Antioxidants, Volume 12, Issue 7 (July 2023) – 167 articles

In recent years, bone loss and its associated diseases have become a significant public health concern due to increased disability, morbidity, and mortality. Oxidative stress and bone loss are correlated, where oxidative stress suppresses osteoblast activity, resulting in compromised homeostasis between bone formation and resorption. This event causes upregulation of bone remodeling turnover rate with an increased risk of fractures and bone loss. Therefore, supplementation of antioxidants can be proposed to reduce oxidative stress, facilitate the bone remodeling process, suppress the initiation of bone diseases, and improve bone health. Astaxanthin (3,3′-dihydroxy-4-4′-diketo-β-β carotene), a potent antioxidant belonging to the xanthophylls family, is a potential ROS scavenger and could be a promising therapeutic nutraceutical possessing various pharmacological properties. In bone, astaxanthin enhances osteoblast differentiation, osteocytes numbers, and/or differentiation, inhibits osteoclast differentiation, cartilage degradation markers, and increases bone mineral density, expression of osteogenic markers, while reducing bone loss. In this review, we presented the up-to-date findings of the potential anabolic effects of astaxanthin on bone health in vitro, animal, and human studies by providing comprehensive evidence for its future clinical application, especially in treating bone diseases. Full article

Parkinson’s disease (PD) is a chronic and progressive neurodegenerative disorder characterized by a complex pathophysiology and a range of symptoms. The prevalence increases with age, putting the ageing population at risk. Disease management includes the improvement of symptoms, the comfort of the patient’s life, and palliative care. As there is currently no cure, growing evidence points towards the beneficial role of polyphenols on neurodegeneration. Numerous studies indicate the health benefits of the family of urolithins, especially urolithin A (UA). UA is a bacterial metabolite produced by dietary ellagitannins and ellagic acid. An expanding body of literature explores the involvement of the compound in mitochondrial health, and its anti-inflammatory, anti-oxidant, and anti-apoptotic properties. The review organizes the existing knowledge on the role of UA in health and diseases, emphasizing neurodegenerative diseases, especially PD. We gathered data on the potential neuroprotective effect in in vivo and in vitro models. We discussed the possible mechanisms of action of the compound and related health benefits to give a broader perspective of potential applications of UA in neuroprotective strategies. Moreover, we projected the future directions of applying UA in PD management. Full article

Morphine (MOR) is a commonly prescribed drug for the treatment of moderate to severe diabetic neuropathic pain (DNP). However, long-term MOR treatment is limited by morphine analgesic tolerance (MAT). The activation of microglial cells and the release of glia-derived proinflammatory cytokines are known to play an important role in the development of MAT. In this study, we aimed to investigate the effects of the dipeptidyl peptidase-4 inhibitor (DPP-4i) teneligliptin (TEN) on MOR-induced microglial cell activation and MAT in DNP rats. DNP was induced in four groups of male Wistar rats through a single intraperitoneal injection of streptozotocin (STZ) (50 mg/kg, freshly dissolved in 5 mmol/L citrate buffer, pH 4.5). Sham rats were administered with the vehicle. Seven days after STZ injection, all rats were implanted with an intrathecal (i.t) catheter connected to a mini-osmotic pump, divided into five groups, and infused with the following combinations: sham + saline (1 µL/h, i.t), DNP + saline (1 µL/h, i.t), DNP + MOR (15 µg/h, i.t), DNP + TEN (2 µg/h, i.t), and DNP + MOR (15 µg/h, i.t) + TEN (2 µg/h, i.t) for 7 days at a rate of 1 μL/h. The MAT was confirmed through the measurement of mechanical paw withdrawal threshold and tail-flick tests. The mRNA expression of neuroprotective proteins nuclear factor erythroid 2-related factor (Nrf2) and heme oxygenase-1 (HO-1) in the dorsal horn was evaluated by quantitative PCR (qPCR). Microglial cell activation and mononucleate cell infiltration in the spinal cord dorsal horn were assessed by immunofluorescence assay (IFA) and Western blotting (WB). The results showed that co-infusion of TEN with MOR significantly attenuated MAT in DNP rats through the restoration of neuroprotective proteins Nrf2 and HO-1 and suppression of microglial cell activation in the dorsal horn. Though TEN at a dose of 2 μg has mild antinociceptive effects, it is highly effective in limiting MAT. Full article

Aging is associated with a decline in mitochondrial function which may contribute to age-related diseases such as neurodegeneration, cancer, and cardiovascular diseases. Recently, mitochondrial Complex II has emerged as an important player in the aging process. Mitochondrial Complex II converts succinate to fumarate and plays an essential role in both the tricarboxylic acid (TCA) cycle and the electron transport chain (ETC). The dysfunction of Complex II not only limits mitochondrial energy production; it may also promote oxidative stress, contributing, over time, to cellular damage, aging, and disease. Intriguingly, succinate, the substrate for Complex II which accumulates during mitochondrial dysfunction, has been shown to have widespread effects as a signaling molecule. Here, we review recent advances related to understanding the function of Complex II, succinate signaling, and their combined roles in aging and aging-related diseases. Full article

Clostridium perfringens causes necrotic enteritis (NE) after proliferation in the intestine of poultry, resulting in considerable losses to the poultry industry. This study aimed to investigate the impact of tannic acid on the antioxidant, immunity, and gut health of broilers with NE. In the experiment, 630 one-day-old Cobb500 male chicks were randomly divided into six treatment groups, with seven replicate cages and with fifteen birds in each cage. The treatment groups were as follows: control group (NC), challenged group (PC), and challenged NE chickens treated with 250, 500, 750, and 1000 mg/kg tannic acid (PTA1, PTA2, PTA3, and PTA4, respectively). To induce NE, coccidia vaccine and Clostridium perfringens were administered on day 19 and days 22–28, respectively. Indexes related to antioxidant, immune, and intestinal health were measured on days 28 and 35. During the infection period, we observed significant increases in fecal water content, D-LA, TNF-α, and malondialdehyde concentrations (p < 0.05). Conversely, significant decreases were noted in chyme pH and in T-AOC, IL-4, and IL-10 concentrations (p < 0.05). The addition of tannic acid exhibited a linear decrease in fecal water content and TNF-α concentration (p < 0.05). Furthermore, tannic acid supplementation resulted in a quadratic curve decrease in D-LA concentration and linear increases in T-AOC, IL-4, and IL-10 (p < 0.05). Cecal microbiological analysis revealed that Ruminococcaceae and Butyricimona were dominant in PTA3. In conclusion, the dietary addition of tannic acid may reduce the negative effects of NE by increasing antioxidant and anti-inflammatory capacity, improving the intestinal barrier, and regulating the intestinal flora. Full article

Fruit thinning is a common practice employed to enhance the quality and yield of kiwifruits during the growing period, and about 30–50% of unripe kiwifruits will be thinned and discarded. In fact, these unripe kiwifruits are rich in nutrients and bioactive compounds. Nevertheless, the applications of thinned young kiwifruits and related bioactive compounds in the food and functional food industry are still limited. Therefore, to promote the potential applications of thinned young kiwifruits as value-added health products, the extraction, characterization, and evaluation of beneficial effects of phenolic compounds from thinned young fruits of red-fleshed Actinidia chinensis cv ‘HY’ were examined in the present study. A green and efficient ultrasound-assisted deep eutectic solvent extraction (UADE) method for extracting phenolic compounds from thinned young kiwifruits was established. A maximum yield (105.37 ± 1.2 mg GAE/g DW) of total phenolics extracted from thinned young kiwifruits by UADE was obtained, which was significantly higher than those of conventional organic solvent extraction (CSE, about 14.51 ± 0.26 mg GAE/g DW) and ultrasound-assisted ethanol extraction (UAEE, about 43.85 ± 1.17 mg GAE/g DW). In addition, 29 compounds, e.g., gallic acid, chlorogenic acid, neochlorogenic acid, catechin, epicatechin, procyanidin B1, procyanidin B2, quercetin-3-rhamnoside, and quercetin-3-O-glucoside, were identified in the kiwifruit extract by UPLC-MS/MS. Furthermore, the contents of major phenolic compounds in different kiwifruit extracts prepared by conventional organic solvent extraction (EE), ultrasound-assisted ethanol extraction (UEE), and ultrasound-assisted deep eutectic solvent extraction (UDE) were compared by HPLC analysis. Results revealed that the content of major phenolics in UDE (about 15.067 mg/g DW) was significantly higher than that in EE (about 2.218 mg/g DW) and UEE (about 6.122 mg/g DW), suggesting that the UADE method was more efficient for extracting polyphenolics from thinned young kiwifruits. In addition, compared with EE and UEE, UDE exhibited much higher antioxidant and anti-inflammatory effects as well as inhibitory effects against α-glucosidase and pancreatic lipase, which were closely associated with its higher content of phenolic compounds. Collectively, the findings suggest that the UADE method can be applied as an efficient technique for the preparation of bioactive polyphenolics from thinned young kiwifruits, and the thinned young fruits of red-fleshed A. chinensis cv ‘HY’ have good potential to be developed and utilized as functional foods and nutraceuticals. Full article

Muscle fatigue is a common symptom induced by exercise. A reversible loss of muscle force is observed with variable rates of recovery depending on the causes or underlying mechanisms. It can not only affect locomotion muscles, but can also affect the heart, in particular after intense prolonged exercise such as marathons and ultra-triathlons. The goal of our study was to explore the effect of four different natural extracts with recognized antioxidant properties on the contractile function of skeletal (locomotion) and cardiac muscles after a prolonged exhausting exercise. Male Wistar rats performed a bout of exhausting exercise on a treadmill for about 2.5 h and were compared to sedentary animals. Some rats received oral treatment of a natural extract (rosemary, buckwheat, Powergrape^®, or rapeseed) or the placebo 24 h and 1 h before exercise. Experiments were performed 30 min after the race and after 7 days of recovery. All natural extracts had protective effects both in cardiac and skeletal muscles. The extent of protection was different depending on muscle type and the duration post-exercise (just after and after one-week recovery), including antiarrhythmic effect and anti-diastolic dysfunction for the heart, and faster recovery of contractility for the skeletal muscles. Moreover, the muscular protective effect varied between natural extracts. Our study shows that an acute antioxidant supplementation can protect against acute abnormal endogenous ROS toxicity, induced here by prolonged exhausting exercise. Full article

A novel antioxidant containing four hydroxyl groups, namely 2,2′-(2-methylpropane-1,3-diyl)bis(hydroquinone) (MPBHQ), was synthesized using hydroquinone and methylallyl alcohol as the raw materials, phosphoric acid as the catalyst, and toluene as the solvent system. The structure of MPBHQ was characterized by mass spectrometry, nuclear magnetic resonance, ultraviolet spectroscopy, and infrared spectroscopy. The results showed that MPBHQ has a good radical scavenging effect, as measured by the ORAC assay, DPPH radical scavenging assay, ABST radical scavenging assay, and Rancimat test. In fatty acid methyl ester and lard without exogenous antioxidants, MPBHQ showed better antioxidant performance than butylated hydroxytoluene (BHT), hydroquinone (HQ), tert-butyl hydroquinone (TBHQ), and propyl gallate (PG), meeting the need for a new antioxidant with better properties to ensure the oxidative stability of lipids and biodiesel. Full article

Epidemiological studies have shown that consuming olive oil rich in phenolic bioactive compounds is associated with a lower risk of neurodegenerative diseases and better cognitive performance in aged populations. Since oxidative stress is a common hallmark of age-related cognitive decline, incorporating exogenous antioxidants could have beneficial effects on brain aging. In this review, we firstly summarize and critically discuss the current preclinical evidence and the potential neuroprotective mechanisms. Existing studies indicate that olive oil phenolic compounds can modulate and counteract oxidative stress and neuroinflammation, two relevant pathways linked to the onset and progression of neurodegenerative processes. Secondly, we summarize the current clinical evidence. In contrast to preclinical studies, there is no direct evidence in humans of the bioactivity of olive oil phenolic compounds. Instead, we have summarized current findings regarding nutritional interventions supplemented with olive oil on cognition. A growing body of research indicates that high consumption of olive oil phenolic compounds is associated with better preservation of cognitive performance, conferring an additional benefit, independent of the dietary pattern. In conclusion, the consumption of olive oil rich in phenolic bioactive compounds has potential neuroprotective effects. Further research is needed to understand the underlying mechanisms and potential clinical applications. Full article

Ketone bodies (KBs) are an alternative energy source under starvation and play multiple roles as signaling molecules regulating energy and metabolic homeostasis. The mechanism by which KBs influence visceral white adipose tissue physiology is only partially known, and our study aimed to shed light on the effects they exert on such tissue. To this aim, we administered 1,3-butanediol (BD) to rats since it rapidly enhances β-hydroxybutyrate serum levels, and we evaluated the effect it induces within 3 h or after 14 days of treatment. After 14 days of treatment, rats showed a decrease in body weight gain, energy intake, gonadal-WAT (gWAT) weight, and adipocyte size compared to the control. BD exerted a pronounced antioxidant effect and directed redox homeostasis toward reductive stress, already evident within 3 h after its administration. BD lowered tissue ROS levels and oxidative damage to lipids and proteins and enhanced tissue soluble and enzymatic antioxidant capacity as well as nuclear erythroid factor-2 protein levels. BD also reduced specific mitochondrial maximal oxidative capacity and induced endoplasmic reticulum stress as well as interrelated processes, leading to changes in the level of adipokines/cytokines involved in inflammation, macrophage infiltration into gWAT, adipocyte differentiation, and lipolysis. Full article

Vitamins, hormones, free radicals, and antioxidant substances significantly influence athletic performance. The aim of this study was to evaluate whether these biological mediators changed during the season and if this was associated with the rate of improvement in performance after training, assessed by means of a standardized test. Professional male soccer players took part in the study. Two evaluations were performed: the first in the pre-season period and the second at the mid-point of the official season, after about 6 months of intensive training and weekly matches. Blood levels of vitamins D, B12, and folic acid, testosterone and cortisol, free radicals, and antioxidant substances were measured. Two hours after breakfast, a Yo-Yo test was performed. The relationships between the biological mediators and the rate of improvement after training (i.e., the increase in meters run in the Yo-Yo test between the pre-season and mid-season periods) were evaluated by means of a linear mixed models analysis. Results: Eighty-two paired tests were performed. The athletes showed better performance after training, with an increase in the meters run of about 20%. No significant relationships between the vitamin and hormone values and the gain in the performance test were observed. Plasmatic levels of free radicals increased significantly, as did the blood antioxidant potential. An indirect relationship between oxidative stress and the improvement in performance was observed (free radicals β ± SE: = −0.33 ± 0.10; p-value = 0.001), with lower levels of oxidative stress being associated with higher levels of performance in the Yo-Yo test. Monitoring the measures of oxidative stress could be a useful additional tool for coaches in training and/or recovery programs tailored to each player. Full article

Originally identified as a key component of the mitochondrial respiratory chain, Coenzyme Q (CoQ or CoQ₁₀ for human tissues) has recently been revealed to be essential for many different redox processes, not only in the mitochondria, but elsewhere within other cellular membrane types. Cells rely on endogenous CoQ biosynthesis, and defects in this still-not-completely understood pathway result in primary CoQ deficiencies, a group of conditions biochemically characterised by decreased tissue CoQ levels, which in turn are linked to functional defects. Secondary CoQ deficiencies may result from a wide variety of cellular dysfunctions not directly linked to primary synthesis. In this article, we review the current knowledge on CoQ biosynthesis, the defects leading to diminished CoQ₁₀ levels in human tissues and their associated clinical manifestations. Full article

Malaria is still the most important parasitic infectious disease. Numerous substances are known to have antimalarial activity; among them, artemisinin is the most widely used one, and artemisinin-based combination therapy (ACT) is recommended for the treatment of Plasmodium falciparum (P.f.) malaria. Antitumor, immunomodulatory, and other therapeutic applications of artemisinin are under extensive study. Several different mechanisms of action were proposed for dihydroartemisinin (DHA), the active metabolite of artemisinin, such as eliciting oxidative stress in target cells. The goal of this study is to monitor the generation of reactive oxygen species (ROS) and lipid peroxidation product 4-hydroxynonenal (4-HNE) by DHA in P.f.-infected human erythrocytes. Checking ROS and 4-HNE-protein adducts kinetics along the maturation of the parasite, we detected the highest level of 4-HNE in ring forms of P.f. due to DHA treatment. Low micromolar concentrations of DHA quickly induced levels of 4-HNE-adducts which are supposed to be damaging. Mass spectrometry identified the P.f. protein cysteine proteinase falcipain-1 as being heavily modified by 4-HNE, and plausibly, 4-HNE conjugation with vital P.f. proteins might contribute to DHA-elicited parasite death. In conclusion, significant 4-HNE accumulation was detectable after DHA treatment, though, at concentrations well above pharmacologically effective ranges in malaria treatment, but at concentrations described for antitumor activity. Thus, lipid peroxidation with consequent 4-HNE conjugation of functionally relevant proteins might be considered as a uniform mechanism for how DHA potentiates antimalarials’ action in ACT and controls the progression of tumors. Full article

Berberis vulgaris L. is currently widely studied for its antioxidant and chemopreventive properties, especially with regard to the beneficial properties of its fruits. Although the bark and roots have been well known and used in traditional medicine since ancient times, little is known about the other parts of this plant. The aim of the research was to determine the antioxidant and LOX inhibitory activity effects of extracts obtained from the leaves, fruits, and stems. Another aim of the work was to carry out the quantitative and qualitative analysis of phenolic acids, flavonoid aglycones, and flavonoid glycosides. The extracts were obtained with the use of ASE (accelerated solvent extraction). The total content of polyphenols was determined and was found to vary depending on the organ, with the highest amount of polyphenols found in the leaf extracts. The free radical scavenging activity of the extracts was determined spectrophotometrically in relation to the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical, with results ranging from 63.9 mgTE/g for the leaves to 65.2 mgTE/g for the stem. Antioxidant activity was also assessed using the ABTS test. The lowest value was recorded for the barberry fruit (117.9 mg TE/g), and the highest level was found for the barberry leaves (140.5 mgTE/g). The oxygen radical absorbance capacity test (ORAC) showed the lowest value for the stem (167.7 mgTE/g) and the highest level for the leaves (267.8 mgTE/g). The range of the percentage inhibition of LOX was determined as well. The percentage inhibition of the enzyme was positively correlated with the sum of the flavonoids, TPC, TFC, and the content of selected flavonoids. Phenolic acids, flavonoid aglycones, and flavonoid glycosides were determined qualitatively and quantitatively in individual parts of Berberis vulgaris L. The content of phenolic acids, flavonoid aglycones, and flavonoid glycosides was determined with the LC-MS/MS method. The following phenolic acids were quantitatively and qualitatively identified in individual parts of Berberis vulgaris L.: gallic acid, 3-caffeoylquinic acid, protocatechuic acid, 5-caffeoylquinic acid, 4-caffeoylquinic acid, and caffeic acid. The flavonoid glycosides determined were: eleutheroside E, Eriodictyol-7-glucopyranoside, rutin, hyperoside, isoquercitin, luteoloside, narcissoside, naringenin-7-glucoside, isorhamnetin-3-glucoside, afzeline, and quercitrin. Flavonoid aglycones such as catechin, luteolin, quercetin, and eriodictyol were also determined qualitatively and quantitatively. Full article

Diabetic retinopathy (DR) is a complication of diabetes mellitus that can lead to vision loss and blindness. It is driven by various biochemical processes and molecular mechanisms, including lipid peroxidation and disrupted aldehyde metabolism, which contributes to retinal tissue damage and the progression of the disease. The elimination and processing of aldehydes in the retina rely on the crucial role played by aldehyde dehydrogenase (ALDH) and aldo-keto reductase (AKR) enzymes. This review article investigates the impact of oxidative stress, lipid-derived aldehydes, and advanced lipoxidation end products (ALEs) on the advancement of DR. It also provides an overview of the ALDH and AKR enzymes expressed in the retina, emphasizing their growing importance in DR. Understanding the relationship between aldehyde metabolism and DR could guide innovative therapeutic strategies to protect the retina and preserve vision in diabetic patients. This review, therefore, also explores various approaches, such as gene therapy and pharmacological compounds that have the potential to augment the expression and activity of ALDH and AKR enzymes, underscoring their potential as effective treatment options for DR. Full article

Optic nerve disorders encompass a wide spectrum of conditions characterized by the loss of retinal ganglion cells (RGCs) and subsequent degeneration of the optic nerve. The etiology of these disorders can vary significantly, but emerging research highlights the crucial role of oxidative stress, an imbalance in the redox status characterized by an excess of reactive oxygen species (ROS), in driving cell death through apoptosis, autophagy, and inflammation. This review provides an overview of ROS-related processes underlying four extensively studied optic nerve diseases: glaucoma, Leber’s hereditary optic neuropathy (LHON), anterior ischemic optic neuropathy (AION), and optic neuritis (ON). Furthermore, we present preclinical findings on antioxidants, with the objective of evaluating the potential therapeutic benefits of targeting oxidative stress in the treatment of optic neuropathies. Full article

Quinones can in principle be viewed as a double-edged sword in the treatment of neurodegenerative diseases, since they are often cytoprotective but can also be cytotoxic due to covalent and redox modification of biomolecules. Nevertheless, low doses of moderately electrophilic quinones are generally cytoprotective, mainly due to their ability to activate the Keap1/Nrf2 pathway and thus induce the expression of detoxifying enzymes. Some natural quinones have relevant roles in important physiological processes. One of them is coenzyme Q₁₀, which takes part in the oxidative phosphorylation processes involved in cell energy production, as a proton and electron carrier in the mitochondrial respiratory chain, and shows neuroprotective effects relevant to Alzheimer’s and Parkinson’s diseases. Additional neuroprotective quinones that can be regarded as coenzyme Q₁₀ analogues are idobenone, mitoquinone and plastoquinone. Other endogenous quinones with neuroprotective activities include tocopherol-derived quinones, most notably vatiquinone, and vitamin K. A final group of non-endogenous quinones with neuroprotective activity is discussed, comprising embelin, APX-3330, cannabinoid-derived quinones, asterriquinones and other indolylquinones, pyrroloquinolinequinone and its analogues, geldanamycin and its analogues, rifampicin quinone, memoquin and a number of hybrid structures combining quinones with amino acids, cholinesterase inhibitors and non-steroidal anti-inflammatory drugs. Full article

Parkinson’s disease (PD) is a neurodegenerative disorder involving motor symptoms caused by a loss of dopaminergic neurons in the substantia nigra region of the brain. Epidemiological evidence suggests that anthocyanin (ANC) intake is associated with a low risk of PD. Previously, we reported that extracts enriched with ANC and proanthocyanidins (PAC) suppressed dopaminergic neuron death elicited by the PD-related toxin rotenone in a primary midbrain culture model. Here, we characterized botanical extracts enriched with a mixed profile of polyphenols, as well as a set of purified polyphenolic standards, in terms of their ability to mitigate dopaminergic cell death in midbrain cultures exposed to another PD-related toxicant, paraquat (PQ), and we examined underlying neuroprotective mechanisms. Extracts prepared from blueberries, black currants, grape seeds, grape skin, mulberries, and plums, as well as several ANC, were found to rescue dopaminergic neuron loss in PQ-treated cultures. Comparison of a subset of ANC-rich extracts for the ability to mitigate neurotoxicity elicited by PQ versus rotenone revealed that a hibiscus or plum extract was only neuroprotective in cultures exposed to rotenone or PQ, respectively. Several extracts or compounds with the ability to protect against PQ neurotoxicity increased the activity of the antioxidant transcription factor Nrf2 in cultured astrocytes, and PQ-induced dopaminergic cell death was attenuated in Nrf2-expressing midbrain cultures. In other studies, we found that extracts prepared from hibiscus, grape skin, or purple basil (but not plums) rescued defects in O₂ consumption in neuronal cells treated with rotenone. Collectively, these findings suggest that extracts enriched with certain combinations of ANC, PAC, stilbenes, and other polyphenols could potentially slow neurodegeneration in the brains of individuals exposed to PQ or rotenone by activating cellular antioxidant mechanisms and/or alleviating mitochondrial dysfunction. Full article

Although the benefits of moderate exercise in patients at high cardiovascular risk are well established, the effects of strenuous exercise remain unknown. We aimed to study the impact of strenuous exercise in a very high cardiovascular risk model. Nephrectomized aged Zucker obese rats were trained at a moderate (MOD) or high (INT) intensity or were kept sedentary (SED) for 10 weeks. Subsequently, echocardiography and ex vivo vascular reactivity assays were performed, and blood, aortas, perivascular adipose tissue (PVAT), and left ventricles (LVs) were harvested. An improved risk profile consisting of decreased body weight and improved response to a glucose tolerance test was noted in the trained groups. Vascular reactivity experiments in the descending thoracic aorta demonstrated increased endothelial NO release in the MOD group but not in the INT group, compared with SED; the free radical scavenger TEMPOL improved endothelial function in INT rats to a similar level as MOD. An imbalance in the expression of oxidative stress-related genes toward a pro-oxidant environment was observed in the PVAT of INT rats. In the heart, INT training promoted eccentric hypertrophy and a mild reduction in ejection fraction. Obesity was associated with LV fibrosis and a transition toward β-myosin heavy chain and the N2Ba titin isoform. Exercise reverted the myosin imbalance, but only MOD reduced the predominance of the N2Ba titin isoform. In conclusion, moderate exercise yields the most intense cardiovascular benefits in a high-cardiovascular-risk animal model, while intense training partially reverts them. Full article

Cancer is considered one of the main causes of human death worldwide, being characterized by an alteration of the oxidative metabolism. Many natural compounds from plant origin with anti-tumor attributes have been described. Among them, capsaicin, which is the molecule responsible for the pungency in hot pepper fruits, has been reported to show antioxidant, anti-inflammatory, and analgesic activities, as well as anti-proliferative properties against cancer. Thus, in this work, the potential anti-proliferative activity of pepper (Capsicum annuum L.) fruits from diverse varieties with different capsaicin contents (California < Piquillo < Padrón < Alegría riojana) against several tumor cell lines (lung, melanoma, hepatoma, colon, breast, pancreas, and prostate) has been investigated. The results showed that the capsaicin content in pepper fruits did not correspond with their anti-proliferative activity against tumor cell lines. By contrast, the greatest activity was promoted by the pepper tissues which contained the lowest capsaicin amount. This indicates that other compounds different from capsaicin have this anti-tumor potentiality in pepper fruits. Based on this, green fruits from the Alegría riojana variety, which has negligible capsaicin levels, was used to study the effect on the oxidative and redox metabolism of tumor cell lines from liver (Hep-G2) and pancreas (MIA PaCa-2). Different parameters from both lines treated with crude pepper fruit extracts were determined including protein nitration and protein S-nitrosation (two post-translational modifications (PTMs) promoted by nitric oxide), the antioxidant capacity, as well as the activity of the antioxidant enzymes superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPX), among others. In addition, the activity of the NADPH-generating enzymes glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconate dehydrogenase (6PGDH), and NADP-isocitrate dehydrogenase (NADP-ICDH) was followed. Our data revealed that the treatment of both cell lines with pepper fruit extracts altered their antioxidant capacity, enhanced their catalase activity, and considerably reduced the activity of the NADPH-generating enzymes. As a consequence, less H₂O₂ and NADPH seem to be available to cells, thus avoiding cell proliferation and possibly triggering cell death in both cell lines. Full article

Alzheimer’s disease (AD) is the most common cause of dementia, characterised by a marked decline of both memory and cognition, along with pathophysiological hallmarks including amyloid beta peptide (Aβ) accumulation, tau protein hyperphosphorylation, neuronal loss and inflammation in the brain. Additionally, oxidative stress caused by an imbalance between free radicals and antioxidants is considered one of the main risk factors for AD, since it can result in protein, lipid and nucleic acid damage and exacerbate Aβ and tau pathology. To date, there is a lack of successful pharmacological approaches to cure or even ameliorate the terrible impact of this disease. Due to this, dietary compounds with antioxidative and anti-inflammatory properties acquire special relevance as potential therapeutic agents. In this context, green tea, and its main bioactive compound, epigallocatechin-3-gallate (EGCG), have been targeted as a plausible option for the modulation of AD. Specifically, EGCG acts as an antioxidant by regulating inflammatory processes involved in neurodegeneration such as ferroptosis and microglia-induced cytotoxicity and by inducing signalling pathways related to neuronal survival. Furthermore, it reduces tau hyperphosphorylation and aggregation and promotes the non-amyloidogenic route of APP processing, thus preventing the formation of Aβ and its subsequent accumulation. Taken together, these results suggest that EGCG may be a suitable candidate in the search for potential therapeutic compounds for neurodegenerative disorders involving inflammation and oxidative stress, including Alzheimer’s disease. Full article

Prolonged hyperglycemia related to diabetes and its complications leads to multiple cellular disorders, the central one being the dysfunction of mitochondria. Voltage-dependent anion channels (VDAC) of the outer mitochondrial membrane control the metabolic, ionic, and energy cross-talk between mitochondria and the rest of the cell and serve as the master regulators of mitochondrial functions. Here, we have investigated the effect of pharmacological suppression of VDAC1 by the newly developed inhibitor of its oligomerization, VBIT-4, in the primary culture of mouse lung endotheliocytes and downregulated expression of VDAC1 in human skin fibroblasts on the progression of mitochondrial dysfunction upon hyperglycemic stress. The cells were grown in high-glucose media (30 mM) for 36 h. In response to hyperglycemia, the mRNA level of VDAC1 increased in endotheliocytes and decreased in human skin fibroblasts. Hyperglycemia induced overproduction of mitochondrial ROS, an increase in the susceptibility of the organelles to mitochondrial permeability transition (MPT) pore opening and a drop in mitochondrial membrane potential, which was accompanied by a decrease in cell viability in both cultures. Treatment of endotheliocytes with 5 µM VBIT-4 abolished the hyperglycemia-induced increase in susceptibility to spontaneous opening of the MPT pore and ROS generation in mitochondria. Silencing of VDAC1 expression in human skin fibroblasts exposed to high glucose led to a less pronounced manifestation of all the signs of damage to mitochondria. Our data identify a mitochondria-related response to pharmacological and genetic suppression of VDAC activity in vascular cells in hyperglycemia and suggest the potential therapeutic value of targeting these channels for the treatment of diabetic vasculopathies. Full article

Olive oil and lycopene are foods that have potent antioxidant activity. The objective was to determine the effects of consumption of olive oil enriched with lycopene on oxidative stress biomarkers in hypercholesterolemic subjects. We examined the effects of oil enriched with lycopene extract daily intake during 1 month on plasma antioxidant capacity, lipids profile (triacylgycerols, total cholesterol, cHDL; cLDL, ox-LDL), biomarkers of oxidative stress, and inflammatory markers related with atherosclerosis risk (C-reactive protein (CRP), IL-6; sDC4L) in subjects hypercholesteremics (cholesterol > 220 mg/dL). In the group consuming olive oil-lycopene, significant increases (p < 0.05) in the levels of plasma lycopene concentration (0.146 ± 0.03 versus 0.202 ± 0.04 (µmol/L)), α-carotene (0.166 ± 0.064 versus 0.238 ± 0.07) and in β-carotene (0.493 ± 0.187 versus 0.713 ± 0.221) were observed. These results are linked with the increases of plasma antioxidants and decreases biomarkers of oxidative stress (carbonyl groups, malondialdehyde and 8-hydroxy-deoxiguanosine) observed in hypercholesterolemic group. In relation to lipid profile, a significant decrease was observed in the levels of ox-LDL (781 ± 302 versus 494 ± 200), remaining unchanged the levels of TG, cholesterol, HDL and LDL-c. Regarding inflammatory biomarkers, the levels of CRP and IL-6 decreased significantly. The positive results obtained in this study support the use of olive oil enriched with lycopene to reduce the risk of coronary disease. Full article

The resurgence of mead, a honey-based fermented beverage, is attributed to the increasing consumption of fermented foods and beverages, driven by its distinct flavors and perceived health benefits. This study investigates the influence of different yeast strains, namely Saccharomyces cerevisiae var. bayanus, and Torulaspora delbrueckii, on the volatile and phenolic compounds of these beverages. Analytical techniques, including HPLC-DAD and GS/MS, were employed to analyze the chemical composition of the beverages. ANOVA analysis of variance was conducted to assess differences in the volatile and phenolic compounds. The findings reveal that yeast selection significantly impacts the chemical profiles of the beverages. Saccharomyces cerevisiae fermentation preserves rosehip-specific flavonoids and phenolic acids. Sequential fermentation with Torulaspora delbrueckii demonstrated proficiency in generating esters, contributing to fruity and floral aromas in the beverages. This study investigates the importance of yeast selection in shaping the chemical composition of rosehip mead, providing insights into the distinct characteristics conferred by different yeast strains. By optimizing yeast selection and fermentation techniques, the overall quality and diversity of these beverages can be enhanced. Full article

In recent years, there has been a growing interest in utilizing natural antioxidants as alternatives to synthetic additives in food products. Apples and apple by-products have gained attention as a potential source of natural antioxidants due to their rich phenolic content. However, the extraction techniques applied for the recovery of phenolic compounds need to be chosen carefully. Studies show that ultrasound-assisted extraction is the most promising technique. High yields of phenolic compounds with antioxidant properties have been obtained by applying ultrasound on both apples and their by-products. Promising results have also been reported for green technologies such as supercritical fluid extraction, especially when a co-solvent is used. Once extracted, recent studies also indicate the feasibility of using these compounds in food products and packaging materials. The present review aims to provide a comprehensive overview of the antioxidant properties of apples and apple by-products, their extraction techniques, and potential applications in food products because of their antioxidant or nutritional properties. The findings reported here highlight the proper utilization of apples and their by-products in food to reduce the detrimental effect on the environment and provide a positive impact on the economy. Full article

Due to the growing awareness of the importance of healthy eating in society, there is an increasing interest in the use of herbs and low-processed, natural products. Ginkgo biloba is a raw material with a high pro-health potential, which is related to the high content of antioxidant compounds. The aim of the study was to determine the relationship between the antioxidant activity of Ginkgo biloba leaf infusions and the weighted amount of leaves and brewing time. In addition, a sensory analysis of the infusions obtained was carried out. The innovation is to determine the migration of micro- and macroelements to the infusion prepared from Ginkgo biloba depending on the leaves’ weight used and the brewing time. The research showed the dependence of the antioxidant activity of the infusions and the migration of microelements on the size of the dried material and the brewing time. In the publication, the main factors influencing the quality of infusions were analysed, their mutual correlations were determined, and combinations showing the highest antioxidant activity and, at the same time, the highest sensory acceptability were selected. Full article

Statins have been proposed for L-DOPA-induced dyskinesia (LID) treatment. Statin anti-dyskinetic effects were related to the inhibition of the Ras-ERK pathway. However, the mechanisms responsible for the anti-LID effect are unclear. Changes in cholesterol homeostasis and oxidative stress- and inflammation-related mechanisms such as angiotensin II and Rho-kinase (ROCK) inhibition may be involved. The nigra and striatum of dyskinetic rats showed increased levels of cholesterol, ROCK, and the inflammatory marker IL-1β, which were reduced by the angiotensin type-1 receptor (AT1) antagonist candesartan, simvastatin, and the ROCK inhibitor fasudil. As observed for LID, angiotensin II-induced, via AT1, increased levels of cholesterol and ROCK in the rat nigra and striatum. In cultured dopaminergic neurons, angiotensin II increased cholesterol biosynthesis and cholesterol efflux without changes in cholesterol uptake. In astrocytes, angiotensin induced an increase in cholesterol uptake, decrease in biosynthesis, and no change in cholesterol efflux, suggesting a neuronal accumulation of cholesterol that is reduced via transfer to astrocytes. Our data suggest mutual interactions between angiotensin/AT1, cholesterol, and ROCK pathways in LID, which are attenuated by the corresponding inhibitors. Interestingly, these three drugs have also been suggested as neuroprotective treatments against Parkinson’s disease. Therefore, they may reduce dyskinesia and the progression of the disease using common mechanisms. Full article

The demand for healthy ready-to-eat foods like snacks is increasing. Physical modification of vegetal food matrices through extrusion generates significant changes in the chemical composition of the final product. There is a great variety of food matrices that can be used in extrusion, most of them being based on cereals, legumes, fruits, vegetables, or seeds. The aim of this review was to summarize the main effects of the extrusion process on the bioactive compounds content, namely phenolics, terpenes, vitamins, minerals, and fibers of vegetal mixes, as well as on their biological activity. The literature reported contradictory results regarding the changes in bioactive compounds after extrusion, mainly due to the differences in the processing conditions, chemical composition, physicochemical properties, and nutritional value of the extruded material and quantification methods. The thermolabile phenolics and vitamins were negatively affected by extrusion, while the fiber content was proved to be enhanced. Further research is needed regarding the interactions between bioactive components during extrusion, as well as a more detailed analysis of the impact of extrusion on the terpenes since there are few papers dealing with this aspect. Full article

Honey bee products comprise various compounds, including honey, propolis, royal jelly, bee pollen, bee wax and bee venom, which have long been recognized for their pharmacological and health-promoting benefits. Scientists have discovered that periodontal disorders stem from dental biofilm, an inflammatory response to bacterial overgrowth produced by dysbiosis in the oral microbiome. The bee products have been investigated for their role in prevention of oral diseases, which are attributed to a myriad of biologically active compounds including flavonoids (pinocembrin, catechin, caffeic acid phenethyl ester (CAPE) and galangin), phenolic acids (hydroxybenzoic acid, hydroxycinnamic acid, p-coumaric, ellagic, caffeic and ferulic acids) and terpenoids. This review aims to update the current understanding of role of selected bee products, namely, honey, propolis and royal jelly, in preventing oral diseases as well as their potential biological activities and mechanism of action in relation to oral health have been discussed. Furthermore, the safety of incorporation of bee products is also critically discussed. To summarize, bee products could potentially serve as a therapy option for people suffering from a variety of oral disorders. Full article

Adventitious root (AR) formation is a critical process in cutting propagation of horticultural plants. Brassinosteroids (BRs) have been shown to regulate AR formation in several plant species; however, little is known about their exact effects on pepper AR formation, and the downstream signaling of BRs also remains elusive. In this study, we showed that treatment of 24-Epibrassinolide (EBL, an active BR) at the concentrations of 20–100 nM promoted AR formation in pepper (Capsicum annuum). Furthermore, we investigated the roles of apoplastic reactive oxygen species (ROS), including hydrogen peroxide (H₂O₂) and superoxide radical (O₂^•−), in EBL-promoted AR formation, by using physiological, histochemical, bioinformatic, and biochemical approaches. EBL promoted AR formation by modulating cell-wall-located polyamine oxidase (PAO)-dependent H₂O₂ production and respiratory burst oxidase homologue (RBOH)-dependent O₂^•− production, respectively. Screening of CaPAO and CaRBOH gene families combined with gene expression analysis suggested that EBL-promoted AR formation correlated with the upregulation of CaPAO1, CaRBOH2, CaRBOH5, and CaRBOH6 in the AR zone. Transient expression analysis confirmed that CaPAO1 was able to produce H₂O₂, and CaRBOH2, CaRBOH5, and CaRBOH6 were capable of producing O₂^•−. The silencing of CaPAO1, CaRBOH2, CaRBOH5, and CaRBOH6 in pepper decreased the ROS accumulation and abolished the EBL-induced AR formation. Overall, these results uncover one of the regulatory pathways for BR-regulated AR formation, and extend our knowledge of the functions of BRs and of the BRs-ROS crosstalk in plant development. Full article