Modulation of Oxidative Stress and Neuroinflammation by Cannabidiol (CBD): Promising Targets for the Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disease and the most common form of dementia globally. Although the direct cause of AD remains under debate, neuroinflammation and oxidative stress are critical components in its pathogenesis and progression. As a result, compounds like cannabidiol (CBD) are being increasingly investigated for their ability to provide antioxidant and anti-inflammatory neuroprotection. CBD is the primary non-psychotropic phytocannabinoid derived from Cannabis sativa. It has been found to provide beneficial outcomes in a variety of medical conditions and is gaining increasing attention for its potential therapeutic application in AD. CBD is not psychoactive and its lipophilic nature allows its rapid distribution throughout the body, including across the blood-brain barrier (BBB). CBD also possesses anti-inflammatory, antioxidant, and neuroprotective properties, making it a viable candidate for AD treatment. This review outlines CBD's mechanism of action, the role of oxidative stress and neuroinflammation in AD, and the effectiveness and limitations of CBD in preclinical models of AD.

Antimicrobial efficiency against fish pathogens on the green synthesized silver nanoparticles.

Fish-borne pathogens such as A. hydrophila and F. aquidurense are the most resistant strains in pisciculture farming. Removing the aforementioned pathogens without antibiotics presents a formidable challenge. To overcome this problem, silver nanoparticles (AgNPs) are synthesized using silver nitrate, water medium, and as an AzadirachtaIndica leaf extract via the green synthesis route. X-ray diffraction (XRD) pattern results authenticate the synthesized material is the face-centered cubic structure of silver. The optical absorption edge of the synthesized product was found at the wavelength of 440 nm from the UV-visible spectra, which is confirmed to relate to the Surface Plasmon Resonance peaks of silver particles. In addition, the optical band gap value of the synthesized Ag sample is measured to be 2.81 eV from the obtained optical absorption spectra. EDX spectrum of the synthesized product also supports confirming the silver particle formation. The FT-IR spectra of the neem extract and silver nanoparticles showed their characteristic functional groups, respectively. The presence of bands between 1000 cm-1 to 500 cm-1 indicates to the formation of silver particles. Spherical particles appeared in the synthesized Ag using Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM). The particle size of Ag NPs was measured as 40 nm and 62 ± 10 nm by TEM and Dynamic Light Scattering (DLS). The zeta potential was also measured as -12 mV showing the synthesized sample's stable nature. Using the DPPH assay, synthesized AgNPs were taken along with the various concentrations of ascorbic acid (20, 40, 60, 80, and 100 µg/mL) to examine the free radical scavenging activity (RSA). RSA value is higher (84 ± 2 %) for synthesized AgNPs at higher concentration (100 µg/mL) than 21 ± 2 % at low concentration (100 µg/mL). The antimicrobial efficacy of the AgNPs against A. hydrophila and F. aquidurense was performed through the agar diffusion method and its results showed the inhibitory zones of the F.aquidurense and A. hydrophila were measured as 25 ± 3 mm, and 28 ± 4 mm respectively. The synthesized Ag particles showed excellent antimicrobial and antioxidant properties confirmed by antimicrobial and DPPH experiments. It implies that the green synthesized silver nanoparticles could be a good alternative for antibiotics in aquaculture farms. The exposure of low concentrations of silver nanoparticles to zebrafish and brine shrimp does not affect the viability and morphology. The exposure of silver nanoparticles in the fisheries in optimized concentration and time could control the fish-borne pathogens without antibiotics.

Chemical Composition, Antioxidant, and Antibacterial Activity of Ruta chalepensis L. Ethanolic Extract.

Ruta chalepensis L. is a versatile herb used in culinary arts and traditional medicine. The study aimed to determine the chemical composition of an ethanolic extract from R. chalepensis and the total phenolic and flavonoid content. Additionally, the extracts' antimicrobial and antioxidant activities were tested. The disc diffusion method and minimum inhibitory concentration (MIC) were used to test the antibacterial properties on four types of bacteria: Escherichia coli, Proteus penneri, Bacillus cereus, and Staphylococcus aureus. A colorimetric assay was used to evaluate the total phenolic and flavonoid content, and the DPPH method was used to assess the antioxidant activity. The phytochemical constituents were determined using LC-MS/MS. The results indicated that R. chalepensis ethanolic extract had 34 compounds, and the predominant compounds were quercetin (9.2 %), myricetin (8.8 %), and camphene (8.0 %). Moreover, the extract had a good level of polyphenols and flavonoids, as demonstrated by inhibiting free radicals (DPPH) (IC50 was 41.2±0.1). Also, the extract exhibited robust antimicrobial activity against P. penneri and S. aureus with an MIC of 12.5 and 25.0 µg/mL, respectively. In conclusion, the results suggest that the R. chalepensis ethanolic extract has good antioxidant and antibacterial properties that could be utilized to develop new antibacterial agents.

Assessment of Moroccan Cannabis Sativa Seed Oil: Chemical Analysis and Evaluation of Antioxidant, Toxicological, and Antinociceptive Effects.

Assessment of Moroccan Cannabis sativa Seed Oil: Chemical Analysis and Evaluation of Antioxidant, Toxicological, and Antinociceptive Effects. by K. Raoui et al., Cadi Ayyad University, Marrakech, Morocco. Cannabis sativa L., locally known as "El kif", belongs to the Cannabaceae family. This study aims to conduct a chemical analysis of Cannabis sativa seed oil (CSSO) and assess its acute toxicity, antioxidant properties, and analgesic effects. The chemical analysis was performed using gas chromatography and mass spectrometry (GC/MS) to identify fatty acids (FAs) contents. Antioxidant activity was evaluated in vitro using the (2,2-diphenyl-1-picrylhydrazyl) DPPH radical scavenging method and the (ferric reducing antioxidant power) FRAP method. Concurrently, acute toxicity, along with antinociceptive activity, was studied through three distinct animal models: writhing test, formalin test, and hot plate test. The results revealed that linoleic acid, oleic acid, α-linolenic acid, and palmitic acid were the main components of CSSO. The LD50 of CSSO was greater than 5 g/kg, indicating low toxicity. Additionally, CSSO exhibited a significant content of flavonoids and total polyphenols, along with notable antioxidant activity with important values. The results indicated a significant increase in thermal stimulus latency, a reduction in the number of writhes induced by acetic acid, and a decrease in licking time in both phases of the formalin test. In conclusion, this study suggests promising results for CSSO, emphasizing its potential as a therapeutic agent.

Effects of Sequential Induction Combining Thermal Treatment with Ultrasound or High Hydrostatic Pressure on the Physicochemical and Mechanical Properties of Pea Protein-Psyllium Hydrogels as Elderberry Extract Carriers.

Entrapping bioactive ingredients like elderberry extract in hydrogels improves their stability and functionality in food matrices. This study assessed the effect of sequential thermal treatment with ultrasound (US) or high hydrostatic pressure (HHP) and treatment duration on pea protein-psyllium hydrogels as elderberry extract carriers. Measurements included color parameters, extract entrapment efficiency, physical stability, textural properties, microrheology, FT-IR, thermal degradation (TGA), SEM images, total polyphenols content, antioxidant activity, and reducing power. The control hydrogel was obtained using only thermal induction. Both treatments impacted physical stability by affecting biopolymer aggregate structures. Thermal and US combined induction resulted in hydrogels with noticeable color changes and reduced entrapment efficiency. Conversely, thermal and HHP-combined induction, especially with extended secondary treatment (10 min), enhanced hydrogel strength, uniformity, and extract entrapment efficiency (EE = 33% for P10). FT-IR and TGA indicated no chemical structural alterations post-treatment. Sequential thermal and HHP induction preserved polyphenol content, antioxidant activity (ABTS = 5.8 mg TE/g d.m.; DPPH = 11.1 mg TE/g d.m.), and reducing power (RP = 1.08 mg TE/g d.m.) due to the dense hydrogel structure effectively enclosing the elderberry extract. Sequential thermal and HHP induction was more effective in developing pea protein-psyllium hydrogels for elderberry extract entrapment.

Enhanced Hydrogel Materials: Incorporating Vitamin C and Plant Extracts for Biomedical Applications.

In recent years, the utilization of natural components has become crucial across various industries, including medicine. Particularly in biomedical contexts, hydrogel materials are of significant importance. Therefore, the objective of this research was to develop and analyze hydrogel materials infused with vitamin C. A key focus of this study was to conduct multiple syntheses with varying levels of vitamin C to explore the feasibility of creating materials with adjustable properties. The produced hydrogels underwent comprehensive physicochemical evaluation. The findings of this examination verified the correlation between the vitamin C content and the specific characteristics of the hydrogels. It was determined from these results that the samples displayed both sorptive and antioxidative capabilities, enabling their potential application in wound dressings or other biomedical uses. A notable benefit of these hydrogels is their adaptability, allowing for modifications to achieve desired attributes tailored to particular applications.

Analytical Assessment of the Antioxidant Properties of the Coneflower (Echinacea purpurea L. Moench) Grown with Various Mulch Materials.

Antioxidants are added to foods to decrease the adverse effect of reactive species that create undesirable compounds that destroy essential nutrients and, therefore, lower the nutritional, chemical and physical properties of foods. This study was carried out to determine the antioxidant properties of flowers and plant stems with leaves of Echinacea purpurea grown with mulches of different colours and thicknesses. Coneflowers were grown in the Experimental Station of the Agricultural University in Kraków, Poland. The mulching materials used were black, green and brown colours of 100 g/m2 and 80 g/m2 density. In plant material, e.g., flowers or plant stems plus leaves the proximate analysis, the total polyphenol content and the ability to scavenge free radicals (ABTS, DPPH and FRAP) were determined. The results show that flower samples had a higher content of compound proteins, ash and phenolic compounds. The mulching colour and density did not affect the proximate analysis of the E. purpurea plant. Based on the result of this study, E. purpurea is a potential source of natural antioxidants and can be used to improve the antioxidant activity of various food products as well as in cosmetics within the pharmaceutical industry.

Evaluation of the potential of achachairu peel (Garcinia humilis) for the fortification of cereal-based foods.

BACKGROUND: Achachairu is an exotic fruit that is being studied for its bioactive compound composition. However, there is scarce information on the properties of its by-products and their incorporation into food. In this study, achachairu peels were used to obtain phenolic-rich and sustainable ingredients. Furthermore, their potential for use in the fortification of food, particularly cereal-based products, was evaluated. Different ratios of ethanol:water were used to extract the phenolic compounds from achachairu (100:0, 90:10 and 70:30). The optimal extract was characterised regarding its total phenolic content (TPC) and antioxidant, antimicrobial and anti-enzymatic properties. Finally, achachairu peel powder and extract were incorporated into bread and their influence on the texture, antioxidant properties and shelf life of the product was evaluated. RESULTS: High-performance liquid chromatographic analysis showed that the 90:10 extract contained a higher phenolic composition than the other samples. The achachairu extract presented a TPC of 88.7 mgGAE g-1, good antioxidant capacity towards DPPH and ABTS radicals and the capacity to inhibit the activity of α-amylase by almost 80%. The addition of achachairu peel powder and extract to bread increased its hardness, chewiness and gumminess, not affecting the remaining texture parameters. An increase in the TPC, antioxidant properties and shelf life of the product was also observed. CONCLUSION: This study proves the potential for achachairu by-products incorporated into cereal-based products to improve their biological properties while extending the food shelf life. © 2024 Society of Chemical Industry.

Comparative study of dietary phenols with Tartary buckwheat protein (2S/13S): impact on structure, binding sites and functionality of protein.

BACKGROUND: This research was to investigate the interaction mechanism between 2S albumin and 13S globulin (2S and 13S, the most important storage proteins in Tartary buckwheat seeds) and three phenols (rutin, quercetin and myricetin) regarding the structural and antioxidant properties of their complexes. RESULTS: There are differences in the binding affinity of phenols for 2S and 13S. Rutin had a higher binding affinity for 2S, myricetin had a higher binding affinity for 13S, and 13S exhibited a higher affinity toward phenols than did 2S. Binding with phenols significantly changed the secondary and tertiary structures of 2S and 13S, decreased the surface hydrophobic value and enhanced the antioxidant capacity. Molecular docking and isothermal titration calorimetry showed that the binding processes were spontaneous and that there were hydrogen bonds, hydrophobic bonds and van der Waals force interactions between phenols and proteins. CONCLUSION: These findings could provide meaningful guidance for the further application of buckwheat protein complex. © 2023 Society of Chemical Industry.

Riboflavin improves grain yield, 2-acetyl-1-pyrroline accumulation, and antioxidative properties of fragrant rice.

BACKGROUND: Riboflavin, a vital water-soluble vitamin with antioxidative activity, plays a critical role in maintaining overall bodily health and defense responses. However, its impact on fragrant rice yield and aroma remains unexplored. RESULTS: In a 2022 pot experiment with Meixiangzhan and Yuxiangyouzhan fragrant rice cultivars, we applied riboflavin foliar treatments at concentrations of 0 (CK), 10 (R10), 20 (R20), and 40 (R40) mg L-1 during the initial heading stage. Riboflavin increased rice yield, 2-acetyl-1-pyrroline (2-AP) content, and antioxidative properties. It boosted 2-AP level by 13.1-50.1% for Meixiangzhan and 22.3-35.3% for Yuxiangyouzhan, with the highest levels in R20 and R10 treatments. This increase is significantly correlated with elevated levels of proline, pyrroline-5-carboxylic acid, pyrroline, and methylglyoxal, as well as heightened enzyme activities, including those of proline dehydrogenase, ornithine aminotransferase, and pyrroline-5-carboxylic acid synthetase (P5CS). The R20 treatment resulted in the highest yield due to an improved seed-setting rate. Importantly, a positive correlation emerged between 2-AP content and yield, both significantly linked to superoxide dismutase, proline, hydrogen peroxide, P5CS, catalase, and pyrroline. CONCLUSION: Riboflavin maintained enzyme activities, regulated substance synthesis pathways, and increased 2-AP and yield, especially in the R20 treatment. These insights advance fragrant rice production theory by uncovering riboflavin's role in the development of fragrant rice. © 2023 Society of Chemical Industry.

Production and Evaluation of Set-Type Yoghurt Fortified with Chlorella vulgaris and Moringa oleifera Powder.

Considering the growing popularity of functional foods, fortifying yoghurt with natural ingredients with various flavours and appearances could improve its nutritional and health potential. The current study aimed to evaluate the effect of Chlorella vulgaris (0.3 and 0.5%) and Moringa oleifera (0.3 and 0.5%) on the fermentation kinetics, apparent viscosity, antioxidant activity, microbiological, sensorial, and FTIR properties of yoghurt during storage. The results demonstrated that the incorporation of Chlorella vulgaris and Moringa oleifera into yoghurt increased acidification rate and decreased fermentation time (p < 0.05). Moringa oleifera (0.5%) improved the growth and survival of lactic acid bacteria as well as the phenolic and antioxidant properties of yoghurt. However, Chlorella vulgaris, at a concentration of 0.5% reduced the viability of lactic acid bacteria, viscosity, total phenolic, and antioxidant properties of yoghurt. In conclusion, it was found that Chlorella vulgaris, at 0.3%, and Moringa oleifera improved the phenolic, antioxidant properties, and acidification rate of yoghurt.

Optimisation of multigrain seera from sorghum, green gram and finger millet: effect of ingredients on functional, structural and thermal properties.

Seera, is a traditional Indian fermented food, has high carbohydrate and reducing sugar content, however, lacks functional components like antioxidant properties. The present study aims to optimize and evaluate the multigrain seera with added values. The optimization of seera was made using mixture design, with green gram (X1, 15-30%), sorghum (X2, 15-25%) and finger millet (X3, 5-10%) as independent variables. The responses checked were total phenolic content (Y1), protein content (Y2) and overall acceptability (Y3). The optimum run with green gram (25.58%), sorghum (15%) and finger millet (9.41%) resulted in TPC (1.2 ± 0.12 mg GAE/g), protein content (11.40 ± 0.10 g) with overall acceptability (8.32 ± 0.30). The optimized multigrain seera depicted higher fibre (4.23 ± 0.08%), ash (1.90 ± 1.1%) and protein (11.40 ± 0.10%) than the control seera. The rheological properties of seera depicted shear thinning and elastic behaviour. Texture profile analysis showed that cohesiveness (0.415 ± 0.01) increased significantly (along with decreased springiness (0.251). Morphology of seera showed broken and deformed starch granules with few cracks due to fermentation phenomena that leads to superficial corrosion. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05854-5.

An overview of different homogenizers, their working mechanisms and impact on processing of fruits and vegetables.

Fruits and vegetables (F&V) are the second highest recommended foods, rich in antioxidants, vitamins and minerals, vital for building immunity against chronic diseases. F&V processing involves particle size reduction, for which different types of homogenizers, categorized as mechanical homogenizers, pressure homogenizers and ultrasonic homogenizers are used. The review discusses different types of homogenizers, their working mechanism, and application in F&V processing. Among mechanical homogenizers, knife mills are used for primary size reduction, ball mills for the micronization of dried F&V and rotor-stator homogenizers for emulsification. Use of the ultrasonic homogenizer is limited to extraction of bioactive compounds or as a pre-treatment for dehydration of F&V. High-pressure homogenizers are most widely used and reported due to the synergistic effect of homogenization and temperature increase, resulting in longer shelf-life and better physicochemical properties of the product. Additionally, the review also explains the effect of homogenization on the physicochemical, sensory and nutraceutical properties of the product.

Pristine, carboxylated, and hybrid multi-walled carbon nanotubes exert potent antioxidant activities in in vitro-cell free systems.

Multi-walled carbon nanotubes (MWCNTs) are tubular-shaped carbon allotropes, composed of multiple concentric graphene cylinders. The extended systems of conjugated double bonds, that MWCNTs are constituted by, provide them with high electron affinities, enabling them to act as electron donors or acceptors. Consequently, their potential biomedical applications, as synthetic antioxidant agents, are of particular interest. Based on the above, the purpose of the present study was to evaluate the intrinsic antioxidant properties of pristine and carboxylated MWCNTs, as well as of novel hybrid nanocomposites of MWCNTs and inorganic nanoparticles. To this end, after the synthesis and characterization of MWCNTs, their antiradical, reducing, and antigenotoxic properties were assessed in cell-free assays, using a methodological approach that has been recently proposed by our research group. According to our results, most of the tested MWCNTs exhibited strong antioxidant activities. More elaborately, the hybrid material of MWCNTs and ferrous oxide nanoparticles, i.e., CNTs@Fe3O4, showed robust scavenging capacities in all free-radical scavenging assays examined. As regards reducing properties, the pristine MWCNTs, i.e., CNTs-Ref, exhibited the greater electron donating capacity. Finally, in terms of antigenotoxic properties, the hybrid material of MWCNTs and silicon carbide nanoparticles, i.e., CNTs@SiC, exhibited potent ability to inhibit the formation of peroxyl radicals, thus preventing from the oxidative DNA damage. Conclusively, our findings suggest that the MWCNTs of the study could be considered as promising broad-spectrum antioxidants, however, further investigations are required to evaluate their toxicological profile in cell-based and in vivo systems.

Synthesis and Antioxidant Properties of Psoralen Derivatives.

Five psoralen derivatives were synthesized and the structures of them were characterized by 1 H-NMR, 13 C-NMR, and IR. The antioxidant properties of the compounds were tested by inhibiting the free radical-initiated DNA oxidation and scavenging the radical reaction. The results showed that the effective stoichiometric factors (n) of the compounds V and IV could reach 2.00 and 2.11 in the system of inhibiting the DNA oxidation reaction initiated by 2,2'-Azobis(2-methylpropionamidine) dihydrochloride (AAPH). In the inhibition of ⋅OH-oxidation of the DNA system, compounds I~V showed antioxidant properties. The thiobarbituric acid absorbance (TBARS) percentages of compounds IV and V were 76.19 % and 78.84 %. Compounds I~V could also inhibit Cu2+ /GSH-oxidation of DNA, and all compounds exhibited good antioxidant properties except compound II (94.00 %). All the five compounds were able to trap diammonium 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonate) salt radical (ABTS+ ⋅), 2,2-diphenyl-1-picrylhydrazyl radical (DPPH⋅) and 2,6-di-tert-butyl-alpha-(3,5-di-tert-butyl-4-oxo-2,5-cyclohexadien-p-tolylox radical (galvinoxyl⋅). The ability of compounds I~V to scavenge those free radicals can be measured by the k values. The k values ranged from 0.07 to 0.82 in scavenging ABTS+ ⋅, galvinoxyl, and DPPH radicals, respectively.

Artificial Intelligence in Decrypting Cytoprotective Activity under Oxidative Stress from Molecular Structure.

Artificial intelligence (AI) is widely explored nowadays, and it gives opportunities to enhance classical approaches in QSAR studies. The aim of this study was to investigate the cytoprotective activity parameter under oxidative stress conditions for indole-based structures, with the ultimate goal of developing AI models capable of predicting cytoprotective activity and generating novel indole-based compounds. We propose a new AI system capable of suggesting new chemical structures based on some known cytoprotective activity. Cytoprotective activity prediction models, employing algorithms such as random forest, decision tree, support vector machines, K-nearest neighbors, and multiple linear regression, were built, and the best (based on quality measurements) was used to make predictions. Finally, the experimental evaluation of the computational results was undertaken in vitro. The proposed methodology resulted in the creation of a library of new indole-based compounds with assigned cytoprotective activity. The other outcome of this study was the development of a validated predictive model capable of estimating cytoprotective activity to a certain extent using molecular structure as input, supported by experimental confirmation.

Alginate Beads Containing Cerium-Doped Mesoporous Glass and Curcumin: Delivery and Stabilization of Therapeutics.

Cancer is a leading cause of death worldwide, its genesis and progression are caused by homeostatic errors, and reactive oxygen species play a major role in promoting aberrant cancer homeostasis. In this scenario, curcumin could be an interesting candidate due to its versatile antioxidant, anti-inflammatory, anti-tumor, anti-HIV, and anti-infection properties. Nonetheless, the major problem related to its use is its poor oral bioavailability, which can be overcome by encapsulating it into small particles, such as hydrogel beads containing mesoporous silica. In this work, various systems have been synthesized: starting from mesoporous silica glasses (MGs), cerium-containing MGs have been produced; then, these systems have been loaded with 4 to 6% of curcumin. Finally, various MGs at different compositions have been included in alginate beads. In vitro studies showed that these hybrid materials enable the stabilization and effective delivery of curcumin and that a synergic effect can be achieved if Ce3+/Ce4+ and curcumin are both part of the beads. From swelling tests, it is possible to confirm a controlled curcumin release compartmentalized into the gastrointestinal tract. For all beads obtained, a curcumin release sufficient to achieve the antioxidant threshold has been reached, and a synergic effect of cerium and curcumin is observed. Moreover, from catalase mimetic activity tests, we confirm the well-known catalytic activity of the couple Ce3+/Ce4+. In addition, an extremely good radical scavenging effect of curcumin has been demonstrated. In conclusion, these systems, able to promote an enzymatic-like activity, can be used as drug delivery systems for curcumin-targeted dosing.

Protective Properties of Spheroidal Taxifolin Form in Streptozotocin-Induced Diabetic Rats.

One of the key factors in the pathogenesis of diabetes and its complications is oxidative stress. To inhibit this process, antioxidants may be helpful. Herein, we focused on the protective properties of taxifolin spheroidal form (TS) in the streptozotocin rat model of diabetes mellitus. After 4 weeks of treatment with TS, the fasting blood glucose level of the diabetic animals decreased by 12% compared with the level right after the injection of streptozotocin. While the feed intake in the untreated diabetic rats increased by 5.3% compared with the healthy group, the TS-treated group showed a pronounced 15.3% decrease. Therapeutic administration of TS has a protective effect on the pancreas and the liver against the cytotoxic action of streptozotocin. The plasma antioxidant capacity of all diabetic groups appeared to be approximately 15% lower than in healthy rats with no significant difference between the TS-treated and untreated diabetic animals. Apparently, this can be attributed to taxifolin and plasma proteins binding. These data demonstrate the potential of TS in antidiabetic therapy.

Studies on the Anticancer and Antioxidant Activities of Resveratrol and Long-Chain Fatty Acid Esters.

Resveratrol (RES) is gaining recognition as a natural bioactive compound. To expand the possible applications of RES with its enhanced bioactivity as well as to increase the health benefits of long-chain fatty acids, a lipophilization process of RES was performed using three fatty acids: palmitic acid (PA), oleic acid (OA), and conjugated linoleic acid (CLA). The obtained mono-, di-, and tri-esters of RES were evaluated for their anticancer and antioxidant properties against lung carcinoma (A549), colorectal adenocarcinoma (HT29), and pancreatic ductal adenocarcinoma (BxPC3) cell lines. Human fibroblast (BJ) cells were used as a control. Several parameters were investigated: cell viability and apoptosis, including the expression of major pro- and anti-apoptotic markers, as well as the expression of superoxide dismutase, a key enzyme of the body's antioxidant barrier. Three of the obtained esters: mono-RES-OA, mono-RES-CLA, and tri-RES-PA, which significantly reduced the tumor cell viability up to 23%, at concentrations 25, 10, 50 µg/mL, respectively, turned out to be particularly interesting. The above-mentioned resveratrol derivatives similarly increased the tumor cells' apoptosis by modifying their caspase activity of pro-apoptotic pathways (p21, p53, and Bax). Moreover, among the mentioned esters, mono-RES-OA induced apoptosis of the analyzed cell lines most strongly, reducing the number of viable cells up to 48% for HT29 cells versus 36% for pure RES. Furthermore, the selected esters exhibited antioxidant properties towards the normal BJ cell line by regulating the expression of major pro-antioxidant genes (superoxide dismutases-SOD1 and SOD2) without the effect on their expression in the tumor, and therefore reducing the defense of cancer cells against increased oxidative stress induced by high ROS accumulation. The obtained results indicate that the esters of RES and long-chain fatty acids allow enhancement of their biological activity. The RES derivatives have the potential for being applied in cancer prevention and treatment, as well as for oxidative stress suppression.

Copper(II) Complexes with 1-(Isoquinolin-3-yl)heteroalkyl-2-ones: Synthesis, Structure and Evaluation of Anticancer, Antimicrobial and Antioxidant Potential.

Four copper(II) complexes, C1-4, derived from 1-(isoquinolin-3-yl)heteroalkyl-2-one ligands L1-4 were synthesized and characterized using an elemental analysis, IR spectroscopic data as well as single crystal X-ray diffraction data for complex C1. The stability of complexes C1-4 under conditions mimicking the physiological environment was estimated using UV-Vis spectrophotometry. The antiproliferative activity of both ligands L1-4 and copper(II) compounds C1-4 were evaluated using an MTT assay on four human cancer cell lines, A375 (melanoma), HepG2 (hepatoma), LS-180 (colon cancer) and T98G (glioblastoma), and a non-cancerous cell line, CCD-1059Sk (human normal skin fibroblasts). Complexes C1-4 showed greater potency against HepG2, LS180 and T98G cancer cell lines than etoposide (IC50 = 5.04-14.89 µg/mL vs. IC50 = 43.21->100 µg/mL), while free ligands L1-4 remained inactive in all cell lines. The prominent copper(II) compound C2 appeared to be more selective towards cancer cells compared with normal cells than compounds C1, C3 and C4. The treatment of HepG2 and T98G cells with complex C2 resulted in sub-G1 and G2/M cell cycle arrest, respectively, which was accompanied by DNA degradation. Moreover, the non-cytotoxic doses of C2 synergistically enhanced the cytotoxic effects of chemotherapeutic drugs, including etoposide, 5-fluorouracil and temozolomide, in HepG2 and T98G cells. The antimicrobial activities of ligands L2-4 and their copper(II) complexes C2-4 were evaluated using different types of Gram-positive bacteria, Gram-negative bacteria and yeast species. No correlation was found between the results of the antiproliferative and antimicrobial experiments. The antioxidant activities of all compounds were determined using the DPPH and ABTS radical scavenging methods. Antiradical tests revealed that among the investigated compounds, copper(II) complex C4 possessed the strongest antioxidant properties. Finally, the ADME technique was used to determine the physicochemical and drug-likeness properties of the obtained complexes.