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      Chemical composition, anti-Trypanosoma cruzi and cytotoxic activities of the essential oil from green fruits of Protium ovatum (BURSERACEAE) Translated title: Composição química, atividades anti-Trypanosoma cruzi e citotóxica do óleo essencial dos frutos verdes de Protium ovatum (BURSERACEAE)

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          Abstract

          Abstract Chagas disease is a major neglected tropical disease caused by Trypanosoma cruzi. It has been treated with the antiparasitic drugs nifurtimox and benzonidazole, which cause several side effects. The market for natural products has considerably grown lately and the use of plants has become an alternative to the development of novel drugs to cure the disease. Therefore, this study aimed at describing the chemical analysis of the essential oil from green fruits of Protium ovatum and evaluating their trypanocidal and cytotoxic potential. The essential oil was obtained by Clevenger hydrodistillation whereas its chemical composition was determined by gas chromatography coupled to mass spectrometry (GC-MS). The major compounds found in the essential oil from green fruits of P. ovatum were ß-myrcene (62.0 %), a-pinene (11.3 %) and limonene (7.3 %). To the best of our knowledge, this was the first time that the chemical composition of the essential oil from green fruits of P. ovatum was described. Results showed that the essential oil had strong trypanocidal activity against trypomastigote forms of theY strain of Trypanosoma cruzi (IC50 = 1.2 µg/mL). In addition, the essential oil from green fruits of P. ovatum did not display cytotoxicity against LLCMK2 adherent epithelial cell at the concentration range under analysis (CC50 = 550.3 µg/mL). As a result, it is an excellent option for the development of novel antiparasitic drugs.

          Translated abstract

          Resumo A doença de Chagas é uma das principais doenças tropicais negligenciadas causadas pelo Trypanosoma cruzi, e em seu tratamento utilizam-se medicamentos como o nifurtimox e o benzonidazol, que causam vários efeitos colaterais. O mercado de produtos naturais tem aumentado consideravelmente nos últimos anos, e o uso das plantas continua sendo uma alternativa para o desenvolvimento de novos medicamentos para cura de doenças. Portanto, este estudo aborda a composição química do óleo essencial dos frutos verdes de Protium ovatum e a avaliação de seus potenciais tripanocida e citotóxico. O óleo essencial foi obtido por hidrodestilação, utilizando o aparato do tipo Clevenger. A composição química foi determinada por cromatografia gasosa acoplada ao espectrômetro de massas (CG-EM). Os principais compostos encontrados no óleo essencial dos frutos verdes de P. ovatum foram: ß-mirceno (62,0 %), a-pineno (11,3 %) e limoneno (7,3 %). Este é o primeiro relato da composição química do óleo essencial obtido a partir de frutos verdes de P. ovatum. Os resultados mostraram que o óleo essencial analisado apresenta forte atividade tripanocida contra as formas tripomastigota da cepa Y do Trypanosoma cruzi (IC50 = 1,2 µg/mL). O óleo essencial exibiu ainda moderada citotoxidade frente à linhagem LLCMK2 na concentração avaliada (CC50 = 550,3 µg/mL). Em suma, o óleo essencial dos frutos verdes de P. ovatum pode ser considerado uma fonte alternativa para o desenvolvimento de novos medicamentos antiparasitários.

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          Most cited references26

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          Efficacy, safety, quality control, marketing and regulatory guidelines for herbal medicines (phytotherapeutic agents)

          This review highlights the current advances in knowledge about the safety, efficacy, quality control, marketing and regulatory aspects of botanical medicines. Phytotherapeutic agents are standardized herbal preparations consisting of complex mixtures of one or more plants which contain as active ingredients plant parts or plant material in the crude or processed state. A marked growth in the worldwide phytotherapeutic market has occurred over the last 15 years. For the European and USA markets alone, this will reach about $7 billion and $5 billion per annum, respectively, in 1999, and has thus attracted the interest of most large pharmaceutical companies. Insufficient data exist for most plants to guarantee their quality, efficacy and safety. The idea that herbal drugs are safe and free from side effects is false. Plants contain hundreds of constituents and some of them are very toxic, such as the most cytotoxic anti-cancer plant-derived drugs, digitalis and the pyrrolizidine alkaloids, etc. However, the adverse effects of phytotherapeutic agents are less frequent compared with synthetic drugs, but well-controlled clinical trials have now confirmed that such effects really exist. Several regulatory models for herbal medicines are currently available including prescription drugs, over-the-counter substances, traditional medicines and dietary supplements. Harmonization and improvement in the processes of regulation is needed, and the general tendency is to perpetuate the German Commission E experience, which combines scientific studies and traditional knowledge (monographs). Finally, the trend in the domestication, production and biotechnological studies and genetic improvement of medicinal plants, instead of the use of plants harvested in the wild, will offer great advantages, since it will be possible to obtain uniform and high quality raw materials which are fundamental to the efficacy and safety of herbal drugs.
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            Chemical composition and antiprotozoal activities of Colombian Lippia spp essential oils and their major components

            The chemical composition and biological activities of 19 essential oils and seven of their major components were tested against free and intracellular forms of Leishmania chagasi and Trypanosoma cruzi parasites as well as Vero and THP-1 mammalian cell lines. The essential oils were obtained from different species of Lippia, a widely distributed genus of Colombian plants. They were extracted by microwave radiation-assisted hydro-distillation and characterised by GC-FID and GC-MS. The major components were geranial, neral, limonene, nerol, carvacrol, p-cymene, γ-terpinene, carvone and thymol. The essential oil of Lippia alba exhibited the highest activity against T. cruzi epimastigotes and intracellular amastigotes with an IC50 of 5.5 μg/mL and 12.2 μg/mL, respectively. The essential oil of Lippia origanoides had an IC50 of 4.4 μg/mL in L. chagasi promastigotes and exhibited no toxicity in mammalian cells. Thymol (IC50 3.2 ± 0.4 μg/mL) and S-carvone (IC50 6.1 ± 2.2 μg/mL), two of the major components of the active essential oils, were active on intracellular amastigotes of T. cruziinfected Vero cells, with a selective index greater than 10. None of the essential oils or major components tested in this study was active on amastigotes of L. chagasi infected THP-1 cells.
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              Terpenes from Copaifera demonstrated in vitro antiparasitic and synergic activity.

              To discover new possible therapies for Chagas' disease, we evaluated against all Trypanosoma cruzi life stages the in vitro trypanocidal and synergistic activity of terpenes isolated from Copaifera oleoresins collected in the Amazon and investigated their possible mechanism of action. Seven acid diterpenes and one sesquiterpene were tested. Terpenes promoted changes in oxidative metabolism followed by autophagic processes in the parasite cell leading to selective death. Furthermore, they were more effective against replicative forms, in particular amastigotes. A synergistic effect occurred. Cytotoxicity to erythrocytes and nucleated cells was moderate. This is the first study showing synergic activity between two terpenes against T. cruzi. Combinations of natural compounds can show high activity and may lead to new alternative treatments in the future. © 2012 American Chemical Society
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                Author and article information

                Journal
                rbf
                Revista Brasileira de Fruticultura
                Rev. Bras. Frutic.
                Sociedade Brasileira de Fruticultura (Jaboticabal, SP, Brazil )
                0100-2945
                1806-9967
                2018
                : 40
                : 1
                : e-794
                Affiliations
                [06] Minas Gerais orgnameInstituto Federal do Sul de Minas Gerais Brazil mayker.miranda@ 123456ifsuldeminas.edu.br
                [04] Minas Gerais orgnameInstituto Federal do Sudeste de Minas Gerais Brazil criscazal@ 123456yahoo.com.br
                [05] orgnameInstituto Federal do Mato Grosso do Sul Brasil allex_fonseca@ 123456yahoo.com.br
                [02] Goiás orgnameInstituto Federal Goiano Brazil cassiacefetrv@ 123456gmail.com
                [01] Goiás orgnameInstituto Federal Goiano Brazil elisangelaborges49@ 123456hotmail.com
                [03] São Paulo orgnameUniversidade de Franca Brazil viviane.sampaio@ 123456unifran.edu.br
                Article
                S0100-29452018000106001 S0100-2945(18)04000106001
                10.1590/0100-29452018794
                13f85db3-41d0-490f-823b-85fd266f350d

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 11 July 2017
                : 27 October 2016
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 26, Pages: 0
                Product

                SciELO Brazil

                Categories
                Human Health

                análise citotóxica,Protium ovatum,ß-myrcene,fruits,essential oil,Trypanosoma cruzi,cytotoxic analysis,ß-mirceno,frutos,óleo essencial

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