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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    • "Direct interaction of secondary plant compounds with proteins by the formation of ionic bonds is known to induce changes in conformation and bioactivity. Moreover, it has to be taken into account that green tea contains a complex mixture of catechins and other polyphenolic compounds that could synergistically affect the aforementioned mechanisms [29]. Although the catechins are chemical antioxidants which can quench free radical species and have been demonstrated to increase the resistance to oxidative stress in C. elegans [30], we have previously shown that the prevention of glucose-induced lifespan-reduction by the polyphenol quercetin is independent of antioxidant activities [31]. "
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    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 · 2.35 Impact Factor
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    • "Therefore, laboratories worldwide are trying to produce secondary metabolites from plant tissue cultures for commercial applications (Wink et al., 2005; Alfermann, 2009) as an alternative or addition to plants produced in fields or greenhouses. Lamiaceae include several important species that contain secondary metabolites such as phenolic compounds, flavonoids, iridoids, and terpenoids (Richardson, 1992; Zegorka and Glowniak, 2001; Lu and Yeap-foo, 2002), which have antioxidant , antiinflammatory, antibacterial, and antiviral properties (Van Wyk and Wink, 2004; Wink, 2008). Ziziphora tenuior L. (Lamiaceae) is an annual and aromatic herb of 5–15 cm height (Fig. 1A), and the stem is simple or branched from the base. "
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    ABSTRACT: Ziziphora tenuior L. (Lamiaceae) is an aromatic herb used for its medicinal values against fungi, bacteria. Micropropagation can be used for large-scale multiplication of essential oil producing plants thus avoiding an overexploitation of natural resources. This work aims to develop a reliable protocol for the in vitro propagation of Ziziphora tenuior, and to comparative the antioxidant activity between in vitro and wild plant. The explants were sterilized and cultured on MS medium containing different concentrations of growth regulators naphthalene acetic acid (NAA) or indole–3–butyric acid (IBA) with 0.5 mg/L of kinetin (Kin). callus formation was 70.2% after 45 days of incubation in dark on medium supplemented with 1.5 mg/L of NAA. After one month of callus culture, 5.12 shoots formation on medium supplemented with 2 mg/L BA. for multiplication stage The shoot number was 4.21 shoot and length was 6.17 cm on medium supplemented with 1 mg/L Kin + 0.1 mg/L NAA. DPPH• reagent was used to test the antioxidant activity. The aqueous and methanol extracts showed that the in vitro plants which were treated with 1.5 and 1 mg/L of kin plus 0.1 mg/L of NAA, a strong DPPH• scavenging activity with IC50 of 0.307 and 0.369 mg/ml, respectively. Where The aqueous and methanol extracts of wild plants showed IC50 0.516 and 9.229 mg/ml, respectively. Our results suggested that Plant growth regulators and in vitro Culture conditions increased the antioxidant activity.
    Saudi Journal of Biological Sciences 09/2014; 21(4). DOI:10.1016/j.sjbs.2013.12.002 · 1.26 Impact Factor
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    • "(Burseraceae) leaves and barks were screened for their in vitro antiparasitic activities; among the different extracts tested, the hexane extract of leaves showed moderate antileishmanial activity with IC50 values of 257.40 ± 0.30 μg/mL. This could be due to essential oils present in the hexane extracts as shown previously in the family of Burseraceae [30]. "
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    ABSTRACT: In continuation of our natural and medicinal research programme on tropical rainforest plants, a bioassay guided fractionation of ethanolic extract of leaves of Canarium patentinervium Miq. (Burseraceae Kunth.) led to the isolation of scopoletin (1), scoparone (2), (+)-catechin (3), vomifoliol (4), lioxin (5), and syringic acid (6). All the compounds exhibited antiacetylcholinesterase activity with syringic acid, a phenolic acid exhibiting good AChE inhibition (IC50 29.53 ± 0.19 μ g/mL). All compounds displayed moderate antileishmanial activity with scopoletin having the highest antileishmanial activity (IC50 163.30 ± 0.32 μ g/mL). Given the aforementioned evidence, it is tempting to speculate that Canarium patentinervium Miq. represents an exciting scaffold from which to develop leads for treatment of neurodegenerative and parasitic diseases.
    BioMed Research International 05/2014; 2014:903529. DOI:10.1155/2014/903529 · 3.17 Impact Factor
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