Direct Antioxidant Effects Research Articles

Increasing germination and antioxidant activity of aged wheat and triticale grains by priming with gamma-aminobutyric acid

During storage, elevated temperature and humidity cause accelerated aging and deterioration of seeds of various plant species, including important cultivated cereals, such as wheat and triticale. Germination of old seeds can be facilitated by seed priming with physiologically active substances that correct the pro/antioxidant balance and reduce the development of oxidative stress. Gamma-aminobutyric acid (GABA) is a regulatory compound with direct and indirect antioxidant effects. However, its effect on the germination of grains of cereals with low germination has not been extensively studied. The objective of this study was to examine the impact of GABA priming on the germination of aged grains of winter bread wheat (Triticum aestivum ‘Scorpion’) and winter triticale (×Triticosecale ‘Raritet’). the extent of oxidative stress and the state of the antioxidant system in seedlings. The results indicated that a three-hour treatment of grains with GABA at the optimal concentration (1 mM) resulted in a significant (18–21%) increase in germination energy and seed germination rate, as well as an increase in the biomass of shoots and roots of seedlings of both species. Concomitantly, the influence of GABA resulted in a reduction in oxidative stress markers, including the generation of superoxide anion radicals, hydrogen peroxide content, and the product of lipid peroxidation malondialdehyde. In wheat seedlings, the total content of phenolic compounds increased, while in triticale seedlings, the content of anthocyanins increased almost twofold. In seedlings derived from GABA-primed grains, catalase activity was also significantly elevated in the absence of notable alterations in superoxide dismutase and peroxidase activity. It was postulated that GABA priming is a promising approach for enhancing the germination of cereal seeds with diminished sowing quality.

Dual Phytochemical/Activity-Guided Optimal Preparation and Bioactive Material Basis of Orthosiphon Stamineus Benth. (Shen Tea) against Nonalcoholic Fatty Liver Disease.

Orthosiphon stamineus Benth. (OSB) is a popular plant used for making "Shen tea" or "Java tea". It has been demonstrated with antioxidant, anti-inflammatory, and hepatoprotective activities. However, its potential beneficial effects and bioactive material basis for nonalcoholic fatty liver disease (NAFLD) has not been convincingly studied. In the present work, we conducted dual phytochemical/activity-guided extraction optimization and component fractionation of OSB, and evaluated its beneficial effects on NAFLD. Flavonoids and polyphenols (caffeic acid/protocatechuic acid derivatives) were determined as the dominant phytochemicals in OSB. The extraction process for these phytochemicals was optimized by using response surface methodology. Noticeably, flavonoids showed a stronger correlation with the antioxidant activities of OSB than polyphenols. Likewise, the flavonoid-rich fraction of OSB exerted antioxidant activities stronger than those of other fractions. As expected, in vitro and in vivo studies demonstrated that the flavonoid-rich fraction effectively attenuated weight increase, improved lipid metabolism, alleviated hepatic steatosis, and reversed hepatic inflammation. Importantly, this fraction showed equivalent beneficial effects to the total extract of OSB, suggesting that flavonoids were the main bioactive constituents of OSB. The action mechanism was indicated as direct antioxidant effect through chemical interaction with free radicals and indirect mitochondria-mediated antioxidant defense. Our research offers bioactive substances for further exploitation and expands the potential application of OSB.

Apigenin's Modulation of Doxorubicin Efficacy in Breast Cancer.

Apigenin, a naturally derived flavonoid, is increasingly being acknowledged for its potential therapeutic applications, especially in oncology. This research explores apigenin's capacity to modulate cancer cell viability, emphasizing its roles beyond its minimal antioxidant activity attributed to its basic molecular structure devoid of hydroxyl groups. We investigated apigenin's effects on two breast cancer cell lines, estrogen-dependent MCF-7 and non-estrogen-dependent MDA-MB-231 cells. Our findings reveal that apigenin exerts a dose-dependent cytotoxic and anti-migratory impact on these cells. Interestingly, both apigenin and doxorubicin-a standard chemotherapeutic agent-induced lipid droplet accumulation in a dose-dependent manner in MDA-MB-231 cells. This phenomenon was absent in MCF-7 cells and not evident when doxorubicin and apigenin were used concurrently, suggesting distinct cellular responses to these treatments that imply that their synergistic effects might be mediated through mechanisms unrelated to lipid metabolism. A further chemoinformatics analysis indicated that apigenin and doxorubicin might interact primarily at the level of ATP-binding cassette (ABC) transporter proteins, with potential indirect influences from the AKT and MYC signaling pathways. These results highlight the importance of understanding the nuanced interactions between apigenin and conventional chemotherapeutic drugs, as they could lead to more effective strategies for cancer treatment. This study underscores apigenin's potential as a modulator of cancer cell dynamics through mechanisms independent of its direct antioxidant effects, thereby contributing to the development of flavonoid-based adjunct therapies in cancer management.

Phloretin prolongs lifespan of Caenorhabditis elegans via inhibition of NDUFS1 and NDUFS6 at mitochondrial complex Ⅰ

Phloretin has been widely perceived as an antioxidant. However, the bioavailability of phloretin in vivo is generally far too low to elicit a direct antioxidant effect by scavenging reactive oxygen species (ROS). Here we showed that administration of phloretin of apple polyphenols extended lifespan of Caenorhabditis elegans and promoted fitness. Specially phloretin enhanced the survival rates of nematodes under oxidants in an inverted U-shaped dose-response manner. The lifespan-extending effects of phloretin were mediated by ROS via mitochondrial complex I inhibition. The increase of ROS stimulated p38 MAPK/PMK-1 as well as transcription factors of NRF2/SKN-1 and FOXO/DAF-16. Consistent with the involvement of NRF2/SKN-1 and FOXO/DAF-16 in lifespan-extending effects, activities of superoxide dismutase (SOD) and catalase (CAT) were enhanced by phloretin. The exogenous application of antioxidants butylated hydroxyanisole and N-acetylcysteine abolished the increase of ROS, the enhancement of SOD and CAT activities, and the lifespan extending effects of phloretin. Meanwhile, with the inhibition of mitochondrial complex I, ATP was instantly decreased. Both energy sensors of AMPK/AAK-2 and SIRT1/SIR-2.1 were involved in the lifespan extension by phloretin. Transcriptomic, real-time qPCR and molecular docking analyses demonstrated that the binding of phloretin at complex I located at NDUFS1/NUO-5, NDUFS2/GAS-1, and NDUFS6/NDUF-6. The molecular dynamic simulation and binding free energy calculations showed that phloretin had high binding affinities towards NDUFS1 (−7.21 kcal/mol) and NDUFS6 (−7.02 kcal/mol). Collectively, our findings suggested phloretin had effects of life expectancy enhancement and fitness promotion via redox regulations in vivo. NDUFS1/NUO-5 and NDUFS6/NDUF-6 might be new targets in the lifespan and wellness regulations.

Antioxidant activity of chia flour as a food supplement in a cellular model: Repercussions of processing and in vitro digestion

Food processing and digestion can alter bioactive compound composition of food, affecting their potential biological activity. In this study, we evaluated the direct and protective antioxidant effects of polyphenols extracted from defatted chia flour (DCF) (salviaflaside, rosmarinic and fertaric acid as major compounds), sweet cookies supplemented with DCF (CFC) (same major compounds), and their digested fractions (rosmarinic acid, salviaflaside, fertaric and salvianolic E/B/L acid as major compounds) in HepG2 cells in basal and in oxidative stress conditions. DCF showed protective antioxidant effects by decreasing reactive oxygen species (ROS) and protein oxidation products (POP) while increasing reduced glutathione (GSH). Additionally, CFC revealed similar protective effects and even showed enhanced modulation of the antioxidant system due to the activation of antioxidant enzymes. However, the digested fractions only decreased ROS, indicating continued antioxidant effects. This study underscores the importance of evaluating manufacturing and digestion effects to confirm a food's antioxidant properties.

Demethylcalabaxanthone from Garcinia mangostana Exerts Antioxidant Effects through the Activation of the Nrf2 Pathway as Assessed via Molecular Docking and Biological Evaluation.

Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway activation promotes the expression of antioxidant enzymes in response to rising oxidative stress, resulting in reactive oxygen species (ROS) detoxification and playing a central role in the maintenance of intracellular redox homeostasis and regulation of inflammation. Moreover, the biological effects of Nrf2 pathway activation contribute to reducing apoptosis and enhancing cell survival. The activity of Nrf2 is negatively regulated by Kelch-like ECH-associated protein 1 (Keap1). Prompted by the recent results reporting the impact of xanthone metabolites on oxidative stress, cancer, and inflammation, the antioxidant properties of xanthones isolated from Garcinia mangostana (γ-mangostin, α-mangostin, 8-deoxygartanin, demethylcalabaxanthone, garcinone D) were assessed. In particular, the capability of these natural products to disrupt the interaction between Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2), triggering the activation of the Nrf2-mediated pathway, was evaluated using molecular docking experiments and in vitro tests. The modulation of some key Nrf2-related mediators like glutathione (GSH) and lactate dehydrogenase (LDH) to highlight a possible direct antioxidant effect was investigated. Among the tested compounds, demethylcalabaxanthone showed an indirect antioxidant effect, as corroborated by a Western blot assay, displaying a significant increase in the translocated protein upon its administration.

Biliverdin as a disease-modifying agent: An integrated viewpoint.

Biliverdin is one of the three by-products of heme oxygenase (HO) activity, the others being ferrous iron and carbon monoxide. Under physiological conditions, once formed in the cell, BV is reduced to bilirubin (BR) by the biliverdin reductase (BVR). However, if BVR is inhibited by either genetic variants, as occurs in the Inuit ethnicity, or dioxin intoxication, BV accumulates in cells giving rise to a clinical syndrome known as green jaundice. Preclinical studies have demonstrated that BV not only has a direct antioxidant effect by scavenging free radicals, but also targets many signal transduction pathways, such as BVR, soluble guanylyl cyclase, and the aryl hydrocarbon receptor. Through these direct and indirect mechanisms, BV has shown beneficial roles in ischemia/reperfusion-related diseases, inflammatory diseases, graft-versus-host disease, viral infections and cancer. Unfortunately, no clinical data are available to confirm these potential therapeutic effects and the kinetics of exogenous BV in humans is unknown. These limitations have so far excluded the possibility of transforming BV from a mere by-product of heme degradation into a disease-modifying agent. A closer collaboration between basic and clinical researchers would be advantageous to overcome these issues and promote translational research on BV in free radical-induced diseases.

Cocoa Shell Extract Reduces Blood Pressure in Aged Hypertensive Rats via the Cardiovascular Upregulation of Endothelial Nitric Oxide Synthase and Nuclear Factor (Erythroid-Derived 2)-like 2 Protein Expression.

Cocoa shell is a by-product of cocoa manufacturing. We obtained an aqueous extract (CSE) rich in polyphenols and methylxanthines with antioxidant and vasodilatory properties. We aimed to evaluate the effects of CSE supplementation in aged hypertensive rats on blood pressure and the mechanism implicated. Eighteen-month-old male and female rats exposed to undernutrition during the fetal period who developed hypertension, with a milder form in females, were used (MUN rats). Systolic blood pressure (SBP; tail-cuff plethysmography) and a blood sample were obtained before (basal) and after CSE supplementation (250 mg/kg; 2 weeks, 5 days/week). Plasma SOD, catalase activity, GSH, carbonyls, and lipid peroxidation were assessed (spectrophotometry). In hearts and aortas from supplemented and non-supplemented age-matched rats, we evaluated the protein expression of SOD-2, catalase, HO-1, UCP-2, total and phosphorylated Nrf2 and e-NOS (Western blot), and aorta media thickness (confocal microscopy). MUN males had higher SBP compared with females, which was reduced via CSE supplementation with a significant difference for group, sex, and interaction effect. After supplementation with plasma, GSH, but not catalase or SOD, was elevated in males and females. Compared with non-supplemented rats, CSE-supplemented males and females exhibited increased aorta e-NOS and Nrf2 protein expression and cardiac phosphorylated-Nrf2, without changes in SOD-2, catalase, HO-1, or UCP-2 in cardiovascular tissues or aorta remodeling. In conclusion, CSE supplementation induces antihypertensive actions related to the upregulation of e-NOS and Nrf2 expression and GSH elevation and a possible direct antioxidant effect of CSE bioactive components. Two weeks of supplementation may be insufficient to increase antioxidant enzyme expression.

Omega-3 Polyunsaturated Fatty Acids and Their Anti-Oxidant, Anti-Inflammatory and Neuroprotective Effects in Diabetic Retinopathy: A Narrative Review.

Diabetic retinopathy (DR) is a common microvascular complication of type 2 Diabetes Mellitus (T2DM) that can have vision-threatening consequences, particularly if it advances to the proliferative stage and is left untreated. Owing to the central role of hyperglycemia-induced oxidative stress, multiple anti-oxidants have been investigated for their therapeutic value. However, there is a lack of substantial data to support the use of any of the compounds tested so far. Omega-3 polyunsaturated fatty acids (PUFAs), namely docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), have received much acclaim for their positive impact on cardiovascular health outcomes. The anti-oxidative, anti-inflammatory and neuroprotective properties of PUFAs also make them promising therapeutic and preventive agents for DR. The current evidence is derived mainly from in vitro and animal studies and provides some insight into the underlying mechanisms involved. These fatty acids are capable of direct anti-oxidative and anti-inflammatory effects. They also concomitantly promote intrinsic defense mechanisms and recovery, particularly of photoreceptor neurons. Hence, dietary supplementation with PUFAs, mainly from marine sources, can halt and reverse the retinal damage seen in DR. Furthermore, clinical trials have reported improved vision and quality of life in DR patients after supplementation. However, a major limitation of these trials is the use of nutraceutical formulations in which omega-3 PUFAs are combined with other anti-oxidant compounds, thereby preventing the evaluation of omega-3 as standalone treatment. Although the results of experimental studies to date have been promising, more clinical trials are required to determine the full extent of benefits in patients with DR.

Sulforaphane Attenuates Neutrophil ROS Production, MPO Degranulation and Phagocytosis, but Does Not Affect NET Formation Ex Vivo and In Vitro.

Sulforaphane has several effects on the human body, including anti-inflammation, antioxidation, antimicrobial and anti-obesity effects. In this study, we examined the effect of sulforaphane on several neutrophil functions: reactive oxygen species (ROS) production, degranulation, phagocytosis, and neutrophil extracellular trap (NET) formation. We also examined the direct antioxidant effect of sulforaphane. First, we measured neutrophil ROS production induced by zymosan in whole blood in the presence of 0 to 560 µM sulforaphane. Second, we examined the direct antioxidant activity of sulforaphane using a HOCl removal test. In addition, inflammation-related proteins, including an azurophilic granule component, were measured by collecting supernatants following ROS measurements. Finally, neutrophils were isolated from blood, and phagocytosis and NET formation were measured. Sulforaphane reduced neutrophil ROS production in a concentration-dependent manner. The ability of sulforaphane to remove HOCl is stronger than that of ascorbic acid. Sulforaphane at 280 µM significantly reduced the release of myeloperoxidase from azurophilic granules, as well as that of the inflammatory cytokines TNF-α and IL-6. Sulforaphane also suppressed phagocytosis but did not affect NET formation. These results suggest that sulforaphane attenuates neutrophil ROS production, degranulation, and phagocytosis, but does not affect NET formation. Moreover, sulforaphane directly removes ROS, including HOCl.

Priming Potato Plants with Melatonin Protects Stolon Formation under Delayed Salt Stress by Maintaining the Photochemical Function of Photosystem II, Ionic Homeostasis and Activating the Antioxidant System.

Melatonin is among one of the promising agents able to protect agricultural plants from the adverse action of different stressors, including salinity. We aimed to investigate the effects of melatonin priming (0.1, 1.0 and 10 µM) on salt-stressed potato plants (125 mM NaCl), by studying the growth parameters, photochemical activity of photosystem II, water status, ion content and antioxidant system activity. Melatonin as a pleiotropic signaling molecule was found to decrease the negative effect of salt stress on stolon formation, tissue water content and ion status without a significant effect on the expression of Na+/H+-antiporter genes localized on the vacuolar (NHX1 to NHX3) and plasma membrane (SOS1). Melatonin effectively decreases the accumulation of lipid peroxidation products in potato leaves in the whole range of concentrations studied. A melatonin-induced dose-dependent increase in Fv/Fm together with a decrease in uncontrolled non-photochemical dissipation Y(NO) also indicates decreased oxidative damage. The observed protective ability of melatonin was unlikely due to its influence on antioxidant enzymes, since neither SOD nor peroxidase were activated by melatonin. Melatonin exerted positive effects on the accumulation of water-soluble low-molecular-weight antioxidants, proline and flavonoids, which could aid in decreasing oxidative stress. The most consistent positive effect was observed on the accumulation of carotenoids, which are well-known lipophilic antioxidants playing an important role in the protection of photosynthesis from oxidative damage. Finally, it is possible that melatonin accumulated during pretreatment could exert direct antioxidative effects due to the ROS scavenging activity of melatonin molecules.

The Effect of Phycocyanin Isolated from Arthrospira platensis on the Oxidative Stress in Yeasts

C-phycocyanin, being a component of the photosynthetic apparatus of cyanobacteria, is an effective antioxidant and anti-inflammatory agent and is often used in medical studies. The intracellular effect of C-phycocyanin isolated from cyanobacteria Arthrospira platensis on the levels of the prooxidant-induced oxidative stress and cell death of the aerobic yeast Yarrowia lipolytica is considered. We show that C-phycocyanin accumulated in the yeast cells and had a direct antioxidant effect on the yeast suspension within the concentration range of 10–100 μg/mL and a cytotoxic effect with a further increase in concentration. The effect of C-phycocyanin in the most effective concentration is comparable to the antioxidant effect of the mitochondria-targeted cation SkQ1.

Potent antioxidant alpha lipoic acid reduces STZ-induced oxidative stress and apoptosis levels in the erythrocytes and brain cells of diabetic rats

Diabetes, which causes oxidative stress-induced neuronal damage, is still one of the most important chronic health problems in the world. It can cause serious cellular loss and damage throughout the course of the disease. It is hypothesized that increased oxidative stress in this process increases free reactive oxygen species (ROS) and apoptotic markers and causes diabetic damage. Alpha-Lipoic acid (α-LA), which has a direct antioxidant effect in ROS reduction reactions, is also among the main components of the antioxidant system that works for free radical control and apoptosis. To understand the role of α-LA in reducing diabetes-induced oxidative damage, we examined the production of ROS in the brain cortex and erythrocytes of rats and their effects on markers of apoptosis. Forty adult Wistar albino rats were divided into four groups as control, α-LA, diabetic (DIA), and DIA+α-LA. For the induction of diabetes, the intraperitoneal injection of a dose of streptozotocin (STZ) (45 mg/kg) was used. α-LA (50 mg/kg) was applied to the groups of α-LA and DIA+α-LA for 14 days. At the end of the experiment, the brain cortex tissue and erythrocyte samples were taken from the rats. The levels of apoptosis, caspase 3, caspase 9, mitochondrial membrane potential, intracellular ROS, and lipid peroxidation were increased in the STZ group, although their levels were decreased in the DIA+α-LA group by the injection of α-LA. The STZ treatmentinduced decreases of cell viability, reduced glutathione, and glutathione peroxidase were increased in the brain and erythrocytes by the treatment of α-LA. In conclusion, diabetes acted a role in neuronal damage caused by increased ROS and apoptosis. We observed that α-LA induced a modulatory role on the apoptotic, oxidant, and antioxidant parameters in the brain and erythrocyte. The neuroprotective role of α-LA treatment may be explained by its modulating activity against increased oxidative stress and apoptosis.

Possibilities and prospects for antioxidant therapy in ocular diseases

The eye is particularly vulnerable to oxidative stress due to its constant exposure to atmospheric oxygen, sunlight, ultraviolet and ionizing radiation, chemicals, pollutants, and microorganisms that may shift the physiological balance towards oxidation. Today, oxidative stress is considered a major pathogenetic feature of a wide spectrum of ocular conditions including diseases of the lens (cataract), anterior chamber (glaucoma), cornea (keratoconus, traumatic injuries, post-operative conditions), eye surface (pterygium, dry eye syndrome), retina (uveitis, retinopathies), and optic nerve (optic neuropathies, glaucoma). Potential strategies for pathogenetic therapy in conditions, associated with oxidative stress, include direct inhibition of lipid peroxidation, induction of Nrf2 transcription factor signaling, repression and sequestration of vascular endothelial growth factor (VEGF), and the use of agents with direct antioxidant effect. Methylethylpyridinol or 3-oxy-6-methyl-2-ethylpyridine hydrochloride, a potent free radical scavenger, is often regarded as a major antioxidant agent for ophthalmological purposes. Methylethylpyridinol is characterized by a possibility of being used in different types of dosage forms. In ophthalmology, it is given by injection, as well as by instillation in the form of eye drops. Methylethylpyridinol can be used for the treatment and prevention of inflammation and burn injuries of the cornea, hemorrhages into the anterior chamber of the eye and into the sclera, thrombosis of the central retinal vein and its branches, diabetic retinopathy and complications in myopia, as well as for the protection of the cornea when exposed to high intensity light and wearing contact lenses. This paper reviews the main features of oxidative stress as the leading pathogenetic factor in ocular diseases, and the possibilities of antioxidant therapy using methylethylpyridinol.

Ameliorating Role of Hydrogen-Rich Water Against NSAID-Induced Enteropathy via Reduction of ROS and Production of Short-Chain Fatty Acids.

Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy, the mechanism of which is involved in oxidative stress, can be lethal due to hemorrhage. Thus, we aimed to investigate the effect of hydrogen-rich water (HRW), in terms of oxidative stress, on intestinal mucosal damage as well as changes in the gut microbiome and the short-chain fatty acids (SCFAs) content in feces. Hydrogen-rich water was orally administered for 5 days to investigate the effectiveness of indomethacin-induced enteropathy in mice. Small intestinal damage and luminal reactive oxygen species (ROS) were evaluated to investigate the ameliorating effects of hydrogen. Then, components of the gut microbiome were analyzed; fecal microbiota transplantation (FMT) was performed using the cecal contents obtained from mice drinking HRW. The cecal contents were analyzed for the SCFAs content. Finally, cells from the macrophage cell line RAW264 were co-cultured with the supernatants of cecal contents. Hydrogen-rich water significantly ameliorated IND-induced enteropathy histologically and reduced the expression of IND-induced inflammatory cytokines. Microscopic evaluation revealed that luminal ROS was significantly reduced and that HRW did not change the gut microbiota; however, FMT from HRW-treated animals ameliorated IND-induced enteropathy. The SCFA content in the cecal contents of HRW-treated animals was significantly higher than that in control animals. The supernatant had significantly increased interleukin-10 expression in RAW264 cells in vitro. Hydrogen-rich water ameliorated NSAID-induced enteropathy, not only via direct antioxidant effects but also via anti-inflammatory effects by increasing luminal SCFAs. These results suggest that hydrogen may have therapeutic potential in small intestinal inflammatory diseases.

Possibilities of combined intranasal drugs in the treatment of patients with rhinosinusitis

Rhinosinusitis – an inflammatory process in the nasal cavity and paranasal sinuses is a global problem of practical medicine, which remains relevant for many years. The most common cause of acute rhinosinusitis is a viral infection, only in 0.2–5 % of patients the disease is further complicated by the formation of a bacterial focus of inflammation. Treatment of patients withARS involves the use of etiotropic, pathogenetic and symptomatic therapy. National clinical guidelines consider the use of systemic and topical etiotropic drugs, intranasal glucocorticosteroids, topical decongestants, irrigation- elimination procedures, mucoactive therapy, standardized herbal medicine, drainage of the paranasal sinuses, antihistamines (with concomitant allergies) and some other activities. Local administration of drugs in patients with rhinosinusitis provides targeted delivery of the active substance to the pathological focus and the creation of its required concentration, the virtual absence of systemic action due to low absorption, as well as a favorable softening, moisturizing, enveloping effect of auxiliary components. One of these drugs is the combined nasal spray containing tuaminoheptane sulfate and acetylcysteine. The effectiveness and safety of the use of this combination has been demonstrated by the results of a fairly large amount of research. The mild and sufficiently long vasoconstrictive effect of tuaminoheptane sulfate, the direct mucolytic, antioxidant and anti-inflammatory effects of acetylcysteine and the high safety of this combination determine its therapeutic value in children from 6 years of age and adult patients with rhinitis and rhinosinusitis.

Effect of exercise-based cardiac rehabilitation on the ischemic threshold in patients with high-risk ischemic heart disease

Abstract Introduction Coronary artery disease is a complex condition and is not always resolved after an interventional or surgical procedure, due to the remaining obstructions in the coronary tree or the severity of the atherosclerosis, leaving anginal symptoms, ischemic threshold (IU) in the exercise, decreased cardiorespiratory fitness, and poor quality of life (QoL). Exercise-based cardiac rehabilitation programs (Ex-CRP) usually develop ischemic preconditioning mechanisms thanks to their direct anti-inflammatory, antioxidant, antithrombotic and coronary neovascularization effects, thus improving coronary reserve flow. We hypothesize that an Ex-CRP is capable of favorably impacting the UI in these patients. Therefore, the objective of this study is to evaluate the effects of an Ex-CRP on the UI in patients with high-risk ischemic heart disease. Methods Quasi-experimental study with 121 patients with ischemic threshold due to high-risk ischemic heart disease (with perfusion defects in nuclear medicine, complex coronary anatomy or partially revascularized) and presence of ischemic threshold in the exercise test. An Ex-CRP of 4–6 weeks duration was performed, consisting of supervised and monitored training concurrent with 30-minute aerobic exercise sessions at 70% of heart rate reserve, 3 times per week, supplemented with resistance exercise. and an educational understanding program for the control of risk factors and nutritional and psycho-emotional care. At the end of the program, a stress test was performed to compare the post-intervention effects and ischemic threshold was defined as the presence of angina or electrocardiographic changes of ischemia with negative ST-segment depression in 2 consecutive beats more than 80 ms from the J point. and in more than two contiguous leads. Results The 121 patients with ischemic threshold were 61±10 years old and 75% were male. On the other hand, 29.7% had a diagnosis of heart failure and an average LVEF of 53.1±12.9%. After Ex-CRP, an improvement was found in calculated VO2p (24.7±7.8 vs 34.23±7.5; p=0.000), METs at maximum effort from 7.06±2.15 to 9.78±1.14 (p<0.0001) and submaximal load in watts from 44±21.32 to 61±24.49; p<0.0001. 40.5% of the patients who were admitted with UI resolved it (absence of post-intervention ischemic diagnosis) after Ex-CRP and the remaining percentage with UI (59.5%) displaced it by 2.62 METs (p<0.0001). With this, the cardiovascular risk calculated by the Duke Score also decreased from −7 to −2 (p<0.0001), and the myocardial efficiency index improved from 8 to 6 (p<0.0001), strength (79±15 to 92±8%; p<0.0001) and QoL (65±17 vs 82±12; p<0.0001). Conclusions Ex-CRP had a significant effect on the resolution or displacement of the UI in patients with high-risk ischemic heart disease. In addition, it improved muscle strength, quality of life, myocardial efficiency, and reduced the cardiovascular risk index calculated by the Duke score. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Centro de Estudios e Investigaciόn FISICOL. Cúcuta, ColombiaCardioFit. CDMX, México

Cellular Antioxidant Effect of an Aronia Extract and Its Polyphenolic Fractions Enriched in Proanthocyanidins, Phenolic Acids, and Anthocyanins.

Oxidative stress and chronic inflammation contribute to some chronic diseases. Aronia berries are rich in polyphenols. The aim of the present study was to characterize the cellular antioxidant effect of an aronia extract to reflect the potential physiological in vivo effect. Cellular in vitro assays in three cell lines (Caco-2, HepG2, and SH-SY5Y) were used to measure the antioxidant effect of AE, in three enriched polyphenolic fractions (A1: anthocyanins and phenolic acids; A2: oligomeric proanthocyanidins; A3: polymeric proanthocyanidins), pure polyphenols and microbial metabolites. Both direct (intracellular and membrane radical scavenging, catalase-like effect) and indirect (NRF2/ARE) antioxidant effects were assessed. AE exerted an intracellular free radical scavenging activity in the three cell lines, and A2 and A3 fractions showed a higher effect in HepG2 and Caco-2 cells. AE also exhibited a catalase-like activity, with the A3 fraction having a significant higher activity. Only A1 fraction activated the NRF2/ARE pathway. Quercetin and caffeic acid are the most potent antioxidant polyphenols, whereas cyanidin and 5-(3′,4′-dihydroxyphenyl)-γ-valerolactone showed the highest antioxidant effect among polyphenol metabolites. AE rich in polyphenols possesses broad cellular antioxidant effects, and proanthocyanidins are major contributors. Polyphenol metabolites may contribute to the overall antioxidant effect of such extract in vivo.

Multi-Target Effects of ß-Caryophyllene and Carnosic Acid at the Crossroads of Mitochondrial Dysfunction and Neurodegeneration: From Oxidative Stress to Microglia-Mediated Neuroinflammation.

Inflammation and oxidative stress are interlinked and interdependent processes involved in many chronic diseases, including neurodegeneration, diabetes, cardiovascular diseases, and cancer. Therefore, targeting inflammatory pathways may represent a potential therapeutic strategy. Emerging evidence indicates that many phytochemicals extracted from edible plants have the potential to ameliorate the disease phenotypes. In this scenario, ß-caryophyllene (BCP), a bicyclic sesquiterpene, and carnosic acid (CA), an ortho-diphenolic diterpene, were demonstrated to exhibit anti-inflammatory, and antioxidant activities, as well as neuroprotective and mitoprotective effects in different in vitro and in vivo models. BCP essentially promotes its effects by acting as a selective agonist and allosteric modulator of cannabinoid type-2 receptor (CB2R). CA is a pro-electrophilic compound that, in response to oxidation, is converted to its electrophilic form. This can interact and activate the Keap1/Nrf2/ARE transcription pathway, triggering the synthesis of endogenous antioxidant “phase 2” enzymes. However, given the nature of its chemical structure, CA also exhibits direct antioxidant effects. BCP and CA can readily cross the BBB and accumulate in brain regions, giving rise to neuroprotective effects by preventing mitochondrial dysfunction and inhibiting activated microglia, substantially through the activation of pro-survival signalling pathways, including regulation of apoptosis and autophagy, and molecular mechanisms related to mitochondrial quality control. Findings from different in vitro/in vivo experimental models of Parkinson’s disease and Alzheimer’s disease reported the beneficial effects of both compounds, suggesting that their use in treatments may be a promising strategy in the management of neurodegenerative diseases aimed at maintaining mitochondrial homeostasis and ameliorating glia-mediated neuroinflammation.

Antioxidative Properties of Plant-Based Protein Isolates: NUTRALYS® Pea Protein

ObjectivesAntioxidants display protective benefits both in food and pharmaceutical products against oxidative deterioration and in the body against pathologies brought by oxidative stress. Proteins can contain peptides sequences with potential antioxidant bioactivities. As plant-based proteins sources are more and more consumed, the screening of their antioxidant properties is of great interest to provide new alternative solutions in place of synthetic antioxidants and to meet enhanced public awareness about health issues. Various in vitro methods are validated for screening and some have been used here to qualify the antioxidative potential of NUTRALYS® pea protein range (Roquette). MethodsTwo grades of pea protein isolates, NUTRALYS® S85F and NUTRALYS® S85 Plus, were screened before or after in vitro gastro-intestinal digestion (IVD) for their antioxidant activity with different methods: 1/reactive oxygen species (ROS) adapted scavenging assays (acellular) (Haliwell et al., 1987; Aruoma et al., 1989) to determine their ability to inhibit the productions of O2.-, H2O2 and HO. radicals; 2/AOP1 (LUCS) technology (Gironde et al., 2020), evaluating on human keratinocytes (HaCat cells) the ROS scavenging potential by the kinetic evolution of a fluorescence emission; 3/Nrf2 technology (Furger, 2021) measuring on HaCat cells the ability to activate the ARE/Nrf2 gene pathway, responsible for natural antioxidant cell defense (cytoprotective effect), by oxyluciferin luminescent detection. ResultsNUTRALYS® S85F and S85 Plus demonstrated significant scavenging activities towards HO. and H2O2 (before and after IVD) and NUTRALYS® S85F towards O2.- (before IVD), with all IC50 far below 5 mg.mL–1 (Dugardin et al., 2020). No significant direct antioxidant effect (LUCS) was observed with NUTRALYS® S85 Plus digests, but significant activation of the ARE/Nrf2 gene pathway (EC50 = 1.39 mg.mL-1 dry matter), indicating a potential induction of cell anticipation towards putative radical aggression, and a long-term effect. ConclusionsNUTRALYS® S85F and NUTRALYS® S85 Plus exhibit intrinsic antioxidative properties, often conserved after IVD, as observed through various methods. Based on these results, NUTRALYS® S85F and NUTRALYS® S85 Plus may therefore provide oxidative stability to food products and health benefits to the consumer. Funding SourcesRoquette.