Direct Scavenging Activity Research Articles

Synthesis, Molecular Docking Studies and Biological Evaluation of Thiazolyl Hydrazone Derivatives of Chromone-3-carbaldehyde as Potent Anti-Oxidant and Anti-Inflammatory Agents.

A series of 15 thiazolyl hydrazone derivatives of chromone-3- carbaldehyde have been designed and synthesized by the cyclization of thiosemicarbazone derivatives of chromone-3-carbaldehydes with 4'-substituted-2-bromo acetophenones. All these derivatives were evaluated for antioxidant activity by their direct scavenging activity objects to reactive oxygen species such as DPPH, and nitric oxide, as well as in vitro antiinflammatory activity by a protein denaturation method. Most of these synthesized compounds have shown significant antioxidant activity, among which the compounds 5b, 5c, 5e, 5g, and 5j showed very good antioxidant activities in comparison with the standard ascorbic acid. The in vitro anti-inflammatory activity revealed that the compounds 5b, 5g, and 5h possessed significant activity compared to standard diclofenac sodium. Additionally, molecular docking studies of these molecules using ovalbumin as the protein showed remarkable interactions with its active site residues, and the results indicated that the binding mode of these compounds closely resembled that of the reference compound, diclofenac sodium. Thus, these compounds represent an attractive template for the evaluation of new antiinflammatory and antioxidant agents and might be useful for exploring new therapeutic tools.

Free Radical Inhibition Using a Water-Soluble Curcumin Complex, NDS27: Mechanism Study Using EPR, Chemiluminescence, and Docking.

There is a growing interest in the use of natural compounds to tackle inflammatory diseases and cancers. However, most of them face the bioavailability and solubility challenges to reaching cellular compartments and exert their potential biological effects. Polyphenols belong to that class of molecules, and numerous efforts have been made to improve and overcome these problems. Curcumin is widely studied for its antioxidant and anti-inflammatory properties as well as its use as an anticancer agent. However, its poor solubility and bioavailability are often a source of concern with disappointing or unexpected results in cellular models or in vivo, which limits the clinical use of curcumin as such. Beside nanoparticles and liposomes, cyclodextrins are one of the best candidates to improve the solubility of these molecules. We have used lysine and cyclodextrin to form a water-soluble curcumin complex, named NDS27, in which potential anti-inflammatory effects were demonstrated in cellular and in vivo models. Herein, we investigated for the first time its direct free radicals scavenging activity on DPPH/ABTS assays as well as on hydroxyl, superoxide anion, and peroxyl radical species. The ability of NDS27 to quench singlet oxygen, produced by rose bengal photosensitization, was studied, as was the inhibiting effect on the enzyme-catalyzed oxidation of the co-substrate, luminol analog (L012), using horseradish peroxidase (HRP)/hydrogen peroxide (H2O2) system. Finally, docking was performed to study the behavior of NDS27 in the active site of the peroxidase enzyme.

Trans-resveratrol reduced hepatic oxidative stress in an animal model without inducing an upregulation of nuclear factor erythroid 2-related factor 2.

Trans-resveratrol, a widely used supplement for humans, aims to enhance the body's antioxidant defense. Studies suggest that it exerts anti-inflammatory and antioxidant effects by activating the nuclear factor erythroid 2-related factor 2 (Nrf2). In order to evaluate this hypothesis, LDLr(-/-) mice were fed a Western diet to induce liver inflammation and oxidative stress. One group was fed a diet containing 0.60 mg/day of trans-resveratrol (RESV), while another group received no dietary supplementation (CONT). Oxidative stress biomarkers and inflammatory cytokines were assessed in liver homogenates. It was observed that trans-resveratrol decreased hepatic oxidative stress by increasing the GSH/GSSG ratio and reducing malondialdehyde (MDA) concentration. However, the RESV group exhibited a reduction in Nrf2 relative expression compared to CONT. Additionally, trans-resveratrol supplementation reduced nuclear factor-κB (NF-κB) expression but led to an increase in IL-6, with no significant changes observed in tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) concentrations. Overall, these findings indicate that the in vivo antioxidant impact induced by trans-resveratrol supplementation in hepatic tissue did not correlate with increase of inflammatory cytokines and Nrf2 relative expression. Further exploration of alternative mechanisms, such as direct radical scavenger activity, is warranted to elucidate the antioxidant effect.

Sedation Therapy in Intensive Care Units: Harnessing the Power of Antioxidants to Combat Oxidative Stress.

In critically ill patients requiring intensive care, increased oxidative stress plays an important role in pathogenesis. Sedatives are widely used for sedation in many of these patients. Some sedatives are known antioxidants. However, no studies have evaluated the direct scavenging activity of various sedative agents on different free radicals. This study aimed to determine whether common sedatives (propofol, thiopental, and dexmedetomidine (DEX)) have direct free radical scavenging activity against various free radicals using in vitro electron spin resonance. Superoxide, hydroxyl radical, singlet oxygen, and nitric oxide (NO) direct scavenging activities were measured. All sedatives scavenged different types of free radicals. DEX, a new sedative, also scavenged hydroxyl radicals. Thiopental scavenged all types of free radicals, including NO, whereas propofol did not scavenge superoxide radicals. In this retrospective analysis, we observed changes in oxidative antioxidant markers following the administration of thiopental in patients with severe head trauma. We identified the direct radical-scavenging activity of various sedatives used in clinical settings. Furthermore, we reported a representative case of traumatic brain injury wherein thiopental administration dramatically affected oxidative-stress-related biomarkers. This study suggests that, in the future, sedatives containing thiopental may be redeveloped as an antioxidant therapy through further clinical research.

Antioxidant, Anti-Skin-Aging, Anti-Inflammatory, and Anti-Acetylcholinesterase Activities of Rourea oligophlebia Extracts.

The objective of this study was to evaluate the antioxidant, anti-skin-aging, anti-inflammatory, and anti-acetylcholinesterase activities of the hexane (n-hex), AcOEt, BuOH, MeOH, and aqueous extracts from R. oligophlebia roots. The total phenolic and flavonoid contents (TPC and TFC) were determined using Folin-Ciocalteu and AlCl3 colorimetric assays. The antioxidant capacity was examined by reducing power (RP), ferric reducing antioxidant power (FRAP), ABTS⋅+ , and DPPH⋅+ radical cation assays. All extracts potentially exhibited antioxidant activity with IC50 values ranging from 2.93 to 5.73 μg/mL for ABTS⋅+ and from 5.69 to 7.65 μg/mL for DPPH⋅+ except the n-hex extract. The BuOH, MeOH, and aqueous extract possess promising anti-skin-aging activities, as observed by an attenuation of UV-A toxicity on human keratinocytes. We proposed that these anti-skin-aging properties are possibly due to direct scavenging activity against reactive oxygen species and upregulate cellular antioxidant machinery. Moreover, we found that the antioxidant capacity was well correlated with anti-inflammatory capacity against nitric oxide (NO) production in terms of the n-hex, AcOEt, and BuOH extracts with IC50 values from 23.21 to 47.1 μg/mL. In contrast, these activities were found to be poorly correlated with AchE activity. To the best of our knowledge, this is the first report of the antioxidant, anti-skin-aging, anti-inflammatory, and anti-acetylcholinesterase activities of the extracts of R. oligophlebia roots. These findings indicated that this species could be a potential source of natural antioxidant, anti-aging, and anti-inflammatory agents. Consequently, it may be suggested as a medicinal plant that prevents diseases related to oxidative stress and inflammatory responses.

The dose-response relationships of the direct scavenging activity of amide-based local anesthetics against multiple free radicals.

This study aimed to illustrate the dose-response relationships of the direct scavenging activity of amide-based local anesthetics against multiple free radicals in vitro. We have demonstrated that amide-type local anesthetics selectively and directly scavenge some free radicals. Three kinds of free radicals were eliminated by all the four local anesthetics examined. Mepivacaine, lidocaine, bupivacaine, and dibucaine scavenged hydroxyl radicals in dose-dependent manners. Ascorbyl free radicals were also scavenged in dose-dependent manners, and lastly singlet oxygen was scavenged in dose-dependent manners. Three other free radicals were not scavenged by all of the four local anesthetics; tert-butoxyl radical was scavenged by all the anesthetics examined but dibucaine, nitric oxide by mepivacaine but not by the other three, and tyrosyl radical by mepivacaine and lidocaine but not by the other two. Some free radicals (superoxide anion, tert-butyl peroxyl radical, DPPH) were not scavenged by any of the four local anesthetics. The local anesthetics were also shown to inhibit lipid peroxidation by TBARS assay. These results suggest that local anesthetics have antioxidant properties through their free radical scavenging activities.

Antioxidant activity of caffeic acid: thermodynamic and kinetic aspects on the oxidative degradation pathway

Caffeic acid is a phenolic secondary metabolite from plants, which is known for its antioxidant properties. The effective mitigation of methanol-induced oxidative stress by caffeic acid depends on the direct radical scavenging as well as the formation of new metabolites via oxidative degradation. Herein, thermodynamic and kinetic aspects of the oxidative degradation pathway of caffeic acid in the presence of radical CH3O• and its isomer, •CH2OH are discussed for the first time, employing density functional theory (DFT). The direct radical scavenging activity of caffeic acid against these radicals is verified via hydrogen atom transfer (HAT) and radical adduct formation (RAF) mechanisms. HAT is predicted to be more feasible than RAF mechanism as per the computed data. Additionally, energetic details of the proposed oxidative degradation pathway of radical adduct intermediates toward the formation of a cyclic metabolite is analyzed. Kinetic studies indicated a significant tunneling contribution to the H abstraction pathways having high activation barriers. Further, our results imply that the newly formed metabolites exhibit comparable antioxidant activity with that of caffeic acid.

Prophylactic Protective Action of Aqueous Extract of Green Oak Acorns on Ethanol-Induced Acute Injury to Rat Gastroduodenal Mucosa.

Quercus ilex fruit is widely used in the treatment of various gastrointestinal disorders, including diarrhea, for its bioactive compounds and astringent property. The current study focuses on the phytochemical characterization of the Q. ilex-aqueous extract (QIAE) and its protective effect against gastroduodenal (GD) ulcer (GDU) produced by absolute ethanol (EtOH) intoxication in adult male Wistar rats. Experimental rats were divided into six groups (n = 6): control, EtOH [95%, 4 g/kg body weight (b.w.)], EtOH + different doses of QIAE (100, 200, and 400 mg/kg, b.w.), and EtOH + Famotidine (FAM, 10 mg/kg, b.w.). Animals were orally pretreated (p.o.) with QIAE for 15 days and intoxicated with a single oral administration of EtOH for 2 h. The findings showed that the QIAE is rich in phenolic-astringent compounds and fibers, and it exhibited a significant scavenging activity on DPPH/ABTS free-radicals with half maximal inhibitory concentration (IC50) values of 177.00 ± 5.11 and 203.9 ± 2.23 μg/mL, respectively. In vivo part, QIAE significantly reduced the GD mucosal injury revealed by edema and leukocyte infiltration of the submucosal layer. GD mucosal homogenates revealed a remarkable increase in endogenous antioxidant enzyme activities (catalase, superoxide dismutase, and glutathione peroxidase) and a decrease in the lipid peroxidation levels (malondialdehyde) in animals pretreated with QIAE compared with the ulcer control group. QIAE exerted significant and dose-dependent anti-GDU protection in the rat model with a more effective action than FAM. The GD protective effect of the QIAE might be related to a direct radical scavenging activity, increased antioxidant enzymes, and depression of lipid peroxidation.

Dose-dependent scavenging activity of the ultra-short-acting β1-blocker landiolol against specific free radicals.

Landiolol, a highly cardioselective ultra-short-acting β1-blocker, prevents perioperative atrial fibrillation associated with systemic inflammation and oxidative stress. We evaluated the direct scavenging activity of landiolol against multiple free radical species. Nine free radical species (hydroxyl, superoxide anion, ascorbyl, tert-butyl peroxyl, tert-butoxyl, singlet oxygen, 2,2-diphenyl-1-picrylhydrazyl, nitric oxide, and tyrosyl radicals) were directly quantified using an X-band ESR spectrometer with the spin-trapping method. IC50 and reaction rate constants were estimated from the dose-response curve for each free radical. Landiolol scavenged six of the free radical species examined: hydroxyl radical (IC50 = 0.76 mM, k landiolol = 1.4 × 10‍10 M‍-1 s‍-1, p<0.001), superoxide anion (58 mM, 2.1 M‍-1 s‍-1, p = 0.044), tert-butoxyl radical (4.3 mM, k landiolol/k CYPMPO = 0.77, p<0.001), ascorbyl free radical (0.31 mM, p<0.001), singlet oxygen (0.69 mM, k landiolol/k 4-OH ‍TEMP = 2.9, p<0.001), and nitric oxide (15 mM, 1.7 × 10 M‍-1 s‍-1, p<0.001). This study is the first to report that landiolol dose-dependently scavenges multiple free radical species with different reaction rate constants. These results indicate the potential clinical application of landiolol as an antioxidative and anti-inflammatory agent in addition to its present clinical use as an anti-arrhythmic agent.

Direct and Indirect Antioxidant Effects of Selected Plant Phenolics in Cell-Based Assays.

Background: Oxidative stress is a key factor in the pathophysiology of many diseases. This study aimed to verify the antioxidant activity of selected plant phenolics in cell-based assays and determine their direct or indirect effects. Methods: The cellular antioxidant assay (CAA) assay was employed for direct scavenging assays. In the indirect approach, the influence of each test substance on the gene and protein expression and activity of selected antioxidant enzymes was observed. One assay also dealt with activation of the Nrf2-ARE pathway. The overall effect of each compound was measured using a glucose oxidative stress protection assay. Results: Among the test compounds, acteoside showed the highest direct scavenging activity and no effect on the expression of antioxidant enzymes. It increased only the activity of catalase. Diplacone was less active in direct antioxidant assays but positively affected enzyme expression and catalase activity. Morusin showed no antioxidant activity in the CAA assay. Similarly, pomiferin had only mild antioxidant activity and proved rather cytotoxic. Conclusions: Of the four selected phenolics, only acteoside and diplacone demonstrated antioxidant effects in cell-based assays.

Theoretical insights into the direct radical scavenging activities of 8-hydroxyquinoline: Mechanistic, thermodynamic and kinetic studies

A Density Functional Theory study of the mechanisms, thermodynamics and kinetics of some antiradical reactions of 8-hydroxyquinoline (8HQ) against •OH is reported. The radical adduct formation (RAF), hydrogen atom transfer (HAT) and single electron transfer (SET) mechanisms are investigated. The results indicate that 8HQ is an efficient RAF-dependent direct •OH radical deactivator, in accordance with recent experimental findings that 8HQ is a potent scavenger of reactive oxygen species (ROS). The ortho and para carbons to the hydroxyl group in 8HQ, not including the bridgehead carbon, are identified as highly favorable RAF sites in polar and nonpolar solvents. Interestingly, RAF via the para carbon is thermodynamically feasible, fast (with apparent rate constants 2.867 × 108 and 1.012 × 107M-1s-1 in water and benzene, respectively), and contributes over 70% of 8HQ’s antioxidant capacity. Our results support the viewpoint that direct ROS scavenging plays a key role in 8HQ’s anti-neurodegenerative activities.

Evaluation of licorice (Glycyrrhiza glabra L.) as a novel microgreen from the anti-inflammatory potential of polyphenols

Literature on microgreens, an emerging new functional food crop, remains limited. Further study on microgreens as a promising dietary component for potential use in diet-based disease prevention is, therefore, essential. Given that the anti-inflammatory and anti-oxidant properties of mature licorice root material are well-documented, the objective of the present, preliminary study was to present licorice (<em>Glycyrrhiza glabra</em> L.) as a novel, edible fresh-food microgreen candidate. The effect of leaf, stem and root polyphenol extracts of 20-day old licorice microgreen seedlings on cell proliferation and viability of Caco-2 cells (simulating the intestinal epithelium), after pro-inflammatory induction of lipopolysaccharide (LPS), was examined and then compared to the polyphenol, flavonoid and anti-radical activities of the respective tissue extracts. Root extracts contained a two-fold less polyphenol (including flavonoid) content compared to leaf extracts, but with a five-fold lower anti-radical scavenging activity. Only the root extracts provided functional protection in terms of preserving cell proliferation and viability of LPS-treated Caco-2 cells. Some protection was also afforded by the stems, but the young leaf material offered no anti-inflammatory protection. Results point to a differing composition of anti-inflammatory polyphenols between the root and leaf, suggesting that the protective efficacy of the root extracts (and to some degree, the stem extracts) resides in inhibiting the pro-inflammatory cascade and resultant cytotoxic effects as opposed to a direct anti-radical scavenging activity. Potential use of licorice as a microgreen is promising, but will necessitate further study.

Antioxidant Mechanisms in the Neuroprotective Action of Cemtirestat: Studies in Chemical Models, Liposomes and Rat Brain Cortical Slices

Neuroprotective action of the novel aldose reductase (AR) inhibitor cemtirestat (CMT), 2-(3-thioxo-2H-[1,2,4]triazino[5,6-b]indol-5(3H)-yl)acetic acid, was recently proved in experimental rat models of diabetes. The in vivo results indicated that the antioxidant activity of this compound might have participated on its effects. The aim of this study was to explore in a greater detail the putative antioxidant mechanisms potentially involved in CMT mediated neuroprotection. Antioxidant efficacy per se of CMT was proved by a ferric reducing antioxidant power (FRAP) test and CMT was found to scavenge reactive oxygen species (ROS) generated in water phase chemically with decreasing efficacy as follows ROO > H2O2 > O2−. Studies in liposomes revealed the ability of CMT to inhibit lipid peroxidation more efficiently than melatonin, yet less effectively than Trolox. In the rat brain cortical slices, CMT reduced the loss of cell viability/mitochondrial function induced by quinolinic acid (QUIN), and inhibited lipid peroxidation. In addition, CMT normalized the GSH/GSSG ratio which could be explained, at least partially, by the ability of this compound to release free GSH from the pool of endogenously bound disulfides. Neuronal cell damage induced by QUIN or H2O2 was reduced by CMT as proved by significant drop in propidium iodide incorporation into cells. On balance then, our results corroborated the notion of a multifunctional action of CMT as a drug combining AR inhibition with direct antioxidant and ROS scavenging activity. Moreover, the ability of CMT to restore thiol-disulfide homeostasis was proved.

The Metabolite Urolithin-A Ameliorates Oxidative Stress in Neuro-2a Cells, Becoming a Potential Neuroprotective Agent.

Urolithin A is a metabolite generated from ellagic acid and ellagitannins by the intestinal microbiota after consumption of fruits such as pomegranates or strawberries. The objective of this study was to determine the cytoprotective capacity of this polyphenol in Neuro-2a cells subjected to oxidative stress, as well as its direct radical scavenging activity and properties as an inhibitor of oxidases. Cells treated with this compound and H2O2 showed a greater response to oxidative stress than cells only treated with H2O2, as mitochondrial activity (MTT assay), redox state (ROS formation, lipid peroxidation), and the activity of antioxidant enzymes (CAT: catalase, SOD: superoxide dismutase, GR: glutathione reductase, GPx: glutathione peroxidase) were significantly ameliorated; additionally, urolithin A enhanced the expression of cytoprotective peroxiredoxins 1 and 3. Urolithin A also acted as a direct radical scavenger, showing values of 13.2 μM Trolox Equivalents for Oxygen Radical Absorbance Capacity (ORAC) and 5.01 µM and 152.66 µM IC50 values for superoxide and 2,2-diphenyss1-picrylhydrazyl (DPPH) radicals, respectively. Finally, inhibition of oxidizing enzymes, such as monoamine oxidase A and tyrosinase, was also detected in a dose-dependent manner. The cytoprotective effects of urolithin A could be attributed to the improvement of the cellular antioxidant battery, but also to its role as a direct radical scavenger and enzyme inhibitor of oxidases.

Effects of Vitis vinifera L. leaves extract on UV radiation damage in human keratinocytes (HaCaT)

Vitis vinifera L. water extract from red grapevine leaves contains high levels of polyphenols in quantities similar to those found in red grape and grape seeds. Phenolic compounds are the largest group of natural antioxidants with also an anti-inflammatory activity, widely demonstrated both in vitro and in vivo. Interestingly, their antioxidant effect relies not only on the direct radical scavenging activity but also on their ability in modulating cellular signalling transduction pathways. UV radiation exerts multiple effects on skin cells inducing apoptosis, senescence and carcinogenesis. The aim of this study was to investigate the antioxidant and the DNA protective potentials of Vitis vinifera L. water extract against UV-A and UV-B radiation in HaCaT cells, a human keratinocytes cell line. Comet and ɣH2AX assays were used to assess DNA damage in UV irradiated cells pre-treated or not with the extract (100 μg/mL). For UV-B, DNA damage resulted significantly increased at 40 mJ/cm2 dose determining cell cycle arrest and apoptosis. For UV-A, DNA damage was significant at 10 J/cm2 while cell cycle arrest and apoptosis were evident only at 25 J/cm2. The extract (1h of pre-treatment) highlights the antioxidant and scavenger activity on the UV-A, while the maintenance of the apoptosis with both UV-A and UV-B must be interpreted as an anti-mutagenic effect.

INVESTIGATION OF THE NEUROPROTECTIVE EFFECT OF LINAGLIPTIN AND CELIPROLOL IN RESERPINE-INDUCED OROFACIAL DYSKINESIA AND ROTENONE-INDUCED NEURODEGENERATION IN RATS

Objective: Linagliptin, an anti-diabetic agent, proven to play an important role in regulating neuronal plasticity and reduce apoptosis and neuroinflammation by activating downstream AMPK/Sirt 1 pathway, which protects mitochondrial function and suppresses intracellular ROS accumulation and shows antioxidant action. Celiprolol, a β-1selective adrenoceptor blocker used as an anti-hypertensive agent, possesses a direct scavenging activity on oxygen radicals with antioxidant properties. The current study was designed to investigate the combined neuroprotective effect of linagliptin and celiprolol.&#x0D; Methods: Wistar rats of either sex were divided into different groups (n = 6). Eight groups each for Reserpine induced orofacial dyskinesia model and Rotenone induced neurodegeneration model to mimic Parkinson’s like conditions and treated or not with different doses of linagliptin and celiprolol. 24 h after the last dose, animals were subjected to behavioral, biochemical and histopathological evaluations. The data were analyzed by ANOVA and Bonferroni multiple comparison test.&#x0D; Results: Reserpine treatment increased VCMs, tongue protrusion and decreased locomotor activity. Rotenone treatment decreases the motor activity and exploratory ability of the animals. Reserpine as well as rotenone treatments decrease catalase, GSH, SOD and increase the LPO levels as compared to sham group animals. Reserpine and rotenone also showed the presence of ghost cells and vacuolated cytoplasm. Linagliptin and celiprolol alone as well as in combination normalized the behavioral, biochemical and histopathological complications.&#x0D; Conclusion: Linagliptin and Celiprolol showed neuroprotection by antioxidant activity as well as improved reserpine and rotenone-induced behavioral deficits. Both drugs have tenacious potential and can be used clinically with some further investigations.

Enhancing Lipid Oxidative Stability of Cooked‐Chilled Lamb Meat through Dietary Rosemary Diterpenes

AbstractA dietary rosemary extract (DRE) containing carnosic acid and carnosol at 1:1 (w/w) for enhancing the lipid oxidative stability in cooked‐chilled lamb meat, is evaluated. Three diets for fattening lambs are tested: i) a cereal‐based concentrate (C‐diet); ii) the C‐diet plus 600 mg vitamin E per kg feed (E‐diet); and iii) the C‐diet plus 600 mg rosemary diterpenes per kg feed (R‐diet). Griddled‐chilled lamb patties are kept at 4 °C and lighting for 2 days, simulating catering conditions. Diterpenes have a lower deposition rate than vitamin E in lamb muscle and are completely degraded during cooking. DRE is thus less effective than dietary vitamin E in enhancing the oxidative stability of the patties. After 2‐day storage, the R‐diet shows lower (p &lt; 0.01) peroxide values and thiobarbituric acid reactive substances than the C‐diet, while, in contrast to the E‐diet, it does not inhibit (p &gt; 0.05) the formation of cholesterol oxidation products. The R‐diet increases (p &lt; 0.05) the proportion of polyunsaturated fatty acids and decreases (p &lt; 0.05) the n‐6/n‐3 ratio. These findings suggest antioxidant protection by dietary bioactive compounds beyond the direct radical scavenging activity that is able to stabilize lipids during the meat shelf‐life.Practical Applications: Cooked‐chilled meat lipids strongly oxidize in ready‐to‐eat dishes kept in retailing conditions, which may negatively affect their levels of polyunsaturated fatty acids (PUFA), cholesterol oxidation products (COP), and other lipid oxidation products. Dietary rosemary diterpenes can be used as a clean alternative to feed additives to enhance the oxidative stability of cooked‐chilled meat. Improved health and antioxidant status of the animal might be able to reduce oxidative spoilage during meat shelf‐life. Diterpenes provide lesser antioxidant protection than dietary vitamin E but may improve the PUFA content, with positive implications for the nutritional quality of lamb fat. The use of dietary antioxidants with different properties may contribute to improving the efficacy of animal feeds to improve meat quality.

Edoxaban Exerts Antioxidant Effects Through FXa Inhibition and Direct Radical-Scavenging Activity.

The interplay between oxidative stress, inflammation, and tissue fibrosis leads to the progression of chronic kidney disease (CKD). Edoxaban, an activated blood coagulation factor Xa (FXa) inhibitor, ameliorates kidney disease by suppressing inflammation and tissue fibrosis in animal models. Interestingly, rivaroxaban, another FXa inhibitor, suppresses oxidative stress induced by FXa. Thus, FXa inhibitors could be multitargeted drugs for the three aforementioned risk factors for the progression of CKD. However, the exact mechanism responsible for eliciting the antioxidant effect of FXa inhibitors remains unclear. In this study, the antioxidant effect of edoxaban was evaluated. First, the intracellular antioxidant properties of edoxaban were evaluated using human proximal tubular cells (HK-2 cells). Next, direct radical scavenging activity was measured using the electron spin resonance and fluorescence analysis methods. Results show that edoxaban exhibited antioxidant effects on oxidative stress induced by FXa, indoxyl sulfate, and angiotensin II in HK-2 cells, as well as the FXa inhibitory activity, was involved in part of the antioxidant mechanism. Moreover, edoxaban exerted its antioxidative effect through its structure-specific direct radical scavenging activity. Edoxaban exerts antioxidant effects by inhibiting FXa and through direct radical-scavenging activity, and thus, may serve as multitargeted drugs for the three primary risk factors associated with progression of CKD.

OxiCyan®, a phytocomplex of bilberry (Vaccinium myrtillus) and spirulina (Spirulina platensis), exerts both direct antioxidant activity and modulation of ARE/Nrf2 pathway in HepG2 cells

• OxiCyan® is a phytocomplex based on bilberry and spirulina extracts. • The bilberry anthocyanin moiety exerts a direct effect on ROS quenching on HepG2 cells. • The constituents of spirulina induce ARE/Nrf2 pathway on HepG2 cells. • OxiCyan® is a strong antioxidant at the cellular level and triggers the natural antioxidant cell defense. The antioxidant activity of plant extracts requires compelling evidence of the physiological functions of antioxidants at the cellular level. In order to assess the antioxidant power of the phytocomplex OxiCyan®, a bilberry extract functionalized on spirulina, traditional chemical methods (DPPH and ABTS) were compared to in vitro cellular responses by using HepG2 human hepatocyte carcinoma 85011430 cell lines. OxiCyan® was found to act on HepG2 cells in a dual mode: with a direct effect on ROS scavenging and as a cytoprotective agent via induction of ARE/Nrf2 pathway. Direct ROS scavenging activity of OxiCyan® depended on the anthocyanin moiety provided by bilberry, whereas the gene activation of the ARE/Nrf2 pathway was triggered by spirulina chemical constituents. The comparative analysis of chemical and cellular assays indicated contrasting results. OxiCyan® showed a high antioxidant activity at the cellular level by both scavenging ROS and inducing the gene expression of natural antioxidant cell defense.

Effects of resveratrol in combination with 5-fluorouracil on N-methylnitrosourea-induced colon cancer in rats

5-Fluorouracil (5-FU) is the most commonly used therapy and the conventional treatment for colorectal cancer. However, its toxicity to normal tissues is considered a major obstacle to successful cancer chemotherapy; thus, resveratrol is used in combination with 5-FU to reduce its toxicity. The goal of our study is to investigate the mechanisms underlying the effects of resveratrol alone and in combination with 5-FU in inhibiting experimentally induced colon cancer. Rats were divided into eight groups including control, resveratrol, 5-FU, resveratrol with 5FU, N-methylnitrosourea, treated group 1, 2, and 3 groups. Oxidant/antioxidant parameters, plasma NF-κB, and real-time PCR quantification of colonic P53 gene expression were assessed. Histopathological and immunohistochemistry of cyclooxygenases (COX-1, COX-2) were also performed. The data showed that N-methylnitrosourea significantly increased colon malondialdehyde (MDA), advanced oxidation protein products (AOPP), and nuclear factor-κB (NF-κB) concomitant with a reduction in superoxide dismutase (SOD) and a downregulation in P53 gene expression. Supplementation with resveratrol improved these values in treated groups. Thus, resveratrol is a highly promising antioxidant, anti-cancer, and anti-inflammatory compound through activating antioxidant defense system, its direct scavenging activity, as well as its biological activities through downregulation of COX-2 via suppression of NF-κB activation.