Skin is the largest organ in the human body, and which protects organism against unfavorable external factors e.g., chemicals, environment pollutants, allergens, microorganisms, and it plays a ...crucial role in maintaining general homeostasis. It is also an important target of oxidative stress due to the activity of oxygen reactive species (ROS), which are constantly generated in the fibroblasts in response to exogenous or endogenous prooxidant agents. An example of such compound with proved prooxidant activity is Doxorubicin (DOX), which is an effective anticancer agent belongs in anthracycline antibiotic group. Increasingly frequent implementation of various strategies to reduce undesirable DOX side effects was observed. Very promising results come from the combination of DOX with dietary antioxidants from the polyphenol group of compounds, such as cichoric acid (CA) in order to lower oxidative stress level. The aim of this work was to evaluate the influence of CA combined with DOX on the oxidative stress parameters in fibroblasts, which constitute the main cells in human skin. We also wanted to examine anti-apoptotic activity of CA in fibroblasts treated with selected concentrations of DOX. Results obtained from the combination of DOX with CA revealed that CA exhibits cytoprotective activity against DOX-induced damage by lowering oxidative stress level and by inhibiting apoptosis. The present finding may indicate that CA may serve as antioxidative and anti-apoptotic agent, active against DOX-induced damage.
Apples are among the most popular fruits in the world. They are rich in phenolic compounds, pectin, sugar, macro- and microelements. Applying different extraction techniques it is possible to isolate ...a particular group of compounds or individual chemicals and then test their biological properties. Many reports point to the antioxidant, antimicrobial, anticancer and many other beneficial effects of apple components that may have potential applications in food, pharmaceutical and cosmetic industries. This paper summarizes and compiles information about apple phenolic compounds, their biological properties with particular emphasis on health-related aspects. The data are reviewed with regard to different apple varieties, part of apple, cultivation model and methods of extraction.
Display omitted
•Content of individual phenolic compounds strongly depends on apple variety.•Phenolic compounds act as modulators of signaling pathway in the body.•Chemopreventive properties of apple extracts are well documented.
Since the last few years, the growing interest in the use of natural and synthetic antioxidants as functional food ingredients and dietary supplements, is observed. The imbalance between the number ...of antioxidants and free radicals is the cause of oxidative damages of proteins, lipids, and DNA. The aim of the study was the review of recent developments in antioxidants. One of the crucial issues in food technology, medicine, and biotechnology is the excess free radicals reduction to obtain healthy food. The major problem is receiving more effective antioxidants. The study aimed to analyze the properties of efficient antioxidants and a better understanding of the molecular mechanism of antioxidant processes. Our researches and sparing literature data prove that the ligand antioxidant properties complexed by selected metals may significantly affect the free radical neutralization. According to our preliminary observation, this efficiency is improved mainly by the metals of high ion potential, e.g., Fe(III), Cr(III), Ln(III), Y(III). The complexes of delocalized electronic charge are better antioxidants. Experimental literature results of antioxidant assays, such as diphenylpicrylhydrazyl (DPPH) and ferric reducing activity power assay (FRAP), were compared to thermodynamic parameters obtained with computational methods. The mechanisms of free radicals creation were described based on the experimental literature data. Changes in HOMO energy distribution in phenolic acids with an increasing number of hydroxyl groups were observed. The antioxidant properties of flavonoids are strongly dependent on the hydroxyl group position and the catechol moiety. The number of methoxy groups in the phenolic acid molecules influences antioxidant activity. The use of synchrotron techniques in the antioxidants electronic structure analysis was proposed.
5-O-Caffeoylquinic acid (5-CQA, chlorogenic acid) is one of the major chlorogenic acids present in many fruits, vegetables and herbs. Because of its high biological importance and the widespread ...confusion in the literature concerning the nomenclature of caffeoylquinic acids, the comprehensive structural, spectroscopic and biological studies are necessary. In this work the FT-IR, FT-IR ATR, FT-Raman, UV, 1H (400.15 MHz), 13C (100.63 MHz) and 2D (COSY, HSQC, HMBC) NMR, as well as theoretical (at B3LYP/6-311++G(d,p) level) studies of 5-O-caffeoylquinic acid were carried out. Accurate geometrical parameters as well as atomic charges are reported. Full and proper assignments of bands on vibrational as well as 1H and 13C NMR spectra are made. In addition, 5-CQA was tested for its minimum inhibitory concentration (MIC) against Escherichia coli, Staphylococcus aureus, Enterococcus faecium, Proteus vulgaris, Pseudomonas aeruginosa, Klebsiella pneumoniae and Candida albicans. The obtained MIC values were in the range 5–10 mg/ml. Out of the tested microorganisms, 5-CQA possesses the strongest antimicrobial activity against Klebsiella pneumonia.
•Correct assignment of bands on the 1H and 13C NMR spectra of 5-CQA is reported.•Analysis of the vibrational spectra supported by high-level calculations is done.•The MIC values against the selected bacteria and fungus is found to be 5–10 mg/ml.
Doxorubicin (DOX) is very effective chemotherapeutic agent, however it has several major drawbacks. Therefore the motivation for developing novel drug complexes as anticancer agents with different ...mechanism of action has arisen. The aim of the present study was to evaluate the influence of newly synthesized DOX complexes with selected metals (Mg, Mn, Co, Ni, Fe, Cu, Zn) on apoptosis, cell cycle, viability, proliferation and cytotoxicity in the breast cancer cell line MCF-7. Complexation of DOX with metals has likewise been the subject of our research. The current work showed that the tested bivalent metals at a given pH condition formed metal:DOX complexes in a ratio of 2:1, while iron complexes with DOX in a ratio of 3:1. The studies also showed that selected metal-DOX complexes (Mg-DOX, Mn-DOX, Ni-DOX) at 0.5 µM concentration significantly decreased cell viability and proliferation, however they increased caspase 7 activity. Results also indicated that studied metal-DOX complexes showed high cytotoxicity in MCF-7 cells. Therefore they were chosen for cell cycle check-points and apoptosis/necrosis analysis studied by flow cytometry. Obtained results suggest that doxorubicin complexed by specified metals can be considered as a potential anti-breast cancer agent, which is characterized by a higher efficacy than a parent drug.
The cytoprotective and anticancer action of dietary in-taken natural polyphenols has for long been attributed only to their direct radical scavenging activities. Currently it is well supported that ...those compounds display a broad spectrum of biological and pharmacological outcomes mediated by their complex metabolism, interaction with gut microbiota as well as direct interactions of their metabolites with key cellular signaling proteins. The beneficial effects of natural polyphenols and their synthetic derivatives are extensively studied in context of cancer prophylaxis and therapy. Herein we focus on cell signaling to explain the beneficial role of polyphenols at the three stages of cancer development: we review the recent proceedings about the impact of polyphenols on the cytoprotective antioxidant response and their proapoptotic action at the premalignant stage, and finally we present data showing how phenolic acids (e.g., caffeic, chlorogenic acids) and flavonols (e.g., quercetin) hamper the development of metastatic cancer.
Display omitted
The molecular structure of alkali metal rosmarinates was studied in comparison to rosmarinic acid using FT-IR, FT-Raman,
H and
C NMR spectroscopy, as well as density functional theory (DFT) ...calculations. The B3LYP/6-311+G(d,p) method was used to calculate optimized geometrical structures of studied compounds, atomic charges, dipole moments, energies, as well as the wavenumbers and intensities of the bands in vibrational and NMR spectra. Theoretical parameters were compared to experimental data. Antioxidant activity was determined using two spectrophotometric methods: (i) Assessing the ability to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) stable radical and (ii) assay of antioxidant power of ferric ions reducing (FRAP). The linear correlations were found between HOMO-LUMO (highest occupied molecular orbital-lowest unoccupied molecular orbital) energy gap and the reducing power expressed as FRAP (R = 0.77) as well as between IC
values (the ability of quenching DPPH radicals) and
(COO) in IR spectra (differences between asymmetric and symmetric stretching vibrations bands) (R = 0.99). Photochemical properties of studied compounds were also evaluated. The influence of alkali metal on the electronic system of the rosmarinic acid molecule was discussed.
Anthracyclines currently play a key role in the treatment of many cancers, but the limiting factor of their use is the widespread phenomenon of drug resistance and untargeted toxicity. Flavonoids ...have pleiotropic, beneficial effects on human health that, apart from antioxidant activity, are currently considered small molecules-starting structures for drug development and enhancers of conventional therapeutics. This paper is a review of the current and most important data on the participation of a selected series of flavonoids: chrysin, apigenin, kaempferol, quercetin and myricetin, which differ in the presence of an additional hydroxyl group, in the formation of a synergistic effect with anthracycline antibiotics. The review includes a characterization of the mechanism of action of flavonoids, as well as insight into the physicochemical parameters determining their bioavailability in vitro. The crosstalk between flavonoids and the molecular activity of anthracyclines discussed in the article covers the most important common areas of action, such as (1) disruption of DNA integrity (genotoxic effect), (2) modulation of antioxidant response pathways, and (3) inhibition of the activity of membrane proteins responsible for the active transport of drugs and xenobiotics. The increase in knowledge about the relationship between the molecular structure of flavonoids and their biological effect makes it possible to more effectively search for derivatives with a synergistic effect with anthracyclines and to develop better therapeutic strategies in the treatment of cancer.
The research was conducted in the "logical series" of seven ligands: chromone, flavone, 3-hydroxyflavone, 3,7-dihydroxyflavone, galangin, kaempferol and quercetin. Each subsequent ligand differs from ...the previous one, among others by an additional hydroxyl group. The studied chromone derivatives are plant secondary metabolites which play an important role in growth, reproduction, and resistance to pathogens. They are important food ingredients with valuable pro-health properties. The studies of the relationships between their molecular structure and biological activity facilitate searching for new chemical compounds with important biological properties not by trial and error, but concerning the impact of specific changes in their structure on the compound properties. Therefore several pectroscopic methods (FT-IR, FT-Raman, .sup.1 H and .sup.13 C NMR) were applied to study the molecular structure of the compounds in the series. Moreover the quantum-chemical calculations at B3LYP/6-311++G** were performed to obtained the theoretical NMR spectra, NBO atomic charge, global reactivity descriptors and thermodynamic parameters. The antioxidant activity of the compounds was tested in the DPPH and FRAP assays and the mechanism of antioxidant activity was discussed based on the results on theoretical calculations. The cytotoxicity of the ligands toward human epithelial colorectal adenocarcinoma Caco2 cells was estimated and correlated with the lipophilicity of the compounds. The principal component analyses (PCA) and hierarchical cluster analysis were used to study the dependency between the molecular structure of ligands and their biological activity. The experimental data were related to the theoretical ones. The found regular changes in physicochemical properties correlated well with the systematic changes in antioxidant and biological properties.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The structure of the Zn(II) complex of 5-caffeoylquinic acid (chlorogenic acid, 5-CQA) and the type of interaction between the Zn(II) cation and the ligand were studied by means of various ...experimental and theoretical methods, i.e., electronic absorption spectroscopy UV/Vis, infrared spectroscopy FT-IR, elemental, thermogravimetric and density functional theory (DFT) calculations at B3LYP/6-31G(d) level. DPPH (2,2-diphenyl-1-picrylhydrazyl), ABTS (2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), FRAP (ferric reducing antioxidant power), CUPRAC (cupric reducing antioxidant power) and trolox oxidation assays were applied in study of the anti-/pro-oxidant properties of Zn(II) 5-CQA and 5-CQA. The antimicrobial activity of these compounds against Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus, Salmonella enteritidis and Candida albicans was tested. An effect of Zn(II) chelation by chlorogenic acid on the anti-/pro-oxidant and antimicrobial activities of the ligand was discussed. Moreover, the mechanism of the antioxidant properties of Zn(II) 5-CQA and 5-CQA were studied on the basis of the theoretical energy descriptors and thermochemical parameters. Zn(II) chlorogenate showed better antioxidant activity than chlorogenic acid and commonly applied natural (L-ascorbic acid) and synthetic antioxidants (butylated hydroxyanisol (BHA) and butylated hydroxytoluene (BHT)). The pro-oxidant activity of Zn(II) 5-CQA was higher than the ligand and increased with the rise of the compound concentration The type of Zn(II) coordination by the chlorogenate ligand strongly affected the antioxidant activity of the complex.
PDF
