Evolutionary Advantage and Molecular Modes of Action of Multi- Component Mixtures Used in Phytomedicine

Heidelberg University, Institute of Pharmacy and Molecular Biotechnology, INF 364, 69120 Heidelberg, Germany.
Current Drug Metabolism (Impact Factor: 2.98). 01/2009; 9(10):996-1009.
Source: PubMed


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.

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    • "Majority of thoroughly studied medicinal plants contain broad spectrum of bioactive compounds (Efferth and Koch, 2011) with each phytochemicals have different antimicrobial mode (Simoes et al., 2009). Multitarget effects of phytochemicals include alteration in structure and function of proteins, interference with synthesis of DNA or RNA or proteins, disruption of the cell membrane and change in its function, inhibition of cytochrome P450 or enhanced absorption and thus bioavailability of active metabolites (Efferth and Koch, 2011; Wink, 2008). It has been shown that extracts of different plants contain inhibitors of efflux pumps in bacteria (Garvey et al., 2011; Hsieh et al., 1998), therefore can help fighting multidrug resistance by inhibiting the action of efflux pumps. "
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    • "Natural molecules and products reemerge as promising sources of complex multitarget mixtures that are used as alternative therapeutic agents for various conditions, including infections and chronic diseases [1] [2], such as oral diseases [3] [4] [5] or digestive cancers [6]. Amphipterygium adstringens Schiede ex Schlecht (Julianaceae ) is an endemic species in Mexico commonly known as " cuachalalate. "
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