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.
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ABSTRACT: Despite the great marketing success, most physicians attribute poor efficacy to herbals. This perception is due to two situations that are an integral part of the herbal topic. The first is the poor phytochemical reproducibility obtained during the production process of herbal extracts, as herbal extracts are not always standardized in the whole manufacturing process, but only in their titer. The second problem is linked to the evolution of important enzymatic systems: cytochromes and ABC proteins. They are both enzyme classes with detoxifying properties and seem to have evolved from the molecular mould provided by active plant substances. During the evolution, as still happens today, polyphenols, saponins, terpenes, and alkaloids were ingested together with food. They do not possess any nutritional value but seem to be provided with a potential pharmacological activity. Cytochromes and ABC proteins, which evolved over time to detoxify food from vegetable chemical "actives," now seem to limit the action of herbal derivatives. The comprehension of these 2 events may explain the origin of the widespread scepticism of physicians about herbal medicine and suggests that, after correct herbal standardization, use of antagonists of cytochromes and ABC systems will make it possible to recover their pharmacological potential.TheScientificWorldJournal. 01/2014; 2014:732045.
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ABSTRACT: The chemical compositions of essential oils from cumin and coriander fruits were investigated using GLC and GLC/MS. Forty six compounds were identified in both oils. The major constituents of cumin oil were identified as γ-terpinene (22.7%), β-pinene (19.2%), cuminaldehyde (18.0%), p-cymene (11.5%), whereas linalool (70.43%) is the most abundant component in coriander oil. The antioxidant and anti-inflammatory activity and cytotoxicity of the essential oils were assessed. Cumin oil exhibited stronger antioxidant activity (IC 50 values, 2.37 mg/ml for DPPH • assay and 27.7 µg/ml for OH • assay) as compared to the coriander oil. Both oils inhibited the PGE 2 production in lipopolysaccharide (LPS) stimulated HepG-2 cells. They also inhibited soybean lipoxygenase (5-LOX). Cumin oil (20 µg/ml) caused a 22.44% reduction in PGE 2 level after treatment of the cells. IC 50 values for lipoxygenase inhibition were 35.8 and 38.6 µg/ml for cumin and coriander oils, respectively. Cumin oil exhibited substantial antiproliferative activity against HepG-2 with an IC 50 value of 31.4 µg/ml, whereas coriander was less active (IC 50 120.4 µg/ml).The natural Products Journal. 06/2014; 4(1):63-69.
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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 01/2014; 2014:903529. · 2.71 Impact Factor