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      Whole plant extracts versus single compounds for the treatment of malaria: synergy and positive interactions

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          Abstract

          Background

          In traditional medicine whole plants or mixtures of plants are used rather than isolated compounds. There is evidence that crude plant extracts often have greater in vitro or/and in vivo antiplasmodial activity than isolated constituents at an equivalent dose. The aim of this paper is to review positive interactions between components of whole plant extracts, which may explain this.

          Methods

          Narrative review.

          Results

          There is evidence for several different types of positive interactions between different components of medicinal plants used in the treatment of malaria. Pharmacodynamic synergy has been demonstrated between the Cinchona alkaloids and between various plant extracts traditionally combined. Pharmacokinetic interactions occur, for example between constituents of Artemisia annua tea so that its artemisinin is more rapidly absorbed than the pure drug. Some plant extracts may have an immunomodulatory effect as well as a direct antiplasmodial effect. Several extracts contain multidrug resistance inhibitors, although none of these has been tested clinically in malaria. Some plant constituents are added mainly to attenuate the side-effects of others, for example ginger to prevent nausea.

          Conclusions

          More clinical research is needed on all types of interaction between plant constituents. This could include clinical trials of combinations of pure compounds (such as artemisinin + curcumin + piperine) and of combinations of herbal remedies (such as Artemisia annua leaves + Curcuma longa root + Piper nigum seeds). The former may enhance the activity of existing pharmaceutical preparations, and the latter may improve the effectiveness of existing herbal remedies for use in remote areas where modern drugs are unavailable.

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          Most cited references76

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          Flavonoids as antioxidants.

          Flavonoids are phenolic substances isolated from a wide range of vascular plants, with over 8000 individual compounds known. They act in plants as antioxidants, antimicrobials, photoreceptors, visual attractors, feeding repellants, and for light screening. Many studies have suggested that flavonoids exhibit biological activities, including antiallergenic, antiviral, antiinflammatory, and vasodilating actions. However, most interest has been devoted to the antioxidant activity of flavonoids, which is due to their ability to reduce free radical formation and to scavenge free radicals. The capacity of flavonoids to act as antioxidants in vitro has been the subject of several studies in the past years, and important structure-activity relationships of the antioxidant activity have been established. The antioxidant efficacy of flavonoids in vivo is less documented, presumably because of the limited knowledge on their uptake in humans. Most ingested flavonoids are extensively degraded to various phenolic acids, some of which still possess a radical-scavenging ability. Both the absorbed flavonoids and their metabolites may display an in vivo antioxidant activity, which is evidenced experimentally by the increase of the plasma antioxidant status, the sparing effect on vitamin E of erythrocyte membranes and low-density lipoproteins, and the preservation of erythrocyte membrane polyunsaturated fatty acids. This review presents the current knowledge on structural aspects and in vitro antioxidant capacity of most common flavonoids as well as in vivo antioxidant activity and effects on endogenous antioxidants.
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            Antioxidant and antiradical activities of flavonoids.

            The relationship between the structure of 42 flavonoids and their antioxidant and antiradical activities was elucidated by heat-induced oxidation in a beta-carotene and linoleic acid system and by the 1,1-diphenyl-2-picrylhydrazyl decoloration test. From seven structurally divergent groups of flavonoids, only flavonols with a free hydroxyl group at the C-3 position of the flavonoid skeleton showed high inhibitory activity to beta-carotene oxidation. Antiradical activity depended on the presence of a flavonol structure or free hydroxyl group at the C-4' position. The effect of the 4'-hydroxyl was strongly modified by other structural features, such as the presence of free hydroxyls at C-3 and/or C-3' and a C2-C3 double bond.
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              Zingiberis rhizoma: a comprehensive review on the ginger effect and efficacy profiles.

              Zingiberis rhizoma is used as a broadspectrum antiemetic. We, therefore, conducted a comprehensive review of the literature to summarize the pharmacological and clinical effects of this popular plant material. Although clinical and experimental studies suggest that ginger has some antiemetic properties, clinical evidence beyond doubt is only available for pregnancy-related nausea and vomiting. Meta-analyses could not demonstrate the postoperative antiemetic effectiveness, and effect in motion sickness or nausea/vomiting of other ethiology. It also remains to be confirmed that proprietary ginger preparations are clinically useful to alleviate osteoarthritic or other pain, although there is no doubt that ginger constituents interfere with the inflammatory cascade and the vanilloid nociceptor. Ginger exerts in vitro antioxidative, antitumorigenic and immunomodulatory effects and is an effective antimicrobial and antiviral agent. Animal studies demonstrate effects on the gastrointestinal tract, the cardiovascular system, on experimental pain and fever, antioxidative, antilipidemic and antitumor effects, as well as central and other effects. The most relevant human pharmacological studies require a confirmatory study to exclude interaction of ginger preparations with platelet aggregation. Pharmacokinetic data are only available for [6]-gingerol and zingiberene. Preclinical safety data do not rule out potential toxicity, which should be monitored especially following ginger consumption over longer periods.
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                Author and article information

                Conference
                Malar J
                Malaria Journal
                BioMed Central
                1475-2875
                2011
                15 March 2011
                : 10
                : Suppl 1
                : S4
                Affiliations
                [1 ]IMRA, Madagascar
                [2 ]University of Bradford, UK
                [3 ]RITAM, Oxford, UK
                [4 ]Dept of Primary Health Care, University of Oxford, UK
                [5 ]Fiocruz, Brazil
                Article
                1475-2875-10-S1-S4
                10.1186/1475-2875-10-S1-S4
                3059462
                21411015
                0dde54dd-bbcd-4051-b662-6880d7330d80
                Copyright ©2011 Rasoanaivo et al; licensee BioMed Central Ltd.

                This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Reviews

                Infectious disease & Microbiology
                Infectious disease & Microbiology

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