Mechanisms Of Antioxidant Action Research Articles

Low-Molecular-Weight Synthetic Antioxidants: Classification, Pharmacological Profile, Effectiveness and Trends.

Mounting research has been performed and published on natural antioxidants, more so than on synthetic ones, as key molecules that control oxidative damage and its pathway to disease. Since the discovery of vitamins, various fully synthetic or natural-identical compounds have been developed as stable small molecules translated into constantly active and completely controlled products which are widely exploited in the food and pharmaceutical industries. There is currently a debate within the literature about their mechanism of action, bioavailability, safety and real benefit for human health. Using a semiquantitative method and eligible criteria of selection, this review aimed to provide a very useful classification of antioxidants and a comprehensive cross-disciplinary description of 32 approved synthetic/natural-identical antioxidants, in terms of regulatory, antioxidant mechanism of action, safety issues, pharmacological properties, effectiveness in human health, timeline and future trends. Enriched interpretation of the data was obtained from summary bibliometrics, useful to portray the “good antioxidant” within the period 1966–2021 and, hopefully, to encourage further research.

Evaluating the Potential of Phytochemicals as Natural Substitute for Synthetic Antioxidant: A Review

This study aimed at investigating the antioxidant potential of flavonoids as a subgroup of polyphenols and ultimately entirely and partially substitute the synthetic antioxidant with natural them. All relevant databases were searched for the terms including 'phytochemical', polyphenol', 'flavonoid', 'natural additive', as well as 'antioxidant activity' combined with in vivo and in vitro phrases. Free radicals are among the damaging factors to macromolecules. The oxidative reaction caused by these radicals is one of the reasons for food spoilage, which causes unpleasant odor, loss of taste, damaged tissue and appearance, and loss of nutritional value of exposed material. The common antioxidants employed in foods include Butylated hydroxytoluene (BHT), Butylated hydroxyanisole (BHA), Tert-butyl hydroquinone (TBHQ), and Propyl gallate (P.G.). Synthetic antioxidants have adverse effects such as causing mutation and carcinogenicity in the human body despite their high performance; hence, many studies have been carried out on replacing them with natural antioxidants. Phytochemicals and a widespread group of them known as polyphenols possess a high antioxidant activity. A major subset of polyphenols, Flavonoids, are secondary metabolites in plants with many applications. These compounds are potential antioxidants because of their capabilities, such as scavenging the free radicals donating hydrogen atoms, electrons, and chelate metal cations. The antioxidant mechanism of action of flavonoids is transferring hydrogen toward free radicals. Accordingly, the more the flavonoid structure makes the hydrogen transfer faster and easier, the more the flavonoid's antioxidant power will be. Therefore, the antioxidant activity of the flavonoids with hydroxy groups in their structure is higher among the different flavonoids. Besides health promotion and some disease prevention effects, various in vitro studies have shown that flavonoids possess a high antioxidant activity that is competitive with synthetic antioxidants. However, to make it commercially available, cheaper and high-performance extraction methods of flavonoids will have to be developed.

TRANSDERMAL THERAPEUTIC SYSTEMS–AN INNOVATIVE METHOD TO PREVENT THE FORMATION OF KELOIDS

Modern medicine has achieved significant results in the development of techniques to avoid surgeries. However, surgical methods are still one of the main tools for treating pathologies in the human body. Plastic surgery and cosmetology are gaining popularity every year, and sports injuries require the use of combined treatment methods, but any such intervention leads to the risk of keloids. The younger the person, the higher the likelihood of developing a keloid, due to the high degree of elasticity of the skin at an earlier age, which is prone to scarring than in older people. Women are at higher risk of developing keloids than men because their skin is more elastic. Thus, children and young women are most at risk of keloid formation, both as a result of physiological processes of skin scarring and preference for plastic surgery, cosmetic procedures and other methods of correction. In world pharmaceutical practice, there are not enough existing ways to prevent the development of keloid. It is necessary to conduct research on the selection of a fundamentally new structural basis for a transdermal therapeutic system containing the most effective and safe compounds of the regenerating and antioxidant mechanisms of action (vitamins and other biologically active compounds) from the point of view of preventing the formation of keloids, which will help in solving the problem of not only preventing the formation of keloids in the dermis, but also its subsequent growth and exit to the surface layers of the skin.

Oxidative Stress, Cancer and Antioxidant: A symbiosis?

The imbalance production of free radicals and reactive metabolites known as reactive oxygen species (ROS) and their elimination, will developed oxidative stress. ROS are playing dual roles as deleterious or beneficial species. At low level, they act as messengers in cell signaling and play a role in maintaining homeostasis whereas at higher concentration will cause cellular redox imbalance. This event is commonly occurred in cancer cells compared to normal cells. The oxidative DNA damage occurs as a result of elevated level of ROS causing single or double strand DNA breaks, replication errors, base modification, base oxidation, DNA cross-linking which leads to cell dysfunction and cell death. Taking antioxidant such as polyphenolic compounds is believed to exert anticancer effect due to ROS manifestations. Studies with flavonoids compounds exerted anticancer activity through modulation of ROS-scavenging enzyme activities, cell cycle arrest, induction of apoptosis, autophagy, and suppression of cancer cell proliferation and invasiveness. However, the mechanisms responsible for this anticancer effect have not been fully understood. Most of the laboratory and animal studies exhibited increased levels of exogenous antioxidants which prevent the types of free radical damage associated with cancer development. Few clinical studies in human were conducted with aim to observe possibilities of lowering risk of developing or dying from cancer upon taking dietary supplements. The dietary antioxidant supplements which were tested on human subjects were beta carotene, tocopherol, alpha tocopherol, vitamin C, selenium and zinc. These studies have yielded mixed results. In some preclinical studies, antioxidants have been found to promote tumor growth and metastasize. In tumor-bearing mice the supplements given had increased the ability to circulate tumor cells to metastasize. In conclusion, the mechanism of antioxidant action in cancer treatment is poorly understood. Many factors need to be considered before taking or giving antioxidant supplement since there were reports pertaining to benefits and disadvantages of antioxidant in cancer treatment.

Curcumin-based ionic Pt(II) complexes: antioxidant and antimicrobial activity.

A series of novel cationic curcumin-based Pt(II) complexes with neutral (N^N) ligands and triflate anions as counterions, [(N^N)Pt(curc)]CF3SO3, 1-4, were synthesised and fully characterised. The antioxidant radical scavenging activity of complexes 1-4 was measured spectrophotometrically using DPPH as the internal probe. Computational strategies have been exploited to ascertain the mechanism of antioxidant action of curcumin (H(curc)) and its Pt(II) complexes. Finally, compounds 1-4 were tested in vitro for their growth inhibitory activity against two bacteria (Staphylococcus aureus and Escherichia coli) by the disk diffusion technique at different Pt(II) complex solution concentrations. The effect of the complexation of H(curc) was investigated.

Emodin Attenuates the ECM Degradation and Oxidative Stress of Chondrocytes through the Nrf2/NQO1/HO‐1 Pathway to Ameliorate Rat Osteoarthritis

Osteoarthritis (OA) substantially reduces the quality of life of the elderly. OA therapy remains a challenge since no treatment options for its causes are so far available. Over recent years, researchers have speculated that emodin may represent a potential treatment strategy for OA. However, it remains unclear whether the mechanism of action of emodin is associated with the inhibition of OA‐induced oxidative stress. In the present study, the potential antioxidant mechanism of action of emodin and its protective properties against the development of OA were investigated both in vitro and in vivo. In vitro, emodin inhibited the production of reactive oxygen species (ROS) in chondrocytes induced by hydrogen peroxide (H2O2) and reduced the expression of matrix metalloproteinase (MMP)3 and MMP13 in a concentration‐dependent manner. It was found that emodin upregulated the Nrf2/NQO1/HO‐1 pathway, thereby attenuating the effects of oxidative stress caused by OA. In a rat model of posttraumatic OA induced by anterior cruciate ligament transection (ACLT), emodin reduced the extent of joint swelling. Emodin attenuated oxidative damage in the cartilage by upregulating superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) activity, reducing malondialdehyde (MDA) concentration and inhibiting the expression of the extracellular matrix (ECM) degradation biomarkers cartilage oligomeric matrix protein (COMP), and C‐terminal telopeptide of type I collagen (CTX‐I) and type II collagen (CTX‐II), thereby reducing cartilage damage. In summary, the present study indicates that emodin reduces ECM degradation and oxidative stress in chondrocytes via the Nrf2/NQO1/HO‐1 pathway, thereby ameliorating OA in rats.

Resveratrol ameliorates necrotizing enterocolitis in neonatal rats through regulation of inflammatory and apoptotic pathways

Purpose: To determine the efficacy of resveratrol in mitigating necrotizing enterocolitis (NEC) in neonatal rats.Methods: Necrotizing enterocolitis (NEC) was induced in neonatal rats using hypoxia and hypothermia. At the completion of treatment, the intestinal tissues of the rats were isolated for evaluation of various biochemical parameters.Results: There was significant increase in the levels of proinflammatory cytokines (TNF-α, IL-6 and IL-1β) and oxidative stress markers (MDA, xanthine oxidase and nitric oxide) in intestinal tissues of NEC rats (p < 0.05). However, resveratrol treatment led to significant decrease in the levels of cytokines and oxidative stress parameters, relative to the NEC group (p < 0.05). Furthermore, Western blotting resultsshowed up-regulation in protein expressions of inflammatory cytokines in NEC rats. However, the protein expressions of inflammatory cytokines were down-regulated in the NEC rats on treatment with resveratrol. Moreover, resveratrol reversed the NEC-induced up-regulations of Bax and caspase-3, as well as NEC-mediated down-regulation of Bcl-2.Conclusion: These results demonstrate that resveratrol mitigates NEC-induced intestinal damage in neonatal rats via anti-inflammatory, anti-apoptotic and antioxidant mechanisms of action. Therefore, resveratrol is a potential therapeutic agent for NEC.

Kinetics and mechanism of antioxidant action of triterpenoids in the liquid-phase oxidation reaction of 1,4-dioxane

Kinetics and mechanism of antioxidant action of triterpenoids in the liquid-phase oxidation reaction of 1,4-dioxane

Design and Antioxidant Properties of Bifunctional 2H-Imidazole-Derived Phenolic Compounds-A New Family of Effective Inhibitors for Oxidative Stress-Associated Destructive Processes.

The synthesis of inhibitors for oxidative stress-associated destructive processes based on 2H-imidazole-derived phenolic compounds affording the bifunctional 2H-imidazole-derived phenolic compounds in good-to-excellent yields was reported. In particular, a series of bifunctional organic molecules of the 5-aryl-2H-imidazole family of various architectures bearing both electron-donating and electron-withdrawing substituents in the aryl fragment along with the different arrangements of the hydroxy groups in the polyphenol moiety, namely derivatives of phloroglucinol, pyrogallol, hydroxyquinol, including previously unknown water-soluble molecules, were studied. The structural and antioxidant properties of these bifunctional 5-aryl-2H-imidazoles were comprehensively studied. The redox transformations of the synthesized compounds were carried out. The integrated approach based on single and mixed mechanisms of antioxidant action, namely the AOC, ARC, Folin, and DPPH assays, were applied to estimate antioxidant activities. The relationship “structure-antioxidant properties” was established for each of the antioxidant action mechanisms. The conjugation effect was shown to result in a decrease in the mobility of the hydrogen atom, thus complicating the process of electron transfer in nearly all cases. On the contrary, the conjugation in imidazolyl substituted phloroglucinols was found to enhance their activity through the hydrogen transfer mechanism. Imidazole-derived polyphenolic compounds bearing the most electron-withdrawing functionality, namely the nitro group, were established to possess the higher values for both antioxidant and antiradical capacities. It was demonstrated that in the case of phloroglucinol derivatives, the conjugation effect resulted in a significant increase in the antiradical capacity (ARC) for a whole family of the considered 2H-imidazole-derived phenolic compounds in comparison with the corresponding unsubstituted phenols. Particularly, conjugation of the polyphenolic subunit with 2,2-dimethyl-5-(4-nitrophenyl)-2H-imidazol-4-yl fragment was shown to increase ARC from 2.26 to 5.16 (104 mol-eq/L). This means that the considered family of compounds is capable of exhibiting an antioxidant activity via transferring a hydrogen atom, exceeding the activity of known natural polyphenolic compounds.

A Simple Route to the Complexation of Lutein with Reduced Graphene Oxide Nanocarriers and Antioxidant Protection Against Blue Light.

BackgroundThe excellent physicochemical properties of graphene-based materials, including graphene oxide (GO) and reduced GO (rGO), offer significant technological potential as multifunctional nanomaterials in biomedical fields. Lutein is a type of carotenoid that forms human macular pigments in the retina, where it inhibits harmful blue light and contributes to the strengthening of the antioxidant defense of retinal pigment epithelium cells.MethodsSynthesis of the Lutein-rGO (Lu–rGO) complex was carried out for the optimized concentration. Then characterization of material was analyzed through ultraviolet-visible spectrophotometer (UV-Vis spectra), Fourier-transform infrared spectroscopy (FT-IR), Raman spectroscopy, x-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM). Antioxidant activity of Lu–rGO complex was measured by 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2.2-diphenyl-1-picrylhydrazyl (DPPH), glutathione (GSH) oxidation assay. Then, oxidative stress induction by blue light and analyzed intracellular reactive oxygen species (ROS).Results and ConclusionBased on the FT-IR measurement, the reduction efficiency defined by area was found to be 87.3%, the ID/IG ratio of 0.98 demonstrated by the Lu–rGO complex in the Raman spectrum was slightly higher than that of the original GO. The exhibited significant decrease in the peak intensities of the oxygen functional groups of the XPS spectra of the Lu–rGO complex was observed compared with the GO. In the TEM image for the Lu–rGO complex, folded and wrinkled nanostructures over the lutein-covered rGO surface were evidenced by tight molecular binding. The Lu–rGO complex provided superior DPPH and ABTS radical scavenging activity than GO and lutein alone, and the oxidation of GSH was suppressed. It was confirmed that the content of intracellular ROS and lysosomes, increased by blue light, was reduced after treatment with the Lu–rGO complex on ARPE-19 cells. In summary, graphene-based nanocarriers could function as preventative antioxidants during photochemical ROS generation based on the mechanism of antioxidant action.

NPCdc, a synthetic natriuretic peptide, is a substrate to neprilysin and enhances blood pressure-lowering induced by enalapril in 5/6 nephrectomized rats

NPCdc is a natriuretic peptide synthesized from the amino acid sequence of the Crotalus durissus cascavella snake venom peptide, NP2Casca. NPCdc presents hypotensive and antioxidants effects. This study aimed to investigate in vivo whether angiotensin I-converting enzyme (ACE) inhibition would influence the impact of NPCdc in arterial pressure of rats submitted to 5/6 nephrectomy (Nx). Adult male Wistar rats following a 5/6 Nx were treated with enalapril (NxE group, 10 mg/kg/day, n = 9) or vehicle (Nx group, n = 8) for two weeks. On the 15th day after Nx, rats were anaesthetized and submitted to mean arterial pressure (MAP) determination before and after receiving two intravenous injections of saline (vehicle, n = 9) or NPCdc (0.3 μg/kg dissolved in saline, n = 18) separated by a 20-min interval. The kidneys were submitted to oxidative stress analysis. The basal MAP of the NxE group was nearly 20% lower (P < 0.05) than non-treated rats. NPCdc administration decreased the MAP in both groups; however, in the NxE group, the effects were observed only in the second injection. The peptide also decreased the NADPH oxidase activity in the renal cortex. Additionally, the hydrolysis of NPCdc by recombinant neprilysin (NEP) was monitored by mass spectrometry. NPCdc was cleaved by NEP at different peptides with an inhibition constant (Ki) of 1.5 μM, determined by a competitive assay using the NEP fluorescence resonance energy transfer (FRET) peptide substrate Abz-(d)Arg-Gly-Leu-EDDnp. Docking experiments confirmed the high affinity of NPCdc toward NEP. These findings provide new insights into the antihypertensive and antioxidant mechanism of action of NPCdc. Altogether, the results presented here suggest that NPCdc must be further studied as a potential therapy for cardiorenal syndromes.

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.

Mechanisms of Antioxidant Actions and their Role in many Human Diseases: A Review

Mechanisms of Antioxidant Actions and their Role in many Human Diseases: A Review

Insights into the Antioxidant Mechanism of Newly Synthesized Benzoxazinic Nitrones: In Vitro and In Silico Studies with DPPH Model Radical.

Synthetic nitrone spin-traps are being explored as therapeutic agents for the treatment of a wide range of oxidative stress-related pathologies, including but not limited to stroke, cancer, cardiovascular, and neurodegenerative diseases. In this context, increasing efforts are currently being made to the design and synthesis of new nitrone-based compounds with enhanced efficacy. The most researched nitrones are surely the ones related to α-phenyl-tert-butylnitrone (PBN) and 5,5-dimethyl-1-pyrroline N-oxide (DMPO) derivatives, which have shown to possess potent biological activity in many experimental animal models. However, more recently, nitrones with a benzoxazinic structure (3-aryl-2H-benzo[1,4]oxazin-N-oxides) have been demonstrated to have superior antioxidant activity compared to PBN. In this study, two new benzoxazinic nitrones bearing an electron-withdrawing methoxycarbonyl group on the benzo moiety (in para and meta positions respect to the nitronyl function) were synthesized. Their in vitro antioxidant activity was evaluated by two cellular-based assays (inhibition of AAPH-induced human erythrocyte hemolysis and cell death in human retinal pigmented epithelium (ARPE-19) cells) and a chemical approach by means of the α,α-diphenyl-β-picrylhydrazyl (DPPH) scavenging assay, using both electron paramagnetic resonance (EPR) spectroscopy and UV spectrophotometry. A computational approach was also used to investigate their potential primary mechanism of antioxidant action, as well as to rationalize the effect of functionalization on the nitrones reactivity toward DPPH, chosen as model radical in this study. Further insights were also gathered by exploring the nitrone electrochemical properties via cyclic voltammetry and by studying their kinetic behavior by means of EPR spectroscopy. Results showed that the introduction of an electron-withdrawing group in the phenyl moiety in the para position significantly increased the antioxidant capacity of benzoxazinic nitrones both in cell and cell-free systems. From the mechanistic point of view, the calculated results closely matched the experimental findings, strongly suggesting that the H-atom transfer (HAT) is likely to be the primary mechanism in the DPPH quenching.

In vitro and in silico studies of radical scavenging activity of salicylaldehyde benzoylhydrazones

Hydrazones are key compounds for drug design and popular building blocks in the development of functional materials because of their simple structure, straightforward synthesis, hydrolytic stability, tendency toward crystallinity and tunable properties, etc. Hydrazones have been under study for a long time, but many of their electronic and structural properties (that can be attributed to the basic system structure) remain unexplored. In this paper the effect of substitution is studied for a set of selected aroylhydrazones – derivatives of the active chelator salicylaldehyde benzoyl hydrazone (SBH). The molecular structure of the compounds in nonpolar and polar media was characterized by DFT computations and vibrational (ATR-FTIR and Raman) spectroscopy. The radical scavenging ability of the compounds was tested towards stable free radicals as well as for inhibiting the iron induced oxidative stress in a lecithin containing model system. The possible mechanisms of antioxidant action were evaluated by DFT calculations in polar and nonpolar media. The most reactive sites for hydrogen atom abstraction and proton transfer were determined based on the calculated enthalpies required for the formation of hydroxyl and amide radicals and ionic species. The structural parameters and thermodynamic data for the studied compounds were correlated with the observed effects in the in vitro model systems in order to rationalize the influence of the nature and position of the substituent in the phenyl ring on the antioxidant properties.

Crystal Structure, Spectroscopic Characterization, Antioxidant and Cytotoxic Activity of New Mg(II) and Mn(II)/Na(I) Complexes of Isoferulic Acid.

The Mg(II) and heterometallic Mn(II)/Na(I) complexes of isoferulic acid (3-hydroxy-4-methoxycinnamic acid, IFA) were synthesized and characterized by infrared spectroscopy FT-IR, FT-Raman, electronic absorption spectroscopy UV/VIS, and single-crystal X-ray diffraction. The reaction of MgCl2 with isoferulic acid in the aqueous solutions of NaOH resulted in synthesis of the complex salt of the general formula of [Mg(H2O)6]⋅(C10H9O4)2⋅6H2O. The crystal structure of this compound consists of discrete octahedral [Mg(H2O)6]2+ cations, isoferulic acid anions and solvent water molecules. The hydrated metal cations are arranged among the organic layers. The multiple hydrogen-bonding interactions established between the coordinated and lattice water molecules and the functional groups of the ligand stabilize the 3D architecture of the crystal. The use of MnCl2 instead of MgCl2 led to the formation of the Mn(II)/Na(I) complex of the general formula [Mn3Na2(C10H7O4)8(H2O)8]. The compound is a 3D coordination polymer composed of centrosymmetric pentanuclear subunits. The antioxidant activity of these compounds was evaluated by assays based on different antioxidant mechanisms of action, i.e., with •OH, DPPH• and ABTS•+ radicals as well as CUPRAC (cupric ions reducing power) and lipid peroxidation inhibition assays. The pro-oxidant property of compounds was measured as the rate of oxidation of Trolox. The Mg(II) and Mn(II)/Na(I) complexes with isoferulic acid showed higher antioxidant activity than ligand alone in DPPH (IFA, IC50 = 365.27 μM, Mg(II) IFA IC50 = 153.50 μM, Mn(II)/Na(I) IFA IC50 = 149.00 μM) and CUPRAC assays (IFA 40.92 μM of Trolox, Mg(II) IFA 87.93 μM and Mn(II)/Na(I) IFA 105.85 μM of Trolox; for compounds’ concentration 10 μM). Mg(II) IFA is a better scavenger of •OH than IFA and Mn(II)/Na(I) IFA complex. There was no distinct difference in ABTS•+ and lipid peroxidation assays between isoferulic acid and its Mg(II) complex, while Mn(II)/Na(I) complex showed lower activity than these compounds. The tested complexes displayed only slight antiproliferative activity tested in HaCaT human immortalized keratinocyte cell line within the solubility range. The Mn(II)/Na(I) IFA (16 μM in medium) caused an 87% (±5%) decrease in cell viability, the Mg salt caused a comparable, i.e., 87% (±4%) viability decrease in a concentration of 45 μM, while IFA caused this level of cell activity attenuation (87% ± 5%) at the concentration of 1582 μM (significant at α = 0.05).

Propolis Extract and Its Bioactive Compounds-From Traditional to Modern Extraction Technologies.

Propolis is a honeybee product known for its antioxidant, anti-inflammatory, anticancer, and antimicrobial effects. It is rich in bioactive molecules whose content varies depending on the botanical and geographical origin of propolis. These bioactive molecules have been studied individually and as a part of propolis extracts, as they can be used as representative markers for propolis standardization. Here, we compare the pharmacological effects of representative polyphenols and whole propolis extracts. Based on the literature data, polyphenols and extracts act by suppressing similar targets, from pro-inflammatory TNF/NF-κB to the pro-proliferative MAPK/ERK pathway. In addition, they activate similar antioxidant mechanisms of action, like Nrf2-ARE intracellular antioxidant pathway, and they all have antimicrobial activity. These similarities do not imply that we should attribute the action of propolis solely to the most representative compounds. Moreover, its pharmacological effects will depend on the efficacy of these compounds’ extraction. Thus, we also give an overview of different propolis extraction technologies, from traditional to modern ones, which are environmentally friendlier. These technologies belong to an open research area that needs further effective solutions in terms of well-standardized liquid and solid extracts, which would be reliable in their pharmacological effects, environmentally friendly, and sustainable for production.

Molecular regulation of lung maturation in near-term fetal sheep by maternal daily vitamin C treatment in late gestation

BackgroundIn the fetus, the appropriate balance of prooxidants and antioxidants is essential to negate the detrimental effects of oxidative stress on lung maturation. Antioxidants improve respiratory function in postnatal life and adulthood. However, the outcomes and biological mechanisms of antioxidant action in the fetal lung are unknown.MethodsWe investigated the effect of maternal daily vitamin C treatment (200 mg/kg, intravenously) for a month in late gestation (105–138 days gestation, term ~145 days) on molecular regulation of fetal lung maturation in sheep. Expression of genes and proteins regulating lung development was quantified in fetal lung tissue. The number of surfactant-producing cells was determined by immunohistochemistry.ResultsMaternal vitamin C treatment increased fetal lung gene expression of the antioxidant enzyme SOD-1, hypoxia signaling genes (HIF-2α, HIF-3α, ADM, and EGLN-3), genes regulating sodium movement (SCNN1-A, SCNN1-B, ATP1-A1, and ATP1-B1), surfactant maturation (SFTP-B and ABCA3), and airway remodeling (ELN). There was no effect of maternal vitamin C treatment on the expression of protein markers evaluated or on the number of surfactant protein-producing cells in fetal lung tissue.ConclusionsMaternal vitamin C treatment in the last third of pregnancy in sheep acts at the molecular level to increase the expression of genes that are important for fetal lung maturation in a healthy pregnancy.ImpactMaternal daily vitamin C treatment for a month in late gestation in sheep increases the expression of gene-regulating pathways that are essential for normal fetal lung development.Following late gestation vitamin C exposure in a healthy pregnancy, an increase in lung gene but not protein expression may act as a mechanism to aid in the preparation for exposure to the air-breathing environment after birth.In the future, the availability/development of compounds with greater antioxidant properties than vitamin C or more specific targets at the site of oxidative stress in vivo may translate clinically to improve respiratory outcomes in complicated pregnancies at birth.

The effects of recombinant klotho in cisplatin-induced ovarian failure in mice.

To investigate whether recombinant klotho given concomitantly with cisplatin is effective in preventing cisplatin-induced ovarian damage. Thirty-two adult female mice were divided into four groups. Saline was given to the first group, cisplatin to the second group, recombinant mouse klotho to the third group, and recombinant mouse klotho + cisplatin to the fourth group. The removed ovarian tissues were examined and groups were compared histologically and immunohistochemical examination for antimullerian hormone (AMH), superoxide dismutase (SOD) and catalase expression were done. Glutathione peroxidase (GPx) and glutathione reductase (GR) activities were measured by ELISA. Ovarian tissue weight, primary and secondary follicle counts were higher in cisplatin + recombinant klotho group compared to cisplatin group in our study (respectively p < 0.0001, p < 0.0001, and p = 0.010). Injury scores (stromal congestion, edema and infiltration, follicular degeneration scores and edema in corpus luteum scores) were similar between cisplatin and cisplatin + recombinant klotho groups (all p > 0.05). AMH staining intensities were similar between cisplatin and cisplatin + recombinant klotho groups (p = 0.925). There was no difference between the groups in terms of SOD, GPx, and GR (p > 0.05). The recombinant klotho administered before cisplatin could partially protect the ovarian tissue from cisplatin-induced ovarian damage considering that there was no difference in histologic injury score parameters, AMH staining intensity and oxidative stress markers between cisplatin and cisplatin plus klotho groups except that klotho preserved follicules to some extent. The antioxidant mechanism of action of klotho may not be the primary protection mechanism in cisplatin induced ovarian injury.