

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