ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease is the most common form of dementia, but its treatment options remain few and ineffective. To find new therapeutic strategies, natural products have gained interest due to their neuroprotective potential, being able to target different pathological hallmarks associated with this disorder. Several plant species are traditionally used due to their empirical neuroprotective effects and it is worth to explore their mechanism of action. AIM OF THE STUDY: This study intended to explore the neuroprotective potential of seven traditional medicinal plants, namely Scutellaria baicalensis, Ginkgo biloba, Hypericum perforatum, Curcuma longa, Lavandula angustifolia, Trigonella foenum-graecum and Rosmarinus officinalis. The safety assessment with reference to pesticides residues was also aimed. MATERIALS AND METHODS: Decoctions prepared from these species were chemically characterized by HPLC-DAD and screened for their ability to scavenge four different free radicals (DPPH•, ABTS•+, O2•‒ and •NO) and to inhibit enzymes related to neurodegeneration (cholinesterases and glycogen synthase kinase-3β). Cell viability through MTT assay was also evaluated in two different brain cell lines, namely non-tumorigenic D3 human brain endothelial cells (hCMEC/D3) and NSC-34 motor neurons. Furthermore, and using GC, 21 pesticides residues were screened. RESULTS: Regarding chemical composition, chromatographic analysis revealed the presence of several flavonoids, phenolic acids, curcuminoids, phenolic diterpenoids, one alkaloid and one naphthodianthrone in the seven decoctions. All extracts were able to scavenge free radicals and were moderate glycogen synthase kinase-3β inhibitors; however, they displayed weak to moderate acetylcholinesterase and butyrylcholinesterase inhibition. G. biloba and L. angustifolia decoctions were the less cytotoxic to hCMEC/D3 and NSC-34 cell lines. No pesticides residues were detected. CONCLUSIONS: The results extend the knowledge on the potential use of plant extracts to combat multifactorial disorders, giving new insights into therapeutic avenues for Alzheimer's disease.
- MeSH
- Alzheimerova nemoc patologie MeSH
- buněčné linie MeSH
- cholinesterasy účinky léků MeSH
- glykogensynthasa účinky léků MeSH
- léčivé rostliny chemie MeSH
- lidé MeSH
- neuroprotektivní látky škodlivé účinky farmakologie MeSH
- rezidua pesticidů analýza MeSH
- rostlinné extrakty škodlivé účinky farmakologie MeSH
- scavengery volných radikálů metabolismus MeSH
- tradiční čínská medicína metody MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Quercetin, a common flavonoid from human diet, is extensively metabolized. Its two metabolites with the preserved flavonoid core were tested in detail for their interactions with transition metals, iron and copper. Both compounds chelated both metals; however, there were some significant differences between them notwithstanding that the major chelation site (3-hydroxy-4-keto) was the same. The complex stoichiometries were also determined under different pH conditions and in both oxidation states. Mostly, complexes 2:1, flavonoid to metal, were observed. Both compounds reduced iron and copper in a bell-shaped manner with tamarixetin being less potent in general. Both metabolites potentiated the Fenton reaction triggered by iron, while they were able to decrease the copper-based Fenton reaction under acidic conditions. In cellular experiments, both metabolites attenuated the copper-triggered hemolysis with isorhamnetin being more potent. In conclusion, there are differences between methylated metabolites of quercetin in relation to their interactions with biologically relevant transition metals.
- MeSH
- disacharidy MeSH
- lidé MeSH
- měď * MeSH
- quercetin * analogy a deriváty MeSH
- železo MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Some compounds without apparent chelation sites have been shown to chelate cupric ions using the hematoxylin assay. Since these compounds also have reduction potential (direct antioxidant effect), the aim of this study was to determine the possible interference of reducing agents with the hematoxylin assay. Four different known reducing agents (hydroxylamine, vitamin C, trolox - a water-soluble form of vitamin E and reduced glutathione /GSH/) were selected for the study together with oxidized glutathione (GSSG) for comparison. All tested compounds behaved as cupric chelators in the spectrophotometric mildly competitive hematoxylin assay. In-depth analysis however showed that only GSH and GSSG were able to form complexes with both cupric and cuprous ions and only GSSG partly retained copper in its complexes in the more competitive bathocuproine assay. Further experiments showed that with the exception of GSSG, all other compounds reduce Cu2+ ions. Conclusion: Compounds reducing copper such as antioxidants can give false positive results in the hematoxylin-screening assay. GSSG is a stronger Cu chelator than GSH and does not reduce Cu, in contrast to the latter and thus may be a protective element after oxidation of GSH.
- MeSH
- chelátory chemie MeSH
- falešně pozitivní reakce * MeSH
- hematoxylin chemie MeSH
- měď chemie MeSH
- molekulární konformace MeSH
- Publikační typ
- časopisecké články MeSH
SCOPE: Intake of flavonoids from the diet can be substantial, and epidemiological studies suggest that these compounds can decrease the incidence of cardiovascular diseases by involvement with increased platelet aggregation. Although parent flavonoids possess antiplatelet effects, the clinical importance is disputable due to their very low bioavailability. Most of them are metabolized by human colon bacteria to smaller phenolic compounds, which reach higher plasma concentrations than the parent flavonoids. In this study, a series of 29 known flavonoid metabolites is tested for antiplatelet potential. METHODS AND RESULTS: Four compounds appear to have a biologically relevant antiplatelet effect using whole human blood. 4-Methylcatechol (4-MC) is clearly the most efficient being about 10× times more active than clinically used acetylsalicylic acid. This ex vivo effect is also confirmed using a potentially novel in-vivo-like ex ovo hen's egg model of thrombosis, where 4-MC significantly increases the survival of the eggs. The mechanism of action is studied and it seems that it is mainly based on the influence on intracellular calcium signaling. CONCLUSION: This study shows that some flavonoid metabolites formed by human microflora have a strong antiplatelet effect. This information can help to explain the antiplatelet potential of orally given flavonoids.
- MeSH
- agregace trombocytů účinky léků MeSH
- inhibitory agregace trombocytů farmakologie MeSH
- inhibitory cyklooxygenasy farmakologie MeSH
- inhibitory enzymů farmakologie MeSH
- katecholy farmakologie MeSH
- kuřecí embryo MeSH
- kyselina arachidonová farmakologie MeSH
- lidé MeSH
- preklinické hodnocení léčiv metody MeSH
- pyrogalol farmakologie MeSH
- serotonin metabolismus MeSH
- thromboxan-A synthasa antagonisté a inhibitory MeSH
- trombóza farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- kuřecí embryo MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
