Metabolites with Antioxidant Activity from Marine Macroalgae

Reactive oxygen species (ROS) attack biological molecules, such as lipids, proteins, enzymes, DNA, and RNA, causing cellular and tissue damage. Hence, the disturbance of cellular antioxidant homeostasis can lead to oxidative stress and the onset of a plethora of diseases. Macroalgae, growing in stressful conditions under intense exposure to UV radiation, have developed protective mechanisms and have been recognized as an important source of secondary metabolites and macromolecules with antioxidant activity. In parallel, the fact that many algae can be cultivated in coastal areas ensures the provision of sufficient quantities of fine chemicals and biopolymers for commercial utilization, rendering them a viable source of antioxidants. This review focuses on the progress made concerning the discovery of antioxidant compounds derived from marine macroalgae, covering the literature up to December 2020. The present report presents the antioxidant potential and biogenetic origin of 301 macroalgal metabolites, categorized according to their chemical classes, highlighting the mechanisms of antioxidative action when known.

Usnic Acid as a Potential Free Radical Scavenger and its Inhibitory Activity Toward SARS-CoV-2 Proteins

The antioxidative activity and free radical scavenging potency of usnic acid towards eight selected free radical species are examined. The thermodynamic parameters in the absence of harmful free radicals are used to predict the most favorable mechanism of antioxidative action. The reaction enthalpies are used to define the most probable mechanism of free radical scavenging in the presence of free radical species. The obtained results indicate that the favorable mechanism of antiradical action is dependent both on the polarity of solvents and the nature of free radical species. From the achieved results, it is clear that Sequential Proton Loss Electron Transfer (SPLET) is the most probable for antioxidative action in water and methanol, while competition between SPLET and Hydrogen Atom Transfer (HAT) is presented in benzene. The free radical scavenging of eight free radical species under investigation is possible, and the most believable mechanism of action is SPLET, in all three investigated solvents. Since usnic acid exhibits significant radical scavenging activity that affects the maintenance of redox hemostasis, its inhibitory potency toward COVID-19 targeted proteins molecular docking study is performed. The obtained results indicate that usnic acid has the potential to inhibit the functional proteins of SARS-CoV-2.

Advantageous/Unfavorable Effect of Quercetin on the Membranes of SK-N-SH Neuroblastoma Cells

Quercetin is a polyphenolic compound, the effects of which raise scientists’ doubts. The results of many experiments show that it has anticancer, antiinflammatory, and antioxidant properties, while other studies indicate its pro-oxidative and cytotoxic action. This compound can react with reactive oxygen species, and due to its chemical properties, it can be found in the hydrophobic-hydrophilic area of cells. These features of quercetin indicate that its action in cells will be associated with the modification of membranes and its participation in maintaining the redox balance. Therefore, this study distinguishes these two mechanisms and determines whether they are important for cell function. We check: (1) Whether the selected concentrations of quercetin are cytotoxic and destructive for SK-N-SH cell membranes (MTT, LDH, MDA tests) in situations with and without the applied oxidative stress; (2) what is the level of changes in the structural/mechanical properties of the lipid part of the membranes of these cells due to the presence of polyphenol molecules; and (3) whether the antioxidative action of quercetin protects the membrane against its modification. Our results show that changes in the stiffness/elasticity of the lipid part of the membrane constitute the decisive mechanism of action of quercetin, potentially influencing cellular processes whose initial stages are associated with membranes (e.g., reception of signals from the environment, transport).

Osmopriming, antioxidative action, and thermal stress in sunflower seeds with different vigor levels

The osmopriming technique can reduce the period between sowing and the emergence of seedlings in the field, as well as favor seed performance under stress conditions. This study aimed to evaluate the effect of osmopriming on the physiological performance and antioxidative enzymatic activity of sunflower seeds with different vigor levels and exposed to thermal stress. Three sunflower seed lots of the cultivar Hélio 250 were used. Initially, the seeds were evaluated by germination and vigor tests to characterize the lots. Subsequently, they were primed in a polyethylene glycol 6000 solution at -2.0 MPa and 15 °C for 8 h. Then, the primed and unprimed seeds were tested for physiological quality (germination, first germination count, percentage and emergence speed index of seedlings, and seedling dry matter) and determination of the activity of the enzymes superoxide dismutase (SOD), catalase (CAT), ascorbate peroxidase (APX), and peroxidase (POX) under three temperatures: 15 °C (sub-optimal), 25 °C (optimal), and 35 °C (supra-optimal). The physiological tests allowed classifying lots 1, 2, and 3 into three different vigor levels, i.e., high, medium, and low, respectively. Osmopriming favored the performance of sunflower seeds in terms of germination and vigor at all the analyzed temperatures. This effect was more pronounced in lots of lower physiological quality at sub-optimal and supra-optimal temperatures. Sub-and supra-optimal temperatures led to a reduction in the physiological performance of seeds, mainly in less vigorous lots. In general, osmopriming favored an increase in the activity of the enzymes SOD, CAT, POX, and APX, mainly in low vigor seeds exposed to sub and supra-optimal temperatures. Osmopriming of sunflower seeds in PEG 6000 at -2.0 MPa for 8 hours is efficient to improve the performance of less vigorous lots under stress due to the sub- and supra-optimal temperatures, favoring an increase in the activity of enzymes of the antioxidative system.

Minocycline Impact on Redox Homeostasis of Normal Human Melanocytes HEMn-LP Exposed to UVA Radiation and Hydrogen Peroxide

Minocycline is a semisynthetic tetracycline antibiotic. In addition to its antibacterial activity, minocycline shows many non-antibiotic, beneficial effects, including antioxidative action. The property is responsible, e.g., for anti-inflammatory, neuroprotective, and cardioprotective effects of the drug. However, long-term pharmacotherapy with minocycline may lead to hyperpigmentation of the skin. The reasons for the pigmentation disorders include the deposition of the drug and its metabolites in melanin-containing cells and the stimulation of melanogenesis. The adverse drug reaction raises a question about the influence of the drug on melanocyte homeostasis. The study aimed to assess the effect of minocycline on redox balance in human normal melanocytes HEMn-LP exposed to hydrogen peroxide and UVA radiation. The obtained results indicate that minocycline induced oxidative stress in epidermal human melanocytes. The drug inhibited cell proliferation, decreased the level of reduced thiols, and stimulated the activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). The described changes were accompanied by an increase in the intracellular level of ROS. On the other hand, pretreatment with minocycline at the same concentrations increased cell viability and significantly attenuated the oxidative stress in melanocytes exposed to hydrogen peroxide and UVA radiation. Moreover, the molecular docking analysis revealed that the different influence of minocycline and other tetracyclines on CAT activity can be related to the location of the binding site.

THERMODYNAMICALLY INVESTIGATIONS OF FREE RADICAL SCAVENGER POTENCY OF 1,2,4-TRIHYDROXYTHIOXANTHONE

The operative mechanism of the antioxidative action of 1,2,4-trihydroxythioxanthone (TX) is investigated in this contribution. Conclusions are made based on enthalpy values, as thermodynamical parameters. All calculations are done using the M06-2X/6-311++G(d,p) level of theory. To imitate polar and non-polar environments, calculations are done in water and benzene as the medium. It is found that, among three possible radicals that TX can generate, the most stable is the one obtained by homolytic cleavage of the O-H group in position 4. It was found that HAT (Hydrogen Atom Transfer) is the most plausible mechanism for that purpose in benzene. On the other hand, the most favorable mechanism in water is SPLET (Sequential Proton Loss Electron Transfer). Here is estimated the capacity of TX to deactivate hydroxyl (HO●), hydroperoxyl (HOO●) and methylperoxyl radical (CH3OO●). It is found that TX can deactivate all three free radicals following HAT and SPLET reaction mechanisms competitively, in the polar and non-polar environment. SET-PT (Single-Electron Transfer followed by Proton Transfer) is the inoperative mechanism for radicals scavenging, in the polar and non-polar environment.

Antioxidant of Trans-Resveratrol: A Comparison between OH and CH Groups Based on Thermodynamic Views

Trans-resveratrol establishes the planarity in its structure which makes it an interesting compound in both experimental and theoretical examinations. The current study, using the density functional method (DFT), attempts to compare the antioxidative capacities between hydroxyl (OH) and aromatic methine (CH) groups of this molecule. Becke’s exchange-correlation B3LYP functional together with 6-311++G(d, p) basis set was used to reveal the effects of structural geometry and electronic feature on the antioxidative results of OH and CH groups. The antioxidative action of trans-resveratrol has followed the HAT mechanism in gas, but the SPLET pathway in liquids. OH bond breaking is easier than CH bond disruption. 4-OH bond breaking induces the lowest BDE values of 74.4–77.9 kcal/mol in gas, acetone, methanol, and water, as well as the lowest PA values of 37.2–46.2 kcal/mol in acetone, methanol, and water. From the kinetic view, 4-OH is also an active center to capture laboratory radical DPPH, ROS radicals HOO• and CH3O•, and RNS radical •NO2.

(5-Hydroxy-4-oxo-2-styryl-4H-pyridin-1-yl)-acetic Acid Derivatives as Multifunctional Aldose Reductase Inhibitors

As rate-limited enzyme of polyol pathway, aldose reductase (ALR2) is one of the key inhibitory targets for alleviating diabetic complications. To reduce the toxic side effects of the inhibitors and to decrease the level of oxidative stress, the inhibitory selectivity towards ALR2 against detoxicating aldehyde reductase (ALR1) and antioxidant activity are included in the design of multifunctional ALR2 inhibitors. Hydroxypyridinone derivatives were designed, synthesized and evaluated their inhibitory behavior and antioxidant activity. Notably, {2-[2-(3,4-dihydroxy-phenyl)-vinyl]-5-hydroxy-4-oxo-4H-pyridin-1-yl}-acetic acid (7l) was the most potent, with IC50 values of 0.789 μM. Moreover, 7l showed excellent selectivity towards ALR2 with selectivity index 25.23, which was much higher than that of eparlestat (17.37), the positive control. More significantly, 7l performed powerful antioxidative action. At a concentration of 1 μM, phenolic compounds 7l scavenged DPPH radical with an inhibitory rate of 41.48%, which was much higher than that of the well-known antioxidant Trolox, at 11.89%. Besides, 7l remarkably suppressed lipid peroxidation with a rate of 88.76% at a concentration of 100 μM. The binding mode derived from molecular docking proved that the derivatives were tightly bound to the activate site, suggesting strongly inhibitory action of derivatives against ALR2. Therefore, these results provided an achievement of multifunctional ALR2 inhibitors capable with potency for both selective ALR2 inhibition and as antioxidants.

Antioxidative Action of Ellagic Acid—A Kinetic DFT Study

Although one can find numerous studies devoted to the investigation of antioxidative activity of ellagic acid (EA) in the scientific literature, the mechanisms of its action have not yet been fully clarified. Therefore, further kinetic studies are needed to understand its antioxidative capacity completely. This work aims to reveal the underlying molecular mechanisms responsible for the antioxidative action of EA. For this purpose, its reactions with HO• and CCl3OO• radicals were simulated at physiological conditions using the quantum mechanics-based test for overall free-radical scavenging activity. The density functional theory in combination with the conductor-like polarizable continuum solvation model was utilized. With HO• radical EA conforms to the hydrogen atom transfer and radical adduct formation mechanisms, whereas sequential proton loss electron transfer mechanism is responsible for scavenging of CCl3OO• radical. In addition, compared to trolox, EA was found more reactive toward HO•, but less reactive toward CCl3OO•. The calculated rate constants for the reactions of EA with both free radicals are in a very good agreement with the corresponding experimental values.