Mechanisms Of Antioxidant Action Research Articles

Bone Marrow Mesenchymal Stem Cells-Derived Exosomes Promote Survival of Random Flaps in Rats through NRF2-Mediated Antioxidative Stress.

Random flaps are the most used defect repair method for head and neck tumors and trauma plastic surgery. The distal part of the flap often undergoes oxidative stress (OS), ultimately leading to flap necrosis. Stem cells exosomes exhibit potential effects related to anti-inflammatory, regenerative, and antioxidant properties. Nuclear factor erythroid-2-related factor 2 (Nrf2) is an important factor in regulating oxidative balance. Exosomes have been reported to monitor its transcription to alleviate OS. This study examined the impacts and underlying mechanisms of antioxidant actions of exosomes derived from bone marrow mesenchymal stem cells (BMSCs-Exo) on random flaps. BMSCs-Exo was injected into the tail veins of rats on days 0, 1, and 2 after surgery of random flaps. The rats were euthanized on day 3 to calculate the survival rate. Immunohistochemical staining, western blotting, dihydroethidium probe, superoxide dismutase, and malondialdehyde assay kits were used to detect OS level. Human umbilical vein endothelial cells were co-cultured with BMSCs-Exo and ML385 (an inhibitor of Nrf2) in vitro. BMSCs-Exo may significantly improve the survival rate of the random flaps by reducing apoptosis, inflammation, and OS while increasing angiogenesis. Besides, BMSCs-Exo can also increase mitochondrial membrane potential and reduce reactive oxygen species levels in vitro. These therapeutic effects might stem from the activation of the Keap1/Nrf2 signaling pathway. BMSCs-Exo improved the tissue antioxidant capacity by regulating the keap1/Nrf2 signaling pathway. BMSCs-Exo may be a new strategy to solve the problem of random flap necrosis.

Mechanism of Antiradical Activity of Coumarin-Trihydroxybenzohydrazide Derivatives: A Comprehensive Kinetic DFT Study.

As part of this study, the mechanisms of the antioxidant activity of previously synthesized coumarin-trihydrobenzohydrazine derivatives were investigated: (E)-2,4-dioxo-3-(1-(2-(2″,3″,4″-trihydroxybenzoyl)hydrazineyl)ethylidene)chroman-7-yl acetate (1) and (E)-2,4-dioxo-3-(1-(2-(3″,4″,5″-trihydroxybenzoyl)hydrazineyl)ethylidene)chroman-7-yl acetate (2). The capacity of the compounds to neutralize HO• was assessed by EPR spectroscopy. The standard mechanisms of antioxidant action, Hydrogen Atom Transfer (HAT), Sequential Proton Loss followed by Electron Transfer (SPLET), Single-Electron Transfer followed by Proton Transfer (SET-PT), and Radical Adduct/Coupling Formation (RAF/RCF) were examined using the QM-ORSA methodology. It was estimated that the newly synthesized compounds, under physiological conditions, exhibited antiradical activity via SPLET and RCF mechanisms. Based on the estimated overall rate constants (koverall), it can be concluded that 2 exhibited a greater antiradical capacity. The obtained values indicated a good correlation with the EPR spectroscopy results. Both compounds exhibit approximately 1.5 times more activity in comparison to the precursor compound used in the synthesis (gallic acid).

Exploring the antioxidant stability of sheep bone protein hydrolysate -identification and molecular docking

The aim of this study was to obtain sheep bone protein hydrolysates (SBPHs) with antioxidant activity from sheep bone byproducts and evaluate their stability and processing characteristics under different conditions. Then, the antioxidant peptides were identified and synthesized, and their antioxidant mechanism of action was investigated using molecular docking. The results showed that SBPHs obtained by alkaline protease hydrolysis had high antioxidant capacity and a high proportion of hydrophobic amino acids (41.33%). The antioxidant activity of SBPHs was intolerant to high temperatures and weakly resistant to acids and alkalis. NaCl improved the reducing power, sugars maintained the antioxidant activity, and metal ions reduced the antioxidant activity of SBPHs. SBPHs maintained higher antioxidant activity after simulated gastrointestinal digestion. Three fractions were isolated by ultrafiltration, among which P–I (MW < 3 kDa) had the strongest antioxidant activity. Liquid chromatography–tandem mass spectrometry (LC‒MS/MS) showed that 17 peptides with Peptide Ranker >0.85 were found in P–I. Among the synthesized peptides, VYPFPGPIPN had the strongest antioxidant activity, which was mainly exerted through hydrogen bonding, π-π stacking and π-alkyl bonding with Keap1. This study provides a reference for subsequent studies on the production, storage and antioxidant function utilization of SBPHs.

Evaluation of the Antioxidant Properties and Cytotoxic Activity of 1,3-dioxolane Derivatives Imidazole

Introduction. Modern chemotherapy widely considers the role of antioxidant and pro-oxidant methods in the treatment of oncologic pathologies. The use of agents that cause an increase of ROS is a relevant way to destroy tumors. At the same time, there is evidence of the ability of some antioxidants to lead to the cancer cells apoptosis through the generation of free radical forms of oxygen due to disruption of cellular homeostasis. The combination of the «Ecolum» biosensor using technique, antiradical activity data, and information about the cytotoxicity of compounds used in the study allows us to consistently conduct low-cost screening of as antioxidant, as antiradical activities and potentially reduce the required number of expensive cytotoxicity determinations using tumor cells.Aim. The main target of our work is the evaluation of antioxidant and cytotoxic activities of 1,3-dioxolane derivatives of imidazole using antioxidant, antiradical and cytotoxicity tests in vitro.Materials and methods. To carry out this study, 1,3-dioxolane derivatives of imidazole were obtained. The antiradical tests was performed using the DPPH (2,2-diphenyl-1-picrylhydrazyl) method. Antioxidant properties were assessed within the Ecolum biosensor in the state of oxidative stress. Cytotoxic activity was assessed in GIST-T1 cell culture using the MTT test (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide).Results and discussion. Data from studies of the antioxidant activity of substances using the «Ecolum» biosensor showed varying degrees of damage to the biosensor in the absence of antioxidant action. The antiradical potential, initially used to reveal a possible mechanism of antioxidant action, actually demonstrated a possible mechanism of toxic action of substance 2c due to its antiradical effect comparable to the standard (Trolox), but the substance has the highest cytotoxicity. However, the properties of substance 2a shows that the direct correlation discussed earlier is not found in all cases.Conclusion. The asessment of the antioxidant properties and cytotoxic activity of 1,3-dioxolane derivatives of imidazole demonstrated the relevance of further searching for connections between the results of substances binding with the Ecolum biosensor under conditions of oxidative stress, their antiradical potential and cytotoxic properties. This combination of tests will potentially reduce the cost of screening through the use of an available biosensor, establish a possible mechanism of action aimed at redox balance, and confirm previously obtained data through the use of tumor cell culture.

Structural Study of a La(III) Complex of a 1,2,3-Triazole Ligand with Antioxidant Activity.

The 1,2,3-triazole derivative 2-(4-chlorophenyl)-5-(pyrrolidin-1-yl)-2H-1,2,3-triazole-4-carboxylic acid with potential anticancer activity was used as a ligand in complex formation with the lanthanum(III) ion. The molecular structure and vibrational spectra of the complex were optimized at three DFT levels, and the scaled IR and Raman spectra were compared to the experimental ones. Several scaling procedures were used. Through a detailed analysis, the structure predicted for the newly synthetized La(III) complex was confirmed by the good accordance of the calculated/experimental IR and Raman spectra. The best DFT method appeared to be M06-2X with the Lanl2mb basis set, followed closely by Lanl2dz. The effect of the lanthanide atom on the molecular structure and atomic charge distribution of the triazole ring was evaluated. The potential free radical scavenging activity of both the ligand and the complex was investigated in several radical-generating model systems. The potential mechanisms of antioxidant action (hydrogen atom transfer (HAT) and single-electron transfer (SET)) were elucidated.

Inhibitory effects and action mechanism of five antioxidant peptides derived from wheat gluten on cells oxidative stress injury

Our previous study identified five peptides Leu-Tyr (LY), Pro-Tyr (PY), Tyr-Gln (YQ), Ala-Pro-Ser-Tyr (APSY), and Arg-Gly-Gly-Tyr (RGGY) from wheat gluten. However, the mechanism of antioxidant action and structure-function relationship of these five peptides were still unclear. In this study, we found that five peptides induced by AAPH in human embryonic kidney cells (HEK-293) suppressed the intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) production. Moreover, they also upregulated the antioxidant activity-related enzymes (SOD, CAT and GSH-Px) and GSH activities. Additionally, five peptides treatment decreased Keap1 protein level and increased Nrf2 and HO-1proteins levels. It was concluded that five peptides showed promise in activating the Keap1-Nrf2-HO-1 signaling pathway and enhancing the antioxidant defense system. Quantum chemical calculation and molecular docking technologies were used to explore the action mechanism of five wheat peptides. Five antioxidant peptides were able to effectively bind Keap1, and the peptides predominantly formed hydrogen and π bonds during their binding with the active pocket region of Keap1.

Oxidative Damage as a Fundament of Systemic Toxicities Induced by Cisplatin-The Crucial Limitation or Potential Therapeutic Target?

Cisplatin, an inorganic complex of platinum, is a chemotherapeutic drug that has been used for 45 years. Despite the progress of pharmaceutical sciences and medicine and the successful application of other platinum complexes for the same purpose, cisplatin is still the therapy of choice in many cancers. Treatment for testicular, ovarian, head and neck, urothelial, cervical, esophageal, breast, and pulmonary malignancies is still unthinkable without the use of this drug. However, cisplatin is also known for many side effects, of which the most pronounced are nephrotoxicity leading to acute renal failure, neurotoxicity, and ototoxicity. Mechanistic studies have proven that one of the conditions that plays a major role in the development of cisplatin-induced toxicities is oxidative stress. Knowing the fact that numerous antioxidants can be used to reduce oxidative stress, thereby reducing tissue lesions, organ failure, and apoptosis at the cellular level, many studies have defined antioxidants as a priority for investigation as a cotreatment. To investigate the mechanism of antioxidant action in vivo, many animal models have been employed. In the last few years, studies have mostly used rodents and zebrafish models. In this article, some of the most recent investigations that used animal models are listed, and the advantages and disadvantages of such experimental studies are pointed out.

Understanding mechanisms of antioxidant action in health and disease.

Several different reactive oxygen species (ROS) are generated in vivo. They have roles in the development of certain human diseases whilst also performing physiological functions. ROS are counterbalanced by an antioxidant defence network, which functions to modulate ROS levels to allow their physiological roles whilst minimizing the oxidative damage they cause that can contribute to disease development. This Review describes the mechanisms of action of antioxidants synthesized in vivo, antioxidants derived from the human diet and synthetic antioxidants developed as therapeutic agents, with a focus on the gaps in our current knowledge and the approaches needed to close them. The Review also explores the reasons behind the successes and failures of antioxidants in treating or preventing human disease. Antioxidants may have special roles in the gastrointestinal tract, and many lifestyle features known to promote health (especially diet, exercise and the control of blood glucose and cholesterol levels) may be acting, at least in part, by antioxidant mechanisms. Certain reactive sulfur species may be important antioxidants but more accurate determinations of their concentrations in vivo are needed to help assess their contributions.

Metformin mitigates radiation toxicity exerting antioxidant and genoprotective properties.

The antidiabetic drug metformin (MF) exhibits redox-modulating effects in various pathologies associated with oxidative stress and mitigates ionizing radiation-induced toxicity, but the underlying mechanisms remain to be elucidated. Thus, we studied some radiomitigatory effects of MF and explored the possible mechanisms behind them. Highly sensitive luminescence methods and non-competitive enzyme-linked immunosorbent assay (ELISA) were used in in vitro studies, and in vivo the damage to bone marrow cells and its repair were assessed by the micronucleus test. In a solution, MF at concentrations exceeding 0.1µM effectively intercepts •OH upon X-ray-irradiation, but does not react directly with H2O2. MF accelerates the decomposition of H2O2 catalyzed by copper ions. MF does not affect the radiation-induced formation of H2O2 in the solution of bovine gamma-globulin (BGG), but has a modulating effect on the generation of H2O2 in the solution of bovine serum albumin (BSA). MF at 0.05-1mM decreases the radiation-induced formation of 8-oxoguanine in a DNA solution depending on the concentration of MF with a maximum at 0.25mM. MF at doses of 3mg/kg body weight (bw) and 30mg/kg bw administered to mice after irradiation, but not before irradiation, reduces the frequency of micronucleus formation in polychromatophilic erythrocytes of mouse red bone marrow. Our work has shown that the radiomitigatory properties of MF are mediated by antioxidant mechanisms of action, possibly including its ability to chelate polyvalent metal ions.

Electrochemical Characterization of the Antioxidant Properties of Medicinal Plants and Products: A Review

Medicinal plants are an important source of bioactive compounds with a wide spectrum of practically useful properties. Various types of antioxidants synthesized in plants are the reasons for their application in medicine, phytotherapy, and aromatherapy. Therefore, reliable, simple, cost-effective, eco-friendly, and rapid methods for the evaluation of antioxidant properties of medicinal plants and products on their basis are required. Electrochemical methods based on electron transfer reactions are promising tools to solve this problem. Total antioxidant parameters and individual antioxidant quantification can be achieved using suitable electrochemical techniques. The analytical capabilities of constant-current coulometry, potentiometry, various types of voltammetry, and chrono methods in the evaluation of total antioxidant parameters of medicinal plants and plant-derived products are presented. The advantages and limitations of methods in comparison to each other and traditional spectroscopic methods are discussed. The possibility to use electrochemical detection of the antioxidants via reactions with oxidants or radicals (N- and O-centered) in solution, with stable radicals immobilized on the electrode surface, via oxidation of antioxidants on a suitable electrode, allows the study of various mechanisms of antioxidant actions occurring in living systems. Attention is also paid to the individual or simultaneous electrochemical determination of antioxidants in medicinal plants using chemically modified electrodes.

Antioxidant Activity of Coffee Components Influenced by Roast Degree and Preparation Method

Coffee is of interest to consumers and researchers, mainly due to its stimulating properties and positive effects on the human body. Properties of coffee infusions depend on many factors and the most important ones include the roasting process and the brew preparation method. In this paper, we analyzed infusions prepared with the use of pressure methods (professional: espresso and consumer: moka pot brew), obtained from beans roasted to the medium and dark degree, with the aim of determining the share of individual groups of ingredients in the antioxidative properties of coffee. Tested infusions showed various characteristics that were partly related to different parameters of their preparation. In general, a greater amount of phenolic compounds was extracted in moka brews. Espresso, on the other hand, exhibited greater antioxidant activity per portion of the brew and a greater ability to quench free radicals. The degree of roasting had an uneven effect on the antioxidant activity of the brews, depending on the method and its mechanism of antioxidant action. The share of activity of the particular groups of antioxidants in overall activity varied between all methods; the most pronounced changes were observed in the espresso brews. The results indicate, however, that the activity of phenols and melanoidins is based on a mixed mechanism of antioxidant action, but in the case of the latter, the mechanism of hydrogen atom transfer may have an advantage.

Review of the antioxidant potential of flavonoids as a subgroup of polyphenols and partial substitute for synthetic antioxidants.

This review describes the antioxidant activity of flavonoids as a subgroup of polyphenols and a partial or entire substitute for synthetic antioxidants. All relevant databases were searched using the terms "Phytochemical", "Polyphenol", and "Flavonoid". The oxidative reaction caused by free radicals is a reason for food spoilage, which causes unpleasant odor, loss of taste, and damaged tissues. The common antioxidants employed in foods include butylated hydroxyanisole, butylated hydroxytoluene, propyl gallate, and tert-butyl hydroquinone. Despite their high efficiency and potency, synthetic antioxidants have adverse effects on the human body, such as causing mutation and carcinogenicity. A whole and a group of them known as polyphenols possess high antioxidant activity. These compounds are potential antioxidants due to their capabilities such as scavenging free radicals, donating hydrogen atoms, and chelating metal cations. The antioxidant mechanism of action of flavonoids is transferring hydrogen atom to 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 hydroxyl groups in their structure is the highest among different flavonoids. In addition to health promotion and some disease prevention effects, various in vitro investigations have indicated that flavonoids possess high antioxidant activity that is comparable with synthetic antioxidants. However, to be commercially available, these compounds should be extracted from a low-price source with a high-performance method.

Does Fipronil Affect on Aquatic Organisms? Physiological, Biochemical, and Histopathological Alterations of Non-Target Freshwater Mussel Species

Fipronil is widely used against insects in agriculture and ectoparasites in domestic areas and veterinary medicine. However, fipronil may influence non-target species as a result of the contamination of aquatic ecosystems. The present study aimed to investigate the acute and sublethal effects of fipronil in freshwater mussels (Unio delicatus), a non-target species, with physiological, antioxidant action mechanisms and histopathological observations. The 96-h LC50 value of fipronil was found to be 2.64 (1.45–4.56) mg/L. Sublethal concentrations were applied at 1/10 and 1/5 of 96-h LC50 as 0.264 mg/L and 0.528 mg/L for 48-h and 7-d. Haemolymph samples, digestive gland and gill tissues of mussels were taken after exposure times. While the Total Haemocyte Counts decreased in 48-h of exposure, it was only high at 0.264 mg/L fipronil-exposed for 7-d (p &lt; 0.05). While glutathione values in digestive glands and gills were higher in the fipronil applied groups (p &lt; 0.05), the AOPP values were only higher in the digestive glands at 7-d of exposure (p &lt; 0.05). Moreover, fipronil caused histopathological alterations on gills and digestive glands. These things considered, the principal component analysis revealed that the most pronounced changes in the antioxidant action mechanisms were caused by the fipronil exposure. These results show that sublethal concentrations of fipronil are toxic to freshwater mussels.

In Vitro Antioxidant Mechanism of Action of Hibiscus Sabdariffa in the Induction of Apoptosis against Breast Cancer

ABSTRACT The antioxidant mechanism of action in the process of cytotoxicity, and pro-apoptotic activity of Hibiscus sabdariffa water extract (HSWE) was assessed against non-cancerous (MCF12A) and breast cancer (MCF7) cells grown in DMEM-F12 and DMEM, respectively. The treated cells revealed a polyphenolic and anthocyanin content of 17.7 ± 0.4 mg g−1 and 24.8 ± 0.5 mg g,−1 respectively. The oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assay values were 1506 ± 30.1 µmoleTE g−1 and 428.9 ± 3.8 µmoleAAE g−1 at 1.0 mg mL−1, respectively, indicating a high antioxidant capacity. The HSWE induced greater apoptosis than doxorubicin (62.5 ± 2.6%), as more cytotoxic effect was noted against MCF7 with 70.4 ± 2.4% than MCF12A (15.3 ± 1.4%) cells at 0.4 mg mL−1. The HSWE depolarized mitochondrial MCF7 by 42.5 ± 0.5% compared to 4.6 ± 0.3% against MCF12A at 0.3 mg mL−1. It altered the intracellular redox status of MCF7 cells by depleting antioxidant enzymes with high levels of lipid peroxidation and reactive oxygen species [ROS] in MCF7 than in MCF12A. HSWE selectively induced apoptosis on MCF7 cells via ROS generation, lipid peroxidation, and mitochondrial dysfunction pathway.

Pharmacological characteristics of intranasal dosage forms containing Ginkgo biloba extracts

Background: This article reviews the pharmacological characteristics of developed dosage forms for intranasal administration. The influence of the type of dosage form on the efficacy of the drug is significant. Gel-like structures are interesting objects for research. Interest in understanding the nature and properties of such structures is due to the variety of effects observed when gels are used. The active ingredient in the studied forms is ginkgo biloba extract obtained by ultrasonic extraction followed by thickening. The object of comparison is standardized dried ginkgo biloba extract (EGB 76). The study of cerebrotropic activity of the developed gels was conducted on the model of bilateral occlusion of the common carotid arteries. The studied objects and the reference preparation were administered therapeutically after modeling cerebral ischemia once a day for 3 weeks. Aim of the study: To evaluate specific pharmacological activity of the developed dosage forms of ginkgo biloba. Materials and Methods: Studies were performed in an appropriate design by simulating cerebral ischaemia in rabbits using simultaneous bilateral occlusion of the common carotid arteries. Changes in cerebral blood flow velocity were performed by Doppler using an appropriate transducer and software package. The data obtained were statistically processed using an application software package. Results: Conducted investigations revealed that under conditions of experimental cerebral ischemia simulated by simultaneous occlusion of the common carotid arteries in large laboratory animals (rabbits), the use of the developed dosage forms promoted the reduction of the severity of neurological deficit, the restoration of cerebral hemodynamics and pro/antioxidant balance in the hippocampus. Conclusions: Developed nasal gels based on chitosan and sodium alginate are promising agents for chronic cerebrovascular accident with antioxidant mechanism of action and therapeutic potential similar to oral administration of standardized ginkgo biloba extract - EGB 761

Kinetics and mechanism of antioxidant action of polysubstituted tetrahydroquinolines in liquid‐phase oxidation reactions of organic compounds by oxygen

AbstractThe antioxidant properties of a series of biologically active polysubstituted tetrahydroquinolines containing chromanyl fragments have been experimentally studied in the liquid phase. Probed was the ability of the substrates to kinetically retard the initiator‐induced radical chain oxidation by O2 of the model compounds 1,4‐dioxane or isopropyl alcohol. The oxidation reactions were monitored at 348 K using a manometric technique, measuring under various initial conditions the time‐dependent concentration of oxygen in the gas phase above a reaction mixture containing the radical‐chain initiator azobisisobutylnitrile and the substrates under study. When tetrahydroquinolines were present, the kinetic curves of oxygen absorption exhibited characteristic induction periods (τ) wherein the reaction rate is immeasurably small. The dependence of τ on the initial concentration of the introduced antioxidants has been determined and the results interpreted within the framework of a classical scheme describing the radical‐chain oxidation of organic compounds in the presence of an inhibitor. Values of the stoichiometric coefficient of inhibition, f, which is related to the number of chain propagating radicals destroyed by each antioxidant molecule, is &gt;&gt;2 for all the studied antioxidants. Consistent with the existing literature, it is inferred that the original antioxidant molecule is regenerated from its radical inhibition product during reaction. Previous studies suggest that oxyperoxy radicals play an important role in the inhibitor regeneration process due to their ability to act either as an oxidizer (in chain propagation) or as a reducing agent (in regeneration of the inhibitor from its corresponding radical). In the presently studied systems containing 1,4‐dioxane, it is argued that the source of oxyperoxy radicals is 2‐hydroxy‐1,4‐dioxane. A reaction mechanism that includes the stages of inhibitor regeneration and that is quantitatively consistent with the present results has been developed. It is suggested that the high antioxidant capacity of the tetrahydroquinoline derivatives is due to their large chain breaking rate constants in conjunction with regeneration of the inhibitor during chain termination processes. The relationship of the studied chemical structures and their antioxidant capacity is discussed.

Attenuation of Oxidative Stress and Cognitive Impairment in Cadmium Chloride-Exposed Wistar Rats Pre-treated with Ethanolic Turmeric Root Extract

Background: Turmeric (Curcuma longa), belonging to the Zingiberaceae family, is a widely used spice in cuisines of African, Asian and other countries globally. Despite the enormous pharmacological benefits of turmeric, there is very little experimental evidence to demonstrate its protective activity against cadmium-induced neurotoxicity. Accordingly, this study is aimed at investigating such activity in Wistar rats and its possible mechanisms of action. Methods: Y-maze and Novel object recognition tests were utilized to evaluate memory impairments while antioxidants activity and lipid peroxidation were evaluated to outline the antioxidant mechanism of action following pre-treatment of rats with ethanolic turmeric root extract (200 mg/kg body weight) 1 hour before cadmium administration for 21 consecutive days. In addition, the histology of the cerebrum and hippocampus was investigated to determine possible anatomical alterations across experimental groups. Results: The ethanolic extract of turmeric root at the dose of 200 mg/kg significantly improved the memory of rats and protected against the impairments induced by cadmium. In addition, the extract significantly increased cerebral and hippocampal antioxidant enzyme activities (SOD, GPx and CAT), decreased lipid peroxidation (MDA) and protected against the degenerative changes observed in the cerebrum and hippocampus of rats treated with cadmium alone. Conclusion: Taken together, these findings suggest that the ethanolic extract of turmeric root protected against the cognitive impairments induced by cadmium possibly through the attenuation of the oxidative damaging activity of cadmium.

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.

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.