Mechanisms Of Antioxidant Action Research Articles

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.

Plant-Based Phenolic Molecules as Natural Preservatives in Comminuted Meats: A Review.

Comminuted meat products are highly susceptible to safety and quality degradation partly because of their large interfacial area in the emulsion. The food industry extensively uses synthetic chemical preservatives to delay that degradation which is caused by microbial growth, enzyme activities and oxidation reactions. However, due to the potential health damage (e.g., cardiovascular diseases, neurodegenerative diseases, cancers among others) synthetic preservatives in meat may cause, consumers are becoming skeptical to buy meat products containing such additives. In the meat industry, the interest of finding natural food preservatives is intensifying. Polyphenolic-rich plants used as natural food preservatives offer the best alternative for a partial or a complete replacement of their synthetic counterparts. They can be extracted from natural sources such as olives, fruits, grapes, vegetables, spices, herbs, and algae, and among others. The common feature of these phenolic compounds is that they have one or more aromatic rings with one or more -OH group which are essential for their antimicrobial and antioxidant properties. This review article is intended to provide an overview of the plant-based phenolic molecules used as natural food preservative, their antimicrobial and antioxidant mechanism of action, and their potential application in comminuted meat.

Antitumor and Antioxidant Activities of the New Synthesized Azomethine Derivatives: Experimental and Theoretical Investigations

In this study, the antioxidant property of eight new azomethine derivatives underwent theoretical and experimental investigations. Azomethines have antioxidant activity. This is the first time the molecular structures and antioxidant property of these derivatives have been studied. The molecular structures were optimized using Density functional theory (DFT). The Bond Dissociation Enthalpy (BDE), Mulliken Charges, NBO analysis, Ionization Potential (IP), Electron Affinities (EA), HOMO and LUMO energies, Hardness (&amp;#951;), Softness (S), Electronegativity (μ), Electrophilic Index (&amp;#969;), Electron Donating Power (&amp;#969;&lt;sup&gt;-&lt;/sup&gt;), Electron Accepting Power (&amp;#969;&lt;sup&gt;+&lt;/sup&gt;), and Energy Gap (E&lt;sub&gt;g&lt;/sub&gt;) were calculated in order to deduce scavenging action of the eight new synthesized azomethines (DIA-3,4,5,6,7,8,9,10). Spin density calculations and NBO analysis were also carried out to understand the antioxidant activity mechanism. These molecules have high antioxidant potential due to the planarity and formation of intramolecular hydrogen bonds. Experimental investigations establish high antioxidant and antitumor activities of the synthesized azomethine derivatives.

Artificial Intelligence (AI) to the Rescue: Deploying Machine Learning to Bridge the Biorelevance Gap in Antioxidant Assays.

Oxidative stress induced by excessive levels of reactive oxygen species (ROS) underlies several diseases. Therapeutic strategies to combat oxidative damage are, therefore, a subject of intense scientific investigation to prevent and treat such diseases, with the use of phytochemical antioxidants, especially polyphenols, being a major part. Polyphenols, however, exhibit structural diversity that determines different mechanisms of antioxidant action, such as hydrogen atom transfer (HAT) and single-electron transfer (SET). They also suffer from inadequate in vivo bioavailability, with their antioxidant bioactivity governed by permeability, gut-wall and first-pass metabolism, and HAT-based ROS trapping. Unfortunately, no current antioxidant assay captures these multiple dimensions to be sufficiently “biorelevant,” because the assays tend to be unidimensional, whereas biorelevance requires integration of several inputs. Finding a method to reliably evaluate the antioxidant capacity of these phytochemicals, therefore, remains an unmet need. To address this deficiency, we propose using artificial intelligence (AI)-based machine learning (ML) to relate a polyphenol’s antioxidant action as the output variable to molecular descriptors (factors governing in vivo antioxidant activity) as input variables, in the context of a biomarker selectively produced by lipid peroxidation (a consequence of oxidative stress), for example F2-isoprostanes. Support vector machines, artificial neural networks, and Bayesian probabilistic learning are some key algorithms that could be deployed. Such a model will represent a robust predictive tool in assessing biorelevant antioxidant capacity of polyphenols, and thus facilitate the identification or design of antioxidant molecules. The approach will also help to fulfill the principles of the 3Rs (replacement, reduction, and refinement) in using animals in biomedical research.

Dairy antioxidant system

A review of dairy antioxidants was done based on local and international sources. Oxidative processes of fat are the main cause of chemical spoilage of milk and dairy products. Lipid oxidation is associated mainly with the amount of unsaturated fatty acids in the shells of fat globules and plasma phospholipids, as well as with the amount of free fat. The products of oxidative reactions at different stages of lipid oxidation with atmospheric oxygen are fatty acid hydroperoxides, peroxides, aldehydes, ketones, hydroxy acidswhich not only worsen the organoleptic characteristics of milk, but some of them are toxic substances. The antioxidant ability of milk is due to vitamins A, C, E, carotenoids, enzymes, lactoferin, sulfur-containing amino acids. One of the most powerful natural antioxidants is ascorbic acid, which is able to absorb superoxide anion radicals, alkoxyl radicals, superoxide, iron oxide, nitric oxide. Group E vitaminsare described, being the primary fat-soluble antioxidants. Among this group of substances, the most biologically active form is ?-tocopherol. The contribution of carotenoids to antioxidant protection has been determined. Beta carotene is considered as a preventive antioxidant, as it can block singlet oxygen which ishighly toxic. The mechanisms of antioxidant action of various enzymes are disclosed. Xanthioxidase has been shown to oxidize various aldigides and purine bases to the corresponding acids. Lactoperoxidase catalyzes the oxidation of thiocyanate with hydrogen peroxide to form thiociagen. Catalase oxidizes hydrogen peroxide to form water and molecular oxygen. Glutathione peroxidase is capable of rapidly removing hydrogen peroxide and other peroxides. The mechanism of the antioxidant action of lactoferrin is described which is based on iron the chelation by it. The functions of sulfur-containing amino acids due to the binding of free radicals are disclosed. Determining the total antioxidant activity can be a biomarker of its biological value, which will allow to choose the most perspective areas of milk processing..

Study of Antioxidant Properties of Agents from the Perspective of Their Action Mechanisms.

The creation and analysis of a large variety of existing methods for the evaluation of integrated antioxidant properties are quite relevant in connection with a range of biological mechanisms of the antioxidants (AO) action. In this work, the existing methods are correlated with mechanisms of antioxidant action. It is shown that the results obtained by various methods are mainly incomparable. This can be connected with the implementation of various mechanisms of antioxidant action in methods. The analysis of the literature data presented in this review indicates the difficulty of creating a universal method and the feasibility of using integrated approaches based on the use of several methods that implement and combine various mechanisms of the chemical conversion of antioxidants. This review describes methods for studying the chelating ability of antioxidants, except for methods based on electron and hydrogen atom transfer reactions, which are currently not widely covered in modern literature. With the description of each mechanism, special attention is paid to electrochemical methods, as the interaction of active oxygen metabolites of radical and non-radical nature with antioxidants has an electron/proton/donor-acceptor nature, which corresponds to the nature of electrochemical methods and suggests that they can be used to study the interaction.

Eggshell Biliverdin as an Antioxidant Maternal Effect: Biliverdin as an Antioxidant Resource in Oviparous Animals.

In this essay, the hypothesis that biliverdin pigment plays an antioxidant role in the avian eggshell is proposed. Due to its ability to scavenge free radical species and to reduce mutation, biliverdin potentially counteracts the oxidative action of pathogens that penetrate the eggshell and/or protects the shell membrane from oxidation, thus promoting the proven antioxidant and antimicrobial capacities of the shell membrane itself. Additionally, biliverdin may be able to inhibit viral replication in the eggshell due to its ascribed antiviral properties. Moreover, previous results in other taxa leave open the question of whether biliverdin can be absorbed by the embryo from the eggshell and play a role in embryogenesis. These mechanisms of antioxidant action of eggshell biliverdin remain totally unexplored in birds and in other oviparous animals. The main assumptions and predictions of the antioxidant hypothesis are developed, and directions for future research are proposed.

A Lipid-Based Oral Supplement Protects Skin Cells in Culture from Ultraviolet Light and Activates Antioxidant and Anti-Inflammatory Mechanisms

Overexposure to ultraviolet (UV) light is associated with multiple health risks, from sunburn and prematurely aging skin to the development of skin cancers. The ingestion of photoprotective natural compounds through diet or supplementation is one method to increase the skin’s UV-resistance. This study’s primary objective was to determine the cellular photoprotective properties of an ingestible skincare supplement (trade name “Anti-Aging Formula” [AAF]) and compare them to its constituent active ingredients: fish oil-derived omega-3s eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), borage-derived omega-6 gamma-linolenic acid (GLA), paprika- and marigold-derived carotenoids, zeaxanthin and lutein, respectively, and vitamin D3. AAF, but not the separate individual ingredients, significantly increased the viability of primary human dermal fibroblasts after UVA exposure compared to the vehicle control. AAF and EPA/DHA-containing fish oil demonstrated similar UVB photoprotective properties whereas GLA, the carotenoids, and vitamin D3 had no significant effect. The second objective was to explore possible mechanisms of action of AAF’s photoprotective effects. AAF-treatment increased cellular antioxidant activity and the expression of genes in the glutathione and peroxiredoxin (PRDX)/thioredoxin (TXN) antioxidant pathways, suggesting an antioxidant mechanism of action. It also diminished cellular arachidonic acid (AA) levels and decreased the expression of the downstream pro-inflammatory prostaglandin-endoperoxide synthase 2 (PTGS2) gene, suggesting an anti-inflammatory mechanism of action. In conclusion, AAF is UVA/B photoprotective when applied directly to primary human dermal fibroblasts. In addition, its photoprotective effects are mainly due to its EPA/DHA components and may relate to its cellular antioxidant effects and inhibition of the AA/PTGS2 inflammatory pathway.

ANTIOXIDATIVE AND INHIBITION POTENCY OF CYNODONTIN

The antioxidant activity of cynodontin was studied in the absence and the presence of free radical species. This in silico study was performed in water and benzene, with the aim to simulate polar and non-polar environment. To determine the most probable mechanism of antioxidant action, density functional theory (DFT) was employed. The change in reaction enthalpy of cynodontin with three different free radicals (hydroxyl, hydroperoxyl, and methyl peroxyl radical) were examined and presented. SET-PT (Single Electron Transfer – Proton Transfer) mechanism is not an operative mechanism of antioxidant action. The obtained results imply that the possible mechanism of antioxidant action in water is SPLET (Sequential Proton Loss Electron Transfer), while in benzene HAT (Hydrogen atom transfer) and SPLET are competitive mechanisms. The molecular docking study was performed in order to estimate the inhibition potency of the investigated compound toward human leukocyte elastase (HLE). The obtained results indicate that numerous interactions determine the inhibition activity towards the investigated protein.

An integrated approach to the investigation of antioxidant properties by potentiometry

An analytical methodology is proposed for a comprehensive study of antioxidant properties of various objects based on the implementation of various mechanisms of antioxidant action. In order to interpret results regarding the action of antioxidants in living organisms it is proposed to adhere to certain requirements for research methods of antioxidant properties, for oxidizing agents of a radical and non-radical nature. The developed integrated approach consists in using the potentiometry method and is based on the antioxidant capacity determination which is founded on the interaction of antioxidants with the К3[Fe(CN)6] by the ET-mechanism and the conjugation mechanism and the antiradical capacity determination based on the interaction of antioxidants with peroxyl radicals by the HAT-mechanism. Individual antioxidants of natural origin, plant materials extracts as well as synthesized 6-nitro-1,2,4-triazoloazin containing polyphenols fragments, which are complex conjugated structures, have been investigated. It has been shown that in the antioxidants study it is advisable to use the integrated approach that will allow to evaluate antioxidant properties from the point of view of various antioxidants action mechanisms.

Combined infrared spectroscopic and computational study on simpler capsaicin derivatives and their anion intermediates in the scavenging of free radicals

Two capsaicin analogues – N-(4-hydroxy-3-methoxybenzyl)acetamide and N-(4-hydroxy-3-methoxybenzyl)benzamide, were studied by DFT methods in order to estimate their ability to act as antioxidants. A comparative study on the stability of benzylic, phenoxyl and amide radicals has outlined the most reactive site for hydrogen atom abstraction and proton transfer. The enthalpies related to the formation of those species were modeled in gas phase, benzene, DMSO and water in order to determine the most probable mechanism of antioxidant action in polar and nonpolar medium. The formation of phenoxyl anion, energetically favoured in polar medium, was investigated by infrared spectroscopy methods based on the conversion of the benzamide derivative.

Comparative study of the antioxidant effects of lavender and flax oils in recurrent aphthous ulceration treatment

Background: Recurrent aphthous ulceration (RAU) is an inflammatory condition of unknown etiology characterized by painful recurrent (single or multiple) ulcerations of the oral mucosa. It is one of the most common and poorly understood mucosal disorders. It occurs more frequently in times of stress. Local and systemic conditions, genetic, immunologic, microbial factors, and oxidative stress may play a role in the pathogenesis of RAU. The objective of this study was to evaluate the free radical metabolism and antioxidant activity of RAU patients treated by lavender or flax oil paint.&#x0D; Materials and Methods: Sixty-six RAU patients were enrolled in this prospective randomized double-blind placebo-controlled study. Analysis of the plasma levels of malondialdehyde (MDA), glutathione (GSH), Nitric oxide (NO), myeloperoxidase (MPO), Vit. E, Vit. C, and Trolox equivalent antioxidant capacity (TEAC) were determined. The ulcer size, healing time, and healing process were correlated to the plasma levels of the studied parameters for the assessment of the antioxidant mechanism of action of lavender and flax oil paint in the treatment of RAU.&#x0D; Results: Statistical analysis showed that lavender antioxidant action was higher than flax oil paint compared to placebo. The decreased oxidative stress and the damage caused by free radicals was significant in the lavender group than both flax group and placebo (P&lt;0.001).&#x0D; Conclusion: This study proves the significant antioxidant mechanism of both lavender and flax in the treatment of RAU patients.&#x0D; Keywords: Recurrent aphthous ulceration (RAU), oxidative stress, antioxidants, lavender, flax

Evaluation of Antioxidant Activity of Spice-Derived Phytochemicals Using Zebrafish.

Various dietary phytochemicals seem to display antioxidant activity through the NF-E2-related factor 2 (Nrf2) pathway. However, few studies have demonstrated its antioxidant effect and Nrf2 dependency at the animal level. We constructed a zebrafish-based assay system to analyze the in vivo antioxidant activity of phytochemicals and examined the activity of 10 phytochemicals derived from spices, using this system as a pilot study. Hydrogen peroxide and arsenite were used as oxidative stressors, and Nrf2 dependency was genetically analyzed using an Nrf2-mutant zebrafish line. The activities of curcumin, diallyl trisulfide and quercetin were involved in the reduction of hydrogen peroxide toxicity, while those of cinnamaldehyde, isoeugenol and 6-(methylsulfinyl)hexyl isothiocyanate were involved in the reduction of arsenite toxicity. The antioxidant activities of these phytochemicals were all Nrf2 dependent, with the exception of cinnamaldehyde, which showed strong antioxidant effects even in Nrf2-mutant zebrafish. In summary, we succeeded in constructing an assay system to evaluate the in vivo antioxidant activity of various phytochemicals using zebrafish larvae. Using this system, we found that each spice-derived phytochemical has its own specific property and mechanism of antioxidant action.

Клінічна ефективність стоматологічного NBF Gingival Gel при лікуванні пацієнтів із запальними захворюваннями пародонту

Purpose. To examine the effectiveness of using local nano-gel NBF Gingival Gel at the stage of primary periodontal therapy of patients with chronic catarrhal gingivitis and generalized periodontitis based on the use of clinical and biochemical research methods. Methods. Appreciate the effectiveness of local nano-gel NBF Gingival Gel with the objective of periodontal indices, monitoring of patients and biochemical studies content in the oral fluid (OF) of indices of free radical oxidation (MDA) and antioxidant defense (glutathione reductase). Results. Usage of nano-gel NBF Gingival Gel at the stages of primary periodontal therapy for 80 patients with chronic catarrhal gingivitis (CCG) and generalized periodontitis (GP) I, I–II degree demonstrated good clinical anti-inflammatory effect, which based on its pronounced antioxidant and antimicrobial mechanisms of action. NBF Gingival Gel is not irritating of periodontal tissues and the mucous membrane of the oral cavity, has good organoleptic qualities. Conclusions: In addition to basic treatment in primary periodontal therapy of patients with inflammatory periodontal disease should be to use local drugs with directed pathogenetic mechanism of action, which include nano-gel NBF Gingival Gel with antioxidant mechanism of action.

Многофункциональные алкилфенолятные присадки к моторным маслам

Sulphur-containing multifunctional additives 144 and 144d were synthesized and investigated, which are the calcium salt of the condensation product of alkylphenol with formaldehyde and sodium sulphide. It was found that synthesized additives for their antioxidative and anticorrosive properties surpass the marketable analogues ЦИАТИМ-339 and ИXП-101. The mechanism of antioxidant action of additives AKİ-144 and AKİ-144d in comparison with the industrial antioxidant Agidol-1 was also studied under simulative conditions. Comparative studies have shown that for antioxidant properties the synthesized additives are higher than Agidol-1.

Hormetic and Mitochondria-Related Mechanisms of Antioxidant Action of Phytochemicals

Antioxidant action to afford a health benefit or increased well-being may not be directly exerted by quick reduction-oxidation (REDOX) reactions between the antioxidant and the pro-oxidant molecules in a living being. Furthermore, not all flavonoids or polyphenols derived from plants are beneficial. This paper aims at discussing the variety of mechanisms underlying the so-called “antioxidant” action. Apart from antioxidant direct mechanisms, indirect ones consisting of fueling and boosting innate detox routes should be considered. One of them, hormesis, involves upregulating enzymes that are needed in innate detox pathways and/or regulating the transcription of the so-called vitagenes. Moreover, there is evidence that some plant-derived compounds may have a direct role in events taking place in mitochondria, which is an organelle prone to oxidative stress if electron transport is faulty. Insights into the potential of molecules able to enter into the electron transport chain would require the determination of their reduction potential. Additionally, it is advisable to know both the oxidized and the reduced structures for each antioxidant candidate. These mechanisms and their related technical developments should help nutraceutical industry to select candidates that are efficacious in physiological conditions to prevent diseases or increase human health.

Study of Influence of Free Radical Species on Antioxidant Activity of Selected 1,2,4‐Triazole‐3‐thiones

AbstractThe free radical scavenging potency of four 1,2,4‐triazole‐3‐thione compounds towards ten chosen radicals was investigated. The thermodynamic parameters, Gibbs free energies of reactions and reaction enthalpies, were used to determine the most probable mechanism of action. The results indicated that the favourable mechanism of antiradical action was dependent both on the polarity of solvents and a nature of free radical species. The results suggested that Sequential Proton Loss Electron Transfer (SPLET) is the most probable for reaction in benzene, while Hydrogen Atom Transfer (HAT) was favorized for reaction occurring in methanol. The constant competition between these mechanisms of antioxidative action was present. The molecular docking study, obtained for parent molecules of chosen 1,2,4‐triazole‐3‐thiones compounds and their corresponding anionic species, showed their inhibitory nature against histidine kinase inhibitor Sda. Except in the case of compound 4 a, all the anionic species (4 d‐4 h) showed the lower inhibition constants, indicating better inhibition potency of Sda, than corresponding parent molecules.

Phenolic betalain as antioxidants: meta means more

Abstract Betalains are phytochemicals of nutraceutical importance that emerged as potent antioxidants, preventing radical chain propagation and the deleterious health effects of oxidative stress. However, despite the wide application of betalains as color additives in products for human consumption, little is known about the relationship between their structure and antioxidant potential. Here we investigate the mechanism of antioxidant action of three regioisomeric phenolic betalains and show that the meta isomer has higher antiradical capacity than most natural betalains, anthocyanins and flavonoids. Structural and pH effects on redox and antiradical properties were investigated and the results are rationalized in light of quantum chemical calculations. Our results demonstrate that hydrogen atom transfer/proton-coupled electron transfer or sequential proton loss electron transfer mechanisms are plausible to explain the radical chain breaking properties of phenolic betalains in water. Furthermore, mesomeric effects are responsible for the stabilization of the resulting radical phenolic betalains. These findings are useful for the design of biocompatible antioxidants and for the development of novel additives for functional foods and cosmetics with high antioxidant potential.

Antioxidant Activity of Collagen Extracts Obtained from the Skin and Gills of Oreochromis sp.

Efforts aimed at reduction of fishing waste generated during the evisceration and filleting are scarce. The fishing waste is used in the production of low value-added products, such as flours or silages. It is important to visualize an alternative and profitable use of this waste, as it constitutes a serious environmental problem. This research determined the antioxidant properties of collagenous extracts of skin and galls of Oreochromis sp. The raw materials were characterized by proximal chemical analysis. Three treatments were applied to extract the collagen: salt-soluble collagen, acid-soluble collagen (ASC), and pepsin-hydrolyzed collagen (PHC). The collagenous fractions were hydrolyzed (0.1% pepsin). The recovered collagen yield and antioxidant activity were determined to hydrolyzed collagen (HC) and nonhydrolyzed collagen (NHC). The ASC skin showed the highest extraction yield (3.02%). For galls, only the PHC extraction was feasible (0.16%). Antioxidant analysis of NHC did not reveal radical scavenging activities. HC displayed a 2,2-diphenyl-1-picrylhydrazyl %RSA of 22.58 (ASC skin) and 10.34% (PHC galls), and a 2,2'-azino-bis[3-ethylbenzothiazoline-6-sulfonic acid] %RSA of 30.40% (PHC skin) and 29.43% (PHC galls), respectively. The ASC skin and PHC gall extracts exhibited 94.40% and 81.54% in ferric-reducing antioxidant power, and 43.63 and 38.08 μg ascorbic acid equivalents per milli liter for total antioxidant capacity, respectively. The collagen extracts showed %RSA and chelation of pro-oxidant metal ions. Different mechanism of antioxidant action was identified for the extracts: radical scavengers for HC and metal ion chelators for NHC. In conclusion, red tilapia skin collagen is recommended as an active ingredient of nutraceuticals, pharmaceuticals, or functional foods, for the identified bioactive properties.

A novel, highly-water-soluble apigenin derivative provides neuroprotection following ischemia in male rats by regulating the ERK/Nrf2/HO-1 pathway

6"-O-succinylapigenin [apigenin-7-O-(6′-O-succinyl)-glucoside], a novel compound, is identified in chamomile. Although it is highly produced by Bacillus amyloliquefaciens FJ18, its bioactivity remains unknown. The neuroprotective effects and antioxidative mechanism of 6''-O-succcinylapigenin in the middle cerebral artery occlusion model in male rats was investigated in this study. The structure of this compound was determined by spectroscopic data analysis. After 2 h of occlusion and 24 h of reperfusion, magnetic resonance imaging and assessed neurological scores following middle cerebral artery occlusion (MCAO) in male rats to determine the infarction size and neurological deficits, respectively. In addition, we tested protein levels of the nuclear factor E2-related factor 2 (Nrf2), Kelch-like ECH-associated protein1 (Keap1), heme oxygenase-1 (HO-1), and extracellular-signal-regulated kinase (ERK), to investigate the mechanism of antioxidative action of 6''-O-succcinylapigenin. Finally, we employed immunofluorescence to determine the location of Nrf2 and Keap1 in HT22 cells cultured in vitro. Our results revealed that administration of 6''-O-succcinylapigenin induced a decrease in both infarct volume and neurological scores following MCAO, and significantly increased the activity of HO-1 and nuclear Nrf2 in vivo. Similarly, immunofluorescence assays indicated that Nrf2 is highly expressed in the nucleus following treatment with 6''-O-succcinylapigenin in vitro. Our study suggests that 6''-O-succcinylapigenin exerts an anti-ischemic effect by activating the ERK/Nrf2/HO-1 pathway.