Evolutionary advantage and molecular modes of action of multi-component mixtures used in phytomedicine.
ABSTRACT Plants use complex mixtures of secondary compounds (SM) of different structural classes to protect themselves against herbivores, bacteria, fungi and viruses. These complex mixtures may contain SM, which are specific for a single target (monotarget SM). A majority of SM, however, can interfere with several targets (multitarget SM) in a pleiotropic fashion. The composition of such extracts appears to be optimised, since the components are not only additive but apparently synergistic in their bioactivity. Synergism can be achieved by inhibiting the xenobiotics inactivating activities of animals and microbes (MDR, CYP), by facilitating the uptake of polar SM across biomembranes and/or by affecting several important organs in animals concomitantly. Phytotherapy employs equally complex extracts of medicinal plants. Arguments were put together that the utilisation of complex mixtures with pleiotropic agents presents a unique therapeutic approach with many advantages over monotarget compounds. Mixtures of multitarget SM, used in phytotherapy include phenolics, tannins, mono- and sequiterpenes, saponins, iridoid glucosides and anthraquinones, but only few of them alkaloids or other toxic monotarget SM.Multitarget effects are caused by SM, which can modulate the three-dimensional structure of proteins (and thus their function), by interfering with DNA/RNA (especially gene expression) or membrane permeability. In addition, complex extracts may contain synergists, which can inhibit MDR, cytochrome P450 or enhance absorption and thus bioavailability of active metabolites. The molecular modes of action are reviewed for the main groups of secondary metabolites.
SourceAvailable from: Dorothé Jenni Deusing[Show abstract] [Hide abstract]
ABSTRACT: Hyperglycemia is a hallmark of diabetes mellitus which leads to the onset of complications in the long term. Green tea through its high content of polyphenolic catechins, on the other hand, is suggested to prevent or at least delay such detrimental complications. In the present study we fed the nematode Caenorhabditis elegans on a liquid medium supplemented with 10mM glucose in the absence or presence of a catechin-enriched green tea extract (CEGTE). After exposure of young adults for 48h survival was subsequently measured under heat stress at 37°C. Whereas CEGTE at 0.01% did not affect the survival of wild type nematodes, it completely reversed the glucose-induced survival reduction. Those effects were not achieved through the monomeric catechins included in CEGTE. RNA interference (RNAi) for sir-2.1 not only prevented the survival extension by CEGTE under simultaneous glucose exposure but caused a further reduction of survival. Likewise, the knockdown of uba-1, encoding the only E1-ubiquitin-activating enzyme in C. elegans, proved that UBA-1 is essential for the survival extension by CEGTE and that its loss of function changes CEGTE from a survival extending into a survival reducing extract. Stimulation of the proteasome by CEGTE was finally proven through measurements of the proteolytic cleavage of a fluorogenic peptide substrate. To conclude, our studies provide evidence that CEGTE reverses glucose-induced damage in C. elegans through activation of adaptive responses mediated by SIR-2.1 and proteasomal degradation. The hormetic mode of action is revealed by a reduction of survival once the adaptive processes were blocked. Copyright © 2015. Published by Elsevier B.V.Fitoterapia 03/2015; 102. DOI:10.1016/j.fitote.2015.03.005 · 2.22 Impact Factor
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ABSTRACT: The genus Warburgia (Canellaceae) is represented by several medicinal trees found exclusively on the African continent. Traditionally, extracts and products produced from Warburgia species are regarded as important natural African antibiotics and have been used extensively as part of traditional healing practices for the treatment of fungal, bacterial and protozoal infections in both humans and animals. To collate and review the fragmented information on the ethnobotany, phytochemistry and biological activities of ethnomedicinally important Warburgia species and present recommendations for future research. Peer-reviewed articles using "Warburgia" as search term ("all fields") were retrieved from Scopus, ScienceDirect, SciFinder and Google Scholar with no specific time frame set for the search. In addition, various books were consulted that contained botanical and ethnopharmacological information. The ethnopharmacology, phytochemistry and biological activity of Warburgia are reviewed. Most of the biological activities are attributed to the drimane sesquiterpenoids, including polygodial, warburganal, muzigadial, mukaadial and ugandensial, flavonoids and miscellaneous compounds present in the various species. In addition to anti-infective properties, Warburgia extracts are also used to treat a wide range of ailments, including stomach aches, fever and headaches, which may also be a manifestation of infections. The need to record anecdotal evidence is emphasized and conservation efforts are highlighted to contribute to the protection and preservation of one of Africa's most coveted botanical resources. Copyright © 2015. Published by Elsevier Ireland Ltd.Journal of Ethnopharmacology 02/2015; DOI:10.1016/j.jep.2015.02.021 · 2.94 Impact Factor
03/2015; 2(1):28-46. DOI:10.3390/medicines2010028