Anti-osteoporosis effect of bioactives in edible medicinal plants: a comprehensive review.

Current treatments for osteoporosis include a calcium-rich diet, adequate exercise, and medication. Many synthetic drugs, although fast-acting, can cause a range of side effects for patients when taken over a long period, such as irritation of the digestive tract and a burden on the kidneys. As the world's population ages, the prevalence of osteoporosis is increasing, and the development of safe and effective treatments is urgently needed. Active compounds in edible and medicinal homologous plants have been used for centuries to improve bone quality. It is possible to employ them as dietary supplements to prevent osteoporosis. In this review, we analyze the influencing factors of osteoporosis and systematically summarize the research progress on the anti-osteoporosis effects of active compounds in edible and medicinal homologous plants. The literature suggests that some naturally occurring active compounds in edible and medicinal homologous plants can inhibit bone loss, prevent the degeneration of bone cell microstructure, and reduce bone fragility through alleviating oxidative stress, regulating autophagy, anti-inflammation, improving gut flora, and regulating estrogen level with little side effects. Our review provides useful guidance for the use of edible and medicinal homologous plants and the development of safer novel anti-osteoporosis dietary supplements.

The Influence of Mesotrione on Human Colorectal Adenocarcinoma Cells and Possibility of Its Toxicity Mitigation by Cichoric Acid.

Mesotrione, as a widely used herbicide, is present in the environment in detectable amounts, causing serious damage. Here, we aimed to investigate the effect of mesotrione on Caco-2 cells and the possibility of its toxicity mitigation by cichoric acid. Therefore, we analyzed the cytotoxicity of both these compounds and the selected oxidative stress parameters, apoptosis and interaction of both the tested compounds with the cell membrane and their accumulation within the cells. In cytotoxicity studies, the stimulating activity of mesotrione was observed, and simultaneously, the inhibitory effect of cichoric acid was noticed. This effect was related to the results of oxidative stress analysis and apoptosis measurements. The activity level of key enzymes (glutathione peroxidase, catalase and superoxide dismutase) in Caco-2 cells exposed to cichoric acid was higher as compared to that of the control. The treatment with mesotrione did not induce apoptosis in the Caco-2 cells. The penetration of the studied compounds into the Caco-2 cells was measured by using an HPLC methodology, and the results indicate mesotrione's high penetration capacity. The distribution of charge on the surface of the cell membranes changed under the influence of both compounds. Considering the mutual interactions of beneficial and potentially toxic food ingredients, it should be noted that, despite the observed favorable trend, cichoric acid is not able to overcome the toxic and cancer-stimulating effects of this pesticide.

Metal-Flavonoid Interactions-From Simple Complexes to Advanced Systems.

For many years, metal-flavonoid complexes have been widely studied as a part of drug discovery programs, but in the last decade their importance in materials science has increased significantly. A deeper understanding of the role of metal ions and flavonoids in constructing simple complexes and more advanced hybrid networks will facilitate the assembly of materials with tailored architecture and functionality. In this Review, we highlight the most essential data on metal-flavonoid systems, presenting a promising alternative in the design of hybrid inorganic-organic materials. We focus mainly on systems containing CuII/I and FeIII/II ions, which are necessary in natural and industrial catalysis. We discuss two kinds of interactions that typically ensure the formation of metal-flavonoid systems, namely coordination and redox reactions. Our intention is to cover the fundamentals of metal-flavonoid systems to show how this knowledge has been already transferred from small molecules to complex materials.

Structures, Antioxidant Properties, and Antimicrobial Properties of Eu(III), Gd(III), and Dy(III) Caffeinates and p-Coumarates.

In this study, we investigated the structures of lanthanide (Eu(III), Dy(III), and Gd(III)) complexes with p-coumaric (p-CAH2) and caffeic (CFAH3) acids using the FTIRKBr, FTIRATR, and Raman spectroscopic methods. The compositions of the solid phase caffeinates and p-coumarates were obtained on the basis of the amounts of hydrogen and carbon determined using an elemental analysis. The degree of hydration and the thermal decomposition of each compound were examined via a thermal analysis of TG, DTG, and DSC. Antioxidant spectroscopic tests were performed using the DPPH (1,1-diphenyl-2-picrylhydrazyl radical), FRAP (ferric reducing antioxidant activity), and ABTS (2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (diammonium salt radical cation) methods. The antimicrobial activity of each compound against Escherichia coli, Bacillus subtilis, and Candida albicans was investigated. The electrical properties of the liposomes which mimicked the microbial surfaces formed in the electrolyte containing the tested compounds were also investigated. The above biological properties of the obtained complexes were compared with the activities of p-CAH2 and CFAH3. The obtained data suggest that lanthanide complexes are much more thermally stable and have higher antimicrobial and antioxidant properties than the ligands (with the exception of CFAH3 in the case of antioxidant activity tests). The Gd(III) complexes revealed the highest biological activity among the studied lanthanide complexes.

Caffeic Acid/Eu(III) Complexes: Solution Equilibrium Studies, Structure Characterization and Biological Activity.

Caffeic acid (CFA) is one of the various natural antioxidants and chemoprotective agents occurring in the human diet. In addition, its metal complexes play fundamental roles in biological systems. Nevertheless, research on the properties of CFA with lanthanide metals is very scarce, and little to no chemical or biological information is known about these particular systems. Most of their properties, including their biological activity and environmental impact, strictly depend on their structure, stability, and solution behaviour. In this work, a multi-analytical-technique approach was used to study these relationships for the Eu(III)/CFA complex. The synthesized metal complex was studied by FT-IR, FT-Raman, elemental, and thermal (TGA) analysis. In order to examine the chemical speciation of the Eu(III)/CFA system in an aqueous solution, several independent potentiometric and spectrophotometric UV-Vis titrations were performed at different M:L (metal:ligand) and pH ratios. The general molecular formula of the synthesized metal complex in the solid state was [Eu(CFA)3(H2O)3]∙2H2O (M:L ratio 1:3), while in aqueous solution the 1:1 species were observed at the optimum pH of 6 ≤ pH ≤ 10, ([Eu(CFA)] and [Eu(CFA)(OH)]-). These results were confirmed by 1H-NMR experiments and electrospray-ionization mass spectrometry (ESI-MS). To evaluate the interaction of Eu(III)/CFA and CFA alone with cell membranes, electrophoretic mobility assays were used. Various antioxidant tests have shown that Eu(III)/CFA exhibits lower antioxidant activity than the free CFA ligand. In addition, the antimicrobial properties of Eu(III)/CFA and CFA against Escherichia coli, Bacillus subtilis and Candida albicans were investigated by evaluation of the minimum inhibitory concentration (MIC). Eu(III)/CFA shows higher antibacterial activity against bacteria compared to CFA, which can be explained by the highly probable increased lipophilicity of the Eu(III) complex.

Vulvar cancer in a patient with long-lasting premalignant lesions in the genital area: easily overlooked and difficult to diagnose - a case report and literature review.

Vulvar intraepithelial lesions are a heterogenic group of diseases, which can be easily misdiagnosed. The case of a 61-year-old woman with a history of genital intraepithelial lesions and infection with HPV is presented. Her main complaint was vulvar pruritus. Vulvoscopy revealed the presence of two skin lesions: the first one had the morphology of lichen sclerosus, and the second of a Bowenoid lesion. The biopsy of the first lesion revealed vulvar intraepithelial neoplasia, whereas cells of squamous vulvar cancer were identified in the second lesion. After staging, the patient was advised to undergo hemivulvectomy and lymphadenectomy. The coexistence of morphologically diverse vulvar skin lesions may cause difficulties with diagnosis and the selection of an adequate treatment. Long-term follow-up and regular examination are essential for diagnosis of vulvar malignancies in the early stage.

The Study of Anti-/Pro-Oxidant, Lipophilic, Microbial and Spectroscopic Properties of New Alkali Metal Salts of 5-O-Caffeoylquinic Acid.

Lithium, sodium, potassium, rubidium and caesium salts of 5-O-caffeoylquinic acid (chlorogenic acid, 5-CQA) were synthesized and described by FT-IR (infrared spectroscopy), FT-Raman (Raman spectroscopy), UV (UV absorption spectroscopy), ¹H (400.15 MHz), 13C (100.63 MHz) NMR (nuclear magnetic resonance spectroscopy). The quantum-chemical calculations at the B3LYP/6-311++G** level were done in order to obtain the optimal structures, IR spectra, NBO (natural bond orbital) atomic charges, HOMO (highest occupied molecular orbital) and LUMO (lowest unoccupied molecular orbital) orbitals and chemical reactivity parameters for 5-CQA and Li, Na and K 5-CQAs (chlorogenates). The DPPH (α, α-diphenyl-ß-picrylhydrazyl) and FRAP (ferric reducing antioxidant power) assays were used for the preliminary estimation of the antioxidant properties of alkali metal chlorogenates and chlorogenic acid. In the DPPH assay the EC50 parameter were equal to 7.39 µM for 5-CQA and was in the range of 4.50-5.89 µM for salts. The FRAP values for two different concentrations (5 and 2.5 µM) of the studied compounds were respectively 114.22 and 72.53 µM Fe2+ for 5-CQA, whereas for salts they were 106.92-141.13 and 78.93-132.00 µM Fe2+. The 5-CQA and its alkali metal salts possess higher antioxidant properties than commonly applied antioxidants (BHA, BHT, l-ascorbic acid). The pro-oxidant action of these compounds on trolox oxidation was studied in the range of their concentration 0.05-0.35 µM. The lipophilicity (logkw) of chlorogenates and chlorogenic acid was determined by RP-HPLC (reverse phase-high performance liquid chromatography) using five different columns (C8, PHE (phenyl), CN (cyano), C18, IAM (immobilized artificial membrane)). The compounds were screened for their in vitro antibacterial activity against E. coli, Bacillus sp., Staphylococcus sp., Streptococcus pyogenes and antifungal activity against Candida sp. The 5-CQA possessed lower antibacterial (minimal inhibitory concentration, MIC = 7.06 mM) and antifungal (MIC = 14.11 mM) properties than its alkali metal salts (MIC values: 6.46-2.63 mM and 12.91-5.27mM, respectively). The synthesized chlorogenates possessed better antioxidant, lipophilic, antimicrobial as well as lower pro-oxidant properties than the ligand alone. Moreover, a systematic change of the activity of alkali metal salts along the series Li→Cs suggests that there are correlations between the studied biological properties. The type of metal cation in the carboxylate group of chlorogenate is crucial for the activity of studied compounds.

Barriers to cervical cancer screening exist despite integrating HIV and gynaecological services for HIV-positive women in Poland.

OBJECTIVES: HIV-positive women are at increased risk of HPV infection and cervical cancer. European and national guidelines advise yearly screening for cervical cancer, however due to the lack of a central registration of HIV infected persons there is a gap in offering such care through general healthcare services in many countries, including Poland. MATERIAL AND METHODS: In response to the above limitations, integrated gynaecological care (IGC) was established at the HIV Out-Patient Clinic in Warsaw. We analysed data from January 2007 to May 2014. Logistic regression models were used to identify factors associated with not using IGC by patients. RESULTS: Two hundred and forty women were registered in the observation period:59.6% infected through sexual contact, 18.7% through IDUs, 19.2 % through unknown causes and 2.5% by other (two were vertically infected). The median follow-up time was 2.35 (IQR 0.9-4.5) years and 78.3% were on combination antiretroviral therapy (cART). In total 145 of the women (60.4%) used IGC, from 72.1% of those registered in 2007 to 27.3% registered in 2014. There were in total 1075 gynaeco-logical visits and 254 cervical cytology tests performed. Seventy-five (51.7%) women were tested for HPV infection. Fac-tors decreasing the odds of not using IGC identified by multivariate regression models were being on cART (OR 0.25 [IQR: 0.10-0.59]; p = 0.003) and longer time of observation (0.69 [0.58-0.83]; p = 0.0001). CONCLUSIONS: The utilisation of IGC was very high, but with a delay in commencing the IGC. Women on cART and with longer periods of follow-up had lower odds of not using IGC. A screening approach for women not yet on cART, or newly registered in the clinics, needs special attention.

MONITORING OF SYNERGISTIC ENHANCEMENT OF CAFFEIC ACID ON ESCHERICHIA COLI K-12 RECA::GFP STRAIN TREATED WITH DACARBAZINE.

Caffeic acid and its derivatives because of its biological activities, including antioxidants, antithrombosis, antihypertensive, antifibrosis, antiviral, and anti-tumor properties are good candidates as adjuvants in anticancer therapy. The aim of this study was the examination of cyto- and genotoxic effect of caffeic acid on Escherichia coli K-12 recA::gfp strain treated with dacarbazine. Obtained results indicate that dacarbazine and caffeic acid influenced the reactivity of recA promoter and modulate the level of gfp expression in genetic construct rrcA::gfpmut2 in E. coli K-12. Simultaneuos administration of dacarbazine with caffeic acid caused the stronger inhibition of the bacteria growth than the dacarbazine and caffeic acid separated administration to bacteria cells. The simultaneous effect of the both tested chemicals - dacarbazine and caffeic acid indicated (cytostatic effect) anticancer activity in relation to bacteria cells. It suggests, that combination of known anticancer drug - dacarbazine w ith caffeic acid exerted synergistic cytotoxic and genotoxic effects toward E. coli K- 12 cells and indicated the possibility of usefulness of caffeic acid as a natural adjuvant in anticancer therapy.

IN VITRO EVALUATION OF BIOLOGICAL ACTIVITY OF CINNAMIC, CAFFEIC, FERULIC AND CHLOROGENIC ACIDS WITH USE OF ESCHERICHIA COLI K-12 RECA::GFP BIOSENSOR STRAIN.

Cinnamic acid and its derivatives are important and promising compounds in cancer therapy, because of its broad spectrum of anicancer and antioxidative ability, and with high potential for development into new generation drugs. The aim of this study was to compare the cyto- and genotoxic effects of cinnamic acid and its derivatives with the use of4Escherichia coli K-12 recA::gfp microbial biosensor strain with plasmid fusion of recA promoter and gfp gene as reporter. Obtained results indicate that recA::gfpmut2 genetic system was a sensitive biosensor to the most chemicals tested in our experiments. The cinnamic acid and its derivatives modulated the reactivity of wcA promoter in relation to control sample and significantly inhibited bacteria cells growth. In the light of our results only chlorogenic and ferulic acids at higher concentrations demonstrated cyto and genotoxic activity toward to E. coli K-12 mcA::gfp cells.

CYTOTOXIC AND GENOTOXIC STUDIES OF QUERCETIN, QUERCETIN SODIUM SALT AND QUERCETIN COMPLEXES WITH NICKEL (II) AND ZINC (II).

The aim of this study was to compare the cyto- and genotoxic effects of quercetin, quercetin sodium salt as well as its complexes with nickel (II) and zinc (II) with the use of Escheiichia coli K-12 recA::gfp microbial biosensor strain containing transcriptional fusion between DNA-damage genotoxin-inducible recA promoter involved in the SOS regulon response and fast folding GFP (green fluorescent protein) variant reporter gene - gfpnmt2. Obtained results indicate that recA::gfpmut2 genetic system was a sensitive biosensor to the most of tested chemicals. The complex of quercetin with sodium, nickel and zinc increased (and in some cases modulated) the reactivity of ircA promoter in relation to control sample. The results indicated that E. coli K-12 iecA::gfp mut2 strain could be potentially useful for monitoring of cytotoxic and genotoxic effect of some biological natural compounds, potentially used in anticancer chemoprevention and therapy.

Comparison of Physicochemical, Antioxidant, and Cytotoxic Properties of Caffeic Acid Conjugates.

Spectroscopic studies (FT-IR, Raman, 1H, and 13C NMR, UV-VIS) of caffeic acid (CFA) and its conjugates, i.e., caftaric acid (CTA), cichoric acid (CA), and cynarin (CY), were carried out. The antioxidant activity of these compounds was determined by a superoxide dismutase (SOD) activity assay and the hydroxyl radical (HO•) inhibition assay. The cytotoxicity of these compounds was performed on DLD-1 cell lines. The molecules were theoretically modeled using the B3LYP-6-311++G(d,p) method. Aromaticity indexes (HOMA, I6, BAC, Aj), HOMO and LUMO orbital energies and reactivity descriptors, NBO electron charge distribution, EPS electrostatic potential maps, and theoretical IR and NMR spectra were calculated for the optimized model systems. The structural features of these compounds were discussed in terms of their biological activities.

Structural characterization and evaluation of antimicrobial and cytotoxic activity of six plant phenolic acids.

Phenolic acids still gain significant attention due to their potential antimicrobial and cytotoxic properties. In this study, we have investigated the antimicrobial of six phenolic acids, namely chlorogenic, caffeic, p-coumaric, rosmarinic, gallic and tannic acids in the concentration range 0.5-500 µM, against Escherichia coli and Lactobacillus rhamnosus. The antimicrobial activity was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Additionally, the cytotoxic effects of these phenolic acids on two cancer cell lines, the colorectal adenocarcinoma Caco-2 cell line and Dukes' type C colorectal adenocarcinoma DLD-1 cell line was examined. To further understand the molecular properties of these phenolic acids, quantum chemical calculations were performed using the Gaussian 09W program. Parameters such as ionization potential, electron affinity, electronegativity, chemical hardness, chemical softness, dipole moment, and electrophilicity index were obtained. The lipophilicity properties represented by logP parameter was also discussed. This study provides a comprehensive evaluation of the antimicrobial and cytotoxic activity of six phenolic acids, compounds deliberately selected due to their chemical structure. They are derivatives of benzoic or cinnamic acids with the increasing number of hydroxyl groups in the aromatic ring. The integration of experimental and computational methodologies provides a knowledge of the molecular characteristics of bioactive compounds and partial explanation of the relationship between the molecular structure and biological properties. This knowledge aids in guiding the development of bioactive components for use in dietary supplements, functional foods and pharmaceutical drugs.

Structure, Antioxidant Activity and Antimicrobial Study of Light Lanthanide Complexes with p-Coumaric Acid.

This paper presents the results of a study of the effects of the lanthanide ions Ce3+, Pr3+, Nd3+ and Sm3+ on the electronic structure and antioxidant and biological (antimicrobial and cytotoxic) properties of p-coumaric acid (p-CAH2). Structural studies were conducted via spectroscopic methods (FTIR, ATR, UV). Thermal degradation studies of the complexes were performed. The results are presented in the form of TG, DTG and DSC curves. Antioxidant properties were determined via activity tests against DPPH, ABTS and OH radicals. The reducing ability was tested via CUPRAC assays. Minimum inhibitory concentrations (MICs) of the ligand and lanthanide complexes were determined on E. coli, B. subtilis and C. albicans microorganisms. The antimicrobial activity was also determined using the MTT assay. The results were presented as the relative cell viability of C. albicans, P. aeruginosa, E. coli and S. aureus compared to controls and expressed as percentages. In the obtained complexes in the solid phase, lanthanide ions coordinate three ligands in a bidentate chelating coordination mode through the carboxyl group of the acid. Spectroscopic analysis showed that lanthanide ions increase the aromaticity of the pi electron system of the ligand. Thermal analysis showed that the complexes are hydrated and have a higher thermal stability than the ligand. The products of thermal decomposition of the complexes are lanthanide oxides. In the aqueous phase, the metal combines with the ligand in a 1:1 molar ratio. Antioxidant activity tests showed that the complexes have a similar ability to remove free radicals. ABTS and DPPH tests showed that the complexes have twice the ability to neutralise radicals than the ligand, and a much higher ability to remove the hydroxyl radical. The abilities of the complexes and the free ligand to reduce Cu2+ ions in the CUPRAC test are at a similar level. Lanthanide complexes of p-coumaric acid are characterised by a higher antimicrobial capacity than the free ligand against Escherichia coli bacteria, Bacillus subtilis and Candida albicans fungi.

Sustainable extraction of bioactive compound from apple pomace through lactic acid bacteria (LAB) fermentation.

Apple pomace (AP), a by-product of the juice industry, is a rich and inexpensive source of natural bioactive substances, including phenolic compounds, that exhibit health-promoting effects. The recovery of these compounds from plant material using only classical extraction techniques and environmentally friendly solvents is often ineffective due to the entrapment of some compounds in the complex structures of plant cell walls. Lactic Acid Bacteria (LAB) fermentation can be a simple technology to increase the content of phenolic compounds, as well as the antioxidant activity of plant material. In this study, pomace from conventionally grown apples (Malus Domestica) of the Ligol cultivar were fermented with selected LAB strains (Lpb. plantarum KKP 3182, Lpb. plantarum KKP 1527, Lpb. plantarum ZFB 200), commercial starter cultures of Lpb. plantarum, and spontaneously. The fermented material was then subjected to ultrasound-assisted extraction, and the resulting extracts were analysed for their composition (phenolic compounds, triterpenoids, simple organic acids), and antioxidant activity. We found that: (1) the total phenolic content of AP extracts fermented with Lpb. plantarum KKP 1527 was about 30% higher than that of non-fermented AP extracts, (2) extracts of AP fermented with Lpb. plantarum KKP 1527 characterized a higher value of the antioxidant activity, (3) an increase in gallic acid procyanidin A2, protocatechuic acid, and procyanidin B2, while a decrease in rutin and quercetin was observed. The results indicated that AP fermented with Lpb. plantarum KKP 1527 may be a powerful and low-cost source of natural antioxidants which have applications in many industries.

Sustainable Use of Apple Pomace (AP) in Different Industrial Sectors.

In many countries, apple pomace (AP) is one of the most produced types of agri-food waste (globally, it is produced at a rate of ~4 million tons/year). If not managed properly, such bio-organic waste can cause serious pollution of the natural environment and public health hazards, mainly due to the risk of microbial contamination. This review shows that AP can be successfully reused in different industrial sectors-for example, as a source of energy and bio-materials-according to the idea of sustainable development. The recovered active compounds from AP can be applied as preservatives, antioxidants, anti-corrosion agents, wood protectors or biopolymers. Raw or processed forms of AP can also be considered as feedstocks for various bioenergy applications such as the production of intermediate bioenergy carriers (e.g., biogas and pyrolysis oil), and materials (e.g., biochar and activated carbon). In the future, AP and its active ingredients can be of great use due to their non-toxicity, biodegradability and biocompatibility. Given the increasing mass of produced AP, the commercial applications of AP could have a huge economic impact in the future.

Comparing the extraction methods, chemical composition, phenolic contents and antioxidant activity of edible oils from Cannabis sativa and Silybum marianu seeds.

In the study the cold-pressed, natural (unfiltered, unrefined) vegetable oils: hemp and milk thistle seed oils were tested for their chemical composition and antioxidant properties. The physico-chemical parameters, content of saturated and unsaturated fatty acids were determined. Solid phase extraction and simple extraction with the use of methanol, ethanol, 80% methanol, 80% ethanol were used to obtain the extracts for the analysis of antioxidant activity and phenolic compounds in oils. The composition of phenolic compounds was studied by means of high-performance liquid chromatography (HPLC-DAD) and spectrophotometric test with the Folin-Ciocalteu reagent. The antioxidant property of extracts was established by means of the following methods: with the DPPH• (2,2-diphenyl-1-picrylhydrazyl) radical, ABTS•+ (2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) cation radical, FRAP (ferric ion reducing antioxidant parameter) and CUPRAC (cupric-reducing antioxidant capacity). Moreover the influence of chlorogenic acid on the inhibition of lipid peroxidation process in the hemp and milk thistle seed oils was also investigated. The tested oils showed different antioxidant properties which was related to the their different chemical composition. The main phenolic compounds present in hemp seed oil were vanillic, ferulic and p-coumaric acids, (-)epicatechin, catechin, kaempferol and procyanidin B2, whereas in milk thistle seed oil-catechins, procyanidin B2, procyanidin C1, p-coumaric acid, phloridzin, quercetin, protocatechuic acid, kaempferol, and syringic acid. The methanolic extracts of hemp and milk thistle seed oils showed the highest antiradical activity, whereas the ethanolic extracts revealed the best reducing properties. The obtained antioxidant parameters for hemp seed oil were: the IC50 = 3.433 ± 0.017 v/v (DPPH test), the percent of ABTS•+ inhibition = 93.301 ± 1.099%, FRAP value = 1063.883 ± 39.225 µmol Fe2+, CUPRAC value = 420.471 ± 1.765 µmol of Trolox. Whereas the antioxidant parameters for milk thistle seed oil were: the IC50 = 5.280 ± 0.584 v/v (DPPH test), 79.59 ± 3.763% (ABTS test), 2891.08 ± 270.044 µmol Fe2+ (FRAP test), 255.48 ± 26.169 µmol of Trolox (CUPRAC assay). Chlorogenic acid effectively inhibited the lipid peroxidation process in hemp and milk thistle seed oils.

Fe(III) and Cu(II) Complexes of Chlorogenic Acid: Spectroscopic, Thermal, Anti-/Pro-Oxidant, and Cytotoxic Studies.

Complexes of chlorogenic acid (5-CQA) with copper(II) and iron(III) were synthesized in a solid state and examined by means of FT-IR, thermogravimetric, and elemental analyses. The molar stoichiometric ratios of metal:ligand for the solid forms of the complexes were established as Cu(II):L = 1:2 and Fe(III):L = 2:3 (L: 5-CQA), with the possible coordination through the carboxylate group and the hydroxyl group from the catechol moiety. In an aqueous solution at pH = 7.4, the composition of the complexes was Cu(II):L = 1:1, and Fe(III):L = 1:1 and 1:2. The Cu(II) and Fe(III) complexes with 5-CQA showed lower antioxidant properties, as estimated by the spectrophotometric methods with DPPH•, ABTS•+, and HO• radicals, than the ligand alone, whereas in the lipid peroxidation inhibition assay, the metal complexes revealed a higher antioxidant activity than 5-CQA. Cu(II) 5-CQA showed the highest pro-oxidant activity in the Trolox oxidation assays compared to the other studied compounds. The lipophilic parameters of the compounds were estimated using the HPLC method. 5-CQA and its complexes with Fe(III) and Cu(II) were not toxic to HaCaT cells in a tested concentration range of 0.15-1000 nM after a 24 h incubation time.

Enhanced Antioxidant Activity of Ursolic Acid by Complexation with Copper (II): Experimental and Theoretical Study.

The copper (II) complex of ursolic acid (Cu(II) UA) was synthesized and discussed in terms of its infrared, UV-visible spectra, quantum-chemical calculations at B3LYP/6-31G(d) level and antioxidant capacity. The copper (II) complex was stable in methanolic solution with the molar ratio metal:ligand 1:1. The data obtained by FT-IR confirmed the metal ion coordination through the carboxylate anion. The antioxidant properties of ursolic acid and its complex with Cu were discussed on the basis of energy of the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) and values of chemical reactivity parameters. The antiradical properties of ursolic acid and the Cu (II) complex were examined against DPPH• and HO• radicals, and the ferric reducing antioxidant power (FRAP) was examined. The Cu(II) complex showed higher antioxidant activity than ursolic acid, i.e., in DPPH• assay, the EC50 for UA was 47.0 mM, whereas, for Cu(II), UA EC50 = 19.5 mM; the FRAP value for UA was 20.8 µMFe2+, and 35.4 µMFe2+ for Cu(II) UA (compound concentration 3 mM). Although there was no distinct difference in the antioxidant activity against HO• between these two chemicals, they were both better HO• scavengers than DPPH• and showed different kinetics in the reaction with DPPH•.

Drug Design Strategies for the Treatment of Viral Disease. Plant Phenolic Compounds and Their Derivatives.

The coronavirus pandemic (SARS CoV-2) that has existed for over a year, constantly forces scientists to search for drugs against this virus. In silico research and selected experimental data have shown that compounds of natural origin such as phenolic acids and flavonoids have promising antiviral potential. Phenolic compounds inhibit multiplication of viruses at various stages of the viral life cycle, e.g., attachment (disturbance of the interaction between cellular and viral receptors), penetration (inhibition of viral pseudo-particle fusion to the host membrane), replication (inhibition of integrase and 3C-like protease), assembly and maturation (inhibition of microsomal triglyceride transfer protein (MTP) activity hydrolysis) and release (inhibition of secretion of apolipoprotein B (apoB) from infected cells). Phenolic compounds also indirectly influence on the viral life cycle by affecting the host cell's biochemical processes that viruses use for their own benefit. Phenolic compounds may inhibit the proteasomes and cellular deubiquitinating activity that causes an increase in the ubiquitinated proteins level in host cells. This, in turn, contributes to the lowering the available ubiquitin molecules that viruses could use for their own replication. One of the drug design strategy for the treatment of viral diseases may be an enhancement of the antiviral properties of phenolic compounds by metal complexation. Many studies have shown that the presence of a metal ion in the structure can significantly affect the affinity of the compound to key structural elements of the SARS CoV-2, such as Mpro protease, RNA-dependent RNA polymerase (RdRp) and spike protein. We believe that in the era of coronavirus pandemic, it is necessary to reconsider the search for therapeutics among well-known compounds of plant origin and their metal complexes.