Nejvíce citovaný článek - PubMed ID 22980846
Iron reduction potentiates hydroxyl radical formation only in flavonols
Various medicinal plants find their use in cough treatment, based on traditions and long-term experience. Pharmacological principles of their action, however, are much less known. Herbal drugs usually contain a mixture of potentially active compounds, which can manifest diverse effects. Expectorant or antitussive effects, which can be accompanied by others, such as anti-inflammatory or antibacterial, are probably the most important in the treatment of coughs. The aim of this review is to summarize the current state of knowledge of the effects of medicinal plants or their constituents on cough, based on reliable pharmacological studies. First, a comprehensive description of each effect is provided in order to explain the possible mechanism of action in detail. Next, the results related to individual plants and substances are summarized and critically discussed based on pharmacological in vivo and in vitro investigation.
- Klíčová slova
- Anti-inflammatory, Antibacterial, Antitussive, Antiviral, Cough, Expectorant, Herbal drugs, Mechanism of action, Medicinal plants, Phytotherapy,
- MeSH
- antitusika * farmakologie MeSH
- expektorancia farmakologie MeSH
- fytoterapie MeSH
- kašel farmakoterapie MeSH
- léčivé rostliny * MeSH
- lidé MeSH
- rostlinné extrakty farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- antitusika * MeSH
- expektorancia MeSH
- rostlinné extrakty MeSH
Cobalt intoxication can occur after its release from metal-based prostheses, which is generally clinically severe. Therefore, there is a need for the development of a cobalt chelator since there are currently no approved drugs for cobalt intoxication. As flavonoids are known for their metal chelating properties and safety, the screening of cobalt chelating properties was performed in a total of 23 flavonoids by our recently developed new spectrophotometric assay. Further assessment of positive or negative consequences of cobalt chelation was performed both in vitro and ex vivo. Six and thirteen flavonoids significantly chelated cobalt ions at pH 7.5 and 6.8, respectively. Baicalein demonstrated a significant activity even at pH 5.5; however, none of the flavonoids showed chelation at pH 4.5. In general, baicalein and 3-hydroxyflavone were the most active. They also mildly decreased the cobalt-triggered Fenton reaction, but baicalein toxicity toward red blood cells was strongly increased by the addition of cobalt. Quercetin, tested as an example of flavonoid unable to chelate cobalt ions significantly, stimulated both the cobalt-based Fenton reaction and the lysis of erythrocytes in the presence of cobalt. Therefore, 3-hydroxyflavone can serve as a potential template for the development of novel cobalt chelators.
- Publikační typ
- časopisecké články MeSH
Flavonoids are common plant natural products able to suppress ROS-related damage and alleviate oxidative stress. One of key mechanisms, involved in this phenomenon is chelation of transition metal ions. From a physiological perspective, iron is the most significant transition metal, because of its abundance in living organisms and ubiquitous involvement in redox processes. The chemical, pharmaceutical, and biological properties of flavonoids can be significantly affected by their interaction with transition metal ions, mainly iron. In this review, we explain the interaction of various flavonoid structures with Fe(II) and Fe(III) ions and critically discuss the influence of chelated ions on the flavonoid biochemical properties. In addition, specific biological effects of their iron metallocomplexes, such as the inhibition of iron-containing enzymes, have been included in this review.
- Klíčová slova
- flavonoids, iron ions, metallocomplexes,
- MeSH
- antioxidancia chemie farmakologie MeSH
- chelátory chemie farmakologie MeSH
- flavonoidy chemie MeSH
- hem chemie MeSH
- ionty chemie metabolismus MeSH
- komplexní sloučeniny chemie MeSH
- lidé MeSH
- molekulární struktura MeSH
- vazba proteinů MeSH
- vztahy mezi strukturou a aktivitou MeSH
- železo chemie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antioxidancia MeSH
- chelátory MeSH
- flavonoidy MeSH
- hem MeSH
- ionty MeSH
- komplexní sloučeniny MeSH
- železo MeSH
Interaction of flavonoids with transition metals can be partially responsible for their impact on humans. Stoichiometry of the iron/copper complex with a flavonoid glycoside isoquercitrin, a frequent component of food supplements, was assessed using competitive and non-competitive methods in four (patho)physiologically-relevant pH values (4.5. 5.5, 6.8, and 7.5). Isoquercitrin chelated all tested ions (Fe2+, Fe3+, Cu2+, and Cu⁺) but its affinity for Cu⁺ ions proved to be very low. In general, the chelation potency dropped with pH lowering. Metal complexes of 1:1 stoichiometry were mostly formed, however, they were not stable and the stoichiometry changed depending on conditions. Isoquercitrin was able to reduce both Cu2+ and Fe3+ ions at low ratios, but its reducing potential was diminished at higher ratios (isoquercitrin to metal) due to the metal chelation. In conclusion, this study emphasizes the need of using multiple different methods for the assessment of chelation potential in moderately-active metal chelators, like flavonoids.
- Klíčová slova
- Job’s method, chelator, copper, iron, quercetin-3-O-β-glucopyranoside, reduction, stoichiometry,
- MeSH
- chelátory chemie MeSH
- flavonoidy chemie MeSH
- koncentrace vodíkových iontů MeSH
- měď chemie MeSH
- quercetin analogy a deriváty chemie MeSH
- železo chemie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- chelátory MeSH
- flavonoidy MeSH
- isoquercitrin MeSH Prohlížeč
- měď MeSH
- quercetin MeSH
- železo MeSH
OBJECTIVES: Rutin, quercetin-3-O-rutinoside, a natural flavonol glycoside, has shown various in vitro benefits with potential use treating human diseases, especially cardiovascular system disorders. Antioxidant properties are assumed to underlie the majority of these benefits. Yet rutin pro-oxidant properties have been reported as well. Our research group has recently shown aggravating effects on isoprenaline (ISO)-induced cardiotoxicity in Wistar:Han rats after 24 hours. METHODS: This study was designed to examine in more detail the reasons for the negative effects of rutin (11.5 and 46 mg/kg, i.v.) after administration of ISO (100 mg/kg, s.c.) in rats within 2 hours of continuous experiment and in the H9c2 cardiomyoblast-derived cell line. RESULTS: Like our previous findings, rutin did not (11.5 or 46 mg/kg, i.v.) reduce the ISO-induced mortality within 2 hours although the lower dose significantly reduced cardiac troponin T (cTnT) and partly improved the histological findings. In contrast, the higher dose increased the mortality in comparison with solvent (1.26% w/v sodium bicarbonate). This was not caused by any specific haemodynamic disturbances. It appears to be associated with oxidative stress as rutin enhanced intracellular reactive oxygen species formation in vitro and had the tendency to increase it in vivo. CONCLUSIONS: Rutin, likely due to its pro-oxidative effects, can exacerbate catecholamine cardiotoxicity depending on the dose used.
- Klíčová slova
- Catecholamine, Flavonoid, H9c2 cell line, Isoprenaline, Reactive oxygen species, Rutin, Wistar rat,
- MeSH
- buněčné linie MeSH
- dinoprost analogy a deriváty krev MeSH
- elektrokardiografie MeSH
- glutathion krev MeSH
- injekce intravenózní MeSH
- isoprenalin škodlivé účinky MeSH
- Kaplanův-Meierův odhad MeSH
- kardiotoxicita etiologie mortalita MeSH
- myokard patologie MeSH
- potkani Wistar MeSH
- reaktivní formy kyslíku metabolismus MeSH
- rutin aplikace a dávkování škodlivé účinky farmakokinetika MeSH
- srdce účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 8-epi-prostaglandin F2alpha MeSH Prohlížeč
- dinoprost MeSH
- glutathion MeSH
- isoprenalin MeSH
- reaktivní formy kyslíku MeSH
- rutin MeSH
Iron and copper release participates in the myocardial injury under ischemic conditions and hence protection might be achieved by iron chelators. Data on copper chelation are, however, sparse. The effect of the clinically used copper chelator D-penicillamine in the catecholamine model of acute myocardial injury was tested in cardiomyoblast cell line H9c2 and in Wistar Han rats. D-Penicillamine had a protective effect against catecholamine-induced injury both in vitro and in vivo. It protected H9c2 cells against the catecholamine-induced viability loss in a dose-dependent manner. In animals, both intravenous D-penicillamine doses of 11 (low) and 44 mg/kg (high) decreased the mortality caused by s.c. isoprenaline (100 mg/kg) from 36% to 14% and 22%, respectively. However, whereas the low D-penicillamine dose decreased the release of cardiac troponin T (specific marker of myocardial injury), the high dose resulted in an increase. Interestingly, the high dose led to a marked elevation in plasma vitamin C. This might be related to potentiation of oxidative stress, as suggested by additional in vitro experiments with D-penicillamine (iron reduction and the Fenton reaction). In conclusion, D-penicillamine has protective potential against catecholamine-induced cardiotoxicity; however the optimal dose selection seems to be crucial for further application.
- MeSH
- buněčné linie MeSH
- chelátory železa farmakologie MeSH
- deferoxamin farmakologie MeSH
- ionty MeSH
- kardiotonika chemie farmakologie MeSH
- katecholaminy MeSH
- koncentrace vodíkových iontů MeSH
- myokard patologie MeSH
- penicilamin chemie farmakologie MeSH
- potkani Wistar MeSH
- troponin T metabolismus MeSH
- viabilita buněk účinky léků MeSH
- železo metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- chelátory železa MeSH
- deferoxamin MeSH
- ionty MeSH
- kardiotonika MeSH
- katecholaminy MeSH
- penicilamin MeSH
- troponin T MeSH
- železo MeSH
OBJECTIVES: This study is an extension to our finding of direct anti-oxidant activities of lanthanide(III) complexes with the heterocyclic compound, 5-aminoorotic acid (AOA). In this experiment, we used AOA and coumarin-3-carboxylic acid as the two heterocyclic compounds with anti-oxidant potential, to produce the complexes with different lanthanides. METHODS: Lanthanide(III) complexes were tested on the iron-driven Fenton reaction. The product of this reaction, the hydroxyl radical, was detected by HPLC. RESULTS: All complexes as well as their ligands had positive or neutral effect on the Fenton reaction but their behavior was different. Both pure ligands in low concentration ratio to iron were inefficient in contrast to some of their complexes. Complexes of neodymium, samarium, gadolinium, and partly of cerium blocked the Fenton reaction at very low ratios (in relation to iron) but the effect disappeared at higher ratios. In contrast, lanthanum complexes appeared to be the most promising. Both blocked the Fenton reaction in a dose-dependent manner. CONCLUSION: Lanthanide(III) complexes were proven to block the iron-driven production of the hydroxyl radical. Second, the lanthanide(III) element appears to be crucial for the anti-oxidant effect. Overall, lanthanum complexes may be promising direct anti-oxidants for future testing.
- Klíčová slova
- 5-Aminoorotic acid, Anti-oxidant, Coumarin-3-carboxylic acid, Iron, Lanthanide(III),
- MeSH
- antioxidancia MeSH
- kumariny chemie MeSH
- kyselina orotová analogy a deriváty chemie MeSH
- lanthanoidy chemie MeSH
- ligandy MeSH
- peroxid vodíku chemie MeSH
- železo chemie MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 5-aminoorotic acid MeSH Prohlížeč
- antioxidancia MeSH
- coumarin-3-carboxylic acid MeSH Prohlížeč
- Fenton's reagent MeSH Prohlížeč
- kumariny MeSH
- kyselina orotová MeSH
- lanthanoidy MeSH
- ligandy MeSH
- peroxid vodíku MeSH
- železo MeSH
Isoflavones are commonly consumed in many Asian countries and have potentially positive effects on human being. Only a few and rather controversial data on their interactions with copper and iron are available to date. 13 structurally related isoflavones were tested in the competitive manner for their Cu/Fe-chelating/reducing properties. Notwithstanding the 5-hydroxy-4-keto chelation site was associated with ferric, ferrous, and cupric chelation, the chelation potential of isoflavones was low and no cuprous chelation was observed. None of isoflavones was able to substantially reduce ferric ions, but the vast majority reduced cupric ions. The most important feature for cupric reduction was the presence of an unsubstituted 4'-hydroxyl; contrarily the presence of a free 5-hydroxyl decreased or abolished the reduction due to chelation of cupric ions. The results from this study may enable additional experiments which might clarify the effects of isoflavones on human being and/or mechanisms of copper absorption.
- MeSH
- isoflavony metabolismus MeSH
- lidé MeSH
- měď metabolismus MeSH
- techniky in vitro MeSH
- železo metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- isoflavony MeSH
- měď MeSH
- železo MeSH