Antioxidants, Volume 12, Issue 11 (November 2023) – 118 articles

Natural flavonoids are renowned for their exceptional antioxidant properties, but their limited water solubility hampers their bioavailability. One approach to enhancing their water solubility and antioxidant activity involves the use of cyclodextrin (CD) inclusion. This study investigated the impact of CD inclusion on the three primary radical scavenging mechanisms associated with flavonoid antioxidant activity, utilizing apigenin as a representative flavonoid and employing density functional theory (DFT) calculations. Initially, the optimized geometries of CD−apigenin inclusion complexes were analyzed, revealing the formation of hydrogen bonds between CD and apigenin. In less polar environments, the inclusion complex strengthened the bond dissociation enthalpies of hydroxyl groups, thereby reducing antioxidant activity. Conversely, in polar environments, the inclusion complex had the opposite effect by lowering proton affinity. These findings align with experimental results demonstrating that CD inclusion complexation enhances flavonoid antioxidant activity in aqueous ethanol solutions. Full article

The article presents a review of the relationships between melatonin and neurodevelopmental disorders. First, the antioxidant properties of melatonin and its physiological effects are considered to understand better the role of melatonin in typical and atypical neurodevelopment. Then, several neurodevelopmental disorders occurring during infancy, such as autism spectrum disorder or neurogenetic disorders associated with autism (including Smith–Magenis syndrome, Angelman syndrome, Rett’s syndrome, Tuberous sclerosis, or Williams–Beuren syndrome) and neurodevelopmental disorders occurring later in adulthood like bipolar disorder and schizophrenia, are discussed with regard to impaired melatonin production and circadian rhythms, in particular, sleep–wake rhythms. This article addresses the issue of overlapping symptoms that are commonly observed within these different mental conditions and debates the role of abnormal melatonin production and altered circadian rhythms in the pathophysiology and behavioral expression of these neurodevelopmental disorders. Full article

Acute respiratory distress syndrome (ARDS) is a life-threatening pulmonary condition characterized by the sudden onset of respiratory failure, pulmonary edema, dysfunction of endothelial and epithelial barriers, and the activation of inflammatory cascades. Despite the increasing number of deaths attributed to ARDS, a comprehensive therapeutic approach for managing patients with ARDS remains elusive. To elucidate the pathological mechanisms underlying ARDS, numerous studies have employed various preclinical models, often utilizing lipopolysaccharide as the ARDS inducer. Accumulating evidence emphasizes the pivotal role of reactive oxygen species (ROS) in the pathophysiology of ARDS. Both preclinical and clinical investigations have asserted the potential of antioxidants in ameliorating ARDS. This review focuses on various sources of ROS, including NADPH oxidase, uncoupled endothelial nitric oxide synthase, cytochrome P450, and xanthine oxidase, and provides a comprehensive overview of their roles in ARDS. Additionally, we discuss the potential of using antioxidants as a strategy for treating ARDS. Full article

Ginger is an herbaceous and flowering plant renowned for its rhizome, which is widely employed as both a spice and an herb. Since ancient times, ginger has been consumed in folk medicine and traditional cuisines for its favorable health effects. Different in vitro and in vivo studies have disclosed the advantageous physiological aspects of ginger, primarily due to its antioxidant, anti-inflammatory, antimicrobial, and anti-carcinogenic properties. These health-promoting features are linked to the variety of bioactive compounds that are present in ginger. Following the advancement in consumer awareness and the industrial demand for organic antioxidants and functional ingredients, the application of ginger and its derivatives has been broadly investigated in a wide range of food products. The prominent features transmitted by ginger into different food areas are antioxidant and nutraceutical values (bakery); flavor, acceptability, and techno-functional characteristics (dairy); hedonic and antimicrobial properties (beverages); oxidative stability, tenderization, and sensorial attributes (meat); and shelf life and sensorial properties (film, coating, and packaging). This review is focused on providing a comprehensive overview of the tendencies in the application of ginger and its derivatives in the food industry and concurrently briefly discusses the beneficial aspects and processing of ginger. Full article

Plants are exposed to a variety of abiotic and biotic stresses leading to increased formation of reactive oxygen species (ROS) in plant cells. ROS are capable of oxidizing proteins, pigments, lipids, nucleic acids, and other cell molecules, disrupting their functional activity. During the process of evolution, numerous antioxidant systems were formed in plants, including antioxidant enzymes and low molecular weight non-enzymatic antioxidants. Antioxidant systems perform neutralization of ROS and therefore prevent oxidative damage of cell components. In the present review, we focus on the biosynthesis of non-enzymatic antioxidants in higher plants cells such as ascorbic acid (vitamin C), glutathione, flavonoids, isoprenoids, carotenoids, tocopherol (vitamin E), ubiquinone, and plastoquinone. Their functioning and their reactivity with respect to individual ROS will be described. This review is also devoted to the modern genetic engineering methods, which are widely used to change the quantitative and qualitative content of the non-enzymatic antioxidants in cultivated plants. These methods allow various plant lines with given properties to be obtained in a rather short time. The most successful approaches for plant transgenesis and plant genome editing for the enhancement of biosynthesis and the content of these antioxidants are discussed. Full article

Spinach methanolic extract (SME) has a hepatoprotective effect due to its polyphenolic antioxidants; however, its action in parenchymal (PQ) and non-parenchymal (nPQ) cells remains unknown. This study investigates the hepatoprotective effect of SME on streptozotocin-induced hyperglycemic rats (STZ), focusing on immunohistochemical analyses. Methods: The extract was prepared, and the total polyphenols and antioxidant activity were quantified. Adult male Wistar rats were divided into four groups (n = 8): normoglycemic rats (NG), STZ-induced hyperglycemic (STZ), STZ treated with 400 mg/kg SME (STZ-SME), and NG treated with SME (SME) for 12 weeks. Serum liver transaminases and lipid peroxidation levels in tissue were determined. The distribution pattern and relative levels of markers related to oxidative stress [reactive oxygen species (ROS), superoxide dismutase-1, catalase, and glutathione peroxidase-1], of cytoprotective molecules [nuclear NRF2 and heme oxygenase-1 (HO-1)], of inflammatory mediators [nuclear NF-κB, TNF-α], proliferation (PCNA), and of fibrogenesis markers [TGF-β, Smad2/3, MMP-9, and TIMP1] were evaluated. Results: SME had antioxidant capacity, and it lowered serum transaminase levels in STZ-SME compared to STZ. It reduced NOX4 staining, and lipid peroxidation levels were related to low formation of ROS. In STZ-SME, the immunostaining for antioxidant enzymes increased in nPQ cells compared to STZ. However, enzymes were also localized in extra and intracellular vesicles in STZ. Nuclear NRF2 staining and HO-1 expression in PQ and nPQ were higher in STZ-SME than in STZ. Inflammatory factors were decreased in STZ-SME and were related to the percentage decrease in NF-κB nuclear staining in nPQ cells. Similarly, TGF-β (in the sinusoids) and MMP-9 (in nPQ) were increased in the STZ-SME group compared to the other groups; however, staining for CTGF, TIMP1, and Smad2/3 was lower. Conclusions: SME treatment in hyperglycemic rats induced by STZ may have hepatoprotective properties due to its scavenger capacity and the regulation of differential expression of antioxidant enzymes between the PQ and nPQ cells, reducing inflammatory and fibrogenic biomarkers in liver tissue. Full article

Cancer metabolic reprogramming is a complex process that provides malignant cells with selective advantages to grow and propagate in the hostile environment created by the immune surveillance of the human organism. This process underpins cancer proliferation, invasion, antioxidant defense, and resistance to anticancer immunity and therapeutics. Perhaps not surprisingly, metabolic rewiring is considered to be one of the “Hallmarks of cancer”. Notably, this process often comprises various complementary and overlapping pathways. Today, it is well known that highly selective inhibition of only one of the pathways in a tumor cell often leads to a limited response and, subsequently, to the emergence of resistance. Therefore, to increase the overall effectiveness of antitumor drugs, it is advisable to use multitarget agents that can simultaneously suppress several key processes in the tumor cell. This review is focused on a group of plant-derived natural compounds that simultaneously target different pathways of cancer-associated metabolism, including aerobic glycolysis, respiration, glutaminolysis, one-carbon metabolism, de novo lipogenesis, and β-oxidation of fatty acids. We discuss only those compounds that display inhibitory activity against several metabolic pathways as well as a number of important signaling pathways in cancer. Information about their pharmacokinetics in animals and humans is also presented. Taken together, a number of known plant-derived compounds may target multiple metabolic and signaling pathways in various malignancies, something that bears great potential for the further improvement of antineoplastic therapy. Full article

The imbalance of redox homeostasis contributes to neurodegeneration, including that related to the visual system. Mitochondria, essential in providing energy and responsible for several cell functions, are a significant source of reactive oxygen and/or nitrogen species, and they are, in turn, sensitive to free radical imbalance. Dysfunctional mitochondria are implicated in the development and progression of retinal pathologies and are directly involved in retinal neuronal degeneration. Retinal ganglion cells (RGCs) are higher energy consumers susceptible to mitochondrial dysfunctions that ultimately cause RGC loss. Proper redox balance and mitochondrial homeostasis are essential for maintaining healthy retinal conditions and inducing neuroprotection. In this respect, the antioxidant treatment approach is effective against neuronal oxidative damage and represents a challenge for retinal diseases. Here, we highlighted the latest findings about mitochondrial dysfunction in retinal pathologies linked to RGC degeneration and discussed redox-related strategies with potential neuroprotective properties. Full article

In recent years, there has been a focus on breeding wheat with high anthocyanin levels in order to improve food quality and human health. The objective of this study was to examine the antioxidant and geroprotective properties of wheat bran extracts using both in vitro and in vivo research methods. Two wheat lines were used: one with uncolored pericarp (anthocyanin-free) and another with colored pericarp (anthocyanin-containing). These lines differed in a specific region of chromosome 2A containing the Pp3/TaMyc1 gene, which regulates anthocyanin production. High-performance liquid chromatography-mass spectrometry revealed the presence of cyanidin glucoside and cyanidin arabinoside in the anthocyanin-containing wheat bran extract (+AWBE), while no anthocyanins were found in the anthocyanin-free wheat bran extract (−AWBE). The +AWBE showed higher radical scavenging activity (DPPH and ABTS assays) and membrane protective activity (AAPH oxidative hemolysis model) compared to the −AWBE. Both extracts extended the lifespan of female Drosophila, indicating geroprotective properties. This study demonstrates that wheat bran extracts with high anthocyanin levels have antioxidant and geroprotective effects. However, other secondary metabolites in wheat bran can also contribute to its antioxidant and geroprotective potential. Full article

COVID-19, caused by the SARS-CoV-2 coronavirus, emerged as a global pandemic in late 2019, resulting in significant global public health challenges. The emerging evidence suggests that diminished high-density lipoprotein (HDL) cholesterol levels are associated with the severity of COVID-19, beyond inflammation and oxidative stress. Here, we used nuclear magnetic resonance spectroscopy to compare the lipoprotein and metabolic profiles of COVID-19-infected patients with non-COVID-19 pneumonia. We compared the control group and the COVID-19 group using inflammatory markers to ensure that the differences in lipoprotein levels were due to COVID-19 infection. Our analyses revealed supramolecular phospholipid composite (SPC), phenylalanine, and HDL-related parameters as key discriminators between COVID-19-positive and non-COVID-19 pneumonia patients. More specifically, the levels of HDL parameters, including apolipoprotein A-I (ApoA-I), ApoA-II, HDL cholesterol, and HDL phospholipids, were significantly different. These findings underscore the potential impact of HDL-related factors in patients with COVID-19. Significantly, among the HDL-related metrics, the cholesterol efflux capacity (CEC) displayed the strongest negative association with COVID-19 mortality. CEC is a measure of how well HDL removes cholesterol from cells, which may affect the way SARS-CoV-2 enters cells. In summary, this study validates previously established markers of COVID-19 infection and further highlights the potential significance of HDL functionality in the context of COVID-19 mortality. Full article

Amyotrophic lateral sclerosis (ALS) is considered a fatal progressive degeneration of motor neurons (MN) caused by oxidative stress and mitochondrial dysfunction. There are currently no treatments available. The most common inherited form of ALS is the C9orf72 mutation (C9-ALS). The proline–arginine dipeptide repeat protein (PR-DPR) produced by C9-ALS has been confirmed to be a functionally acquired pathogenic factor that can cause increased ROS, mitochondrial defects, and apoptosis in motor neurons. Pectolinarigenin (PLG) from the traditional medicinal herb Linaria vulgaris has antioxidant and anti-apoptotic properties. I established a mouse NSC-34 motor neuron cell line model expressing PR-DPR and confirmed the neuroprotective effect of PLG. The results showed that ROS production and apoptosis caused by PR-DPR could be improved by PLG treatment. In terms of mechanism research, PR-DPR inhibited the activity of the mitochondrial fusion proteins OPA1 and mitofusin 2. Conversely, the expression of fission protein fission 1 and dynamin-related protein 1 (DRP1) increased. However, PLG treatment reversed these effects. Furthermore, I found that PLG increased the expression and deacetylation of OPA1. Deacetylation of OPA1 enhances mitochondrial fusion and resistance to apoptosis. Finally, transfection with Sirt3 small interfering RNA abolished the neuroprotective effects of PLG. In summary, the mechanism by which PLG alleviates PR-DPR toxicity is mainly achieved by activating the SIRT3/OPA1 axis to regulate the balance of mitochondrial dynamics. Taken together, the potential of PLG in preclinical studies for C9-ALS drug development deserves further evaluation. Full article

The endoplasmic reticulum is a subcellular organelle key in the control of synthesis, folding, and sorting of proteins. Under endoplasmic reticulum stress, an adaptative unfolded protein response is activated; however, if this activation is prolonged, cells can undergo cell death, in part due to oxidative stress and mitochondrial fragmentation. Here, we report that endoplasmic reticulum stress activates c-Abl tyrosine kinase, inducing its translocation to mitochondria. We found that endoplasmic reticulum stress-activated c-Abl interacts with and phosphorylates the mitochondrial fusion protein MFN2, resulting in mitochondrial fragmentation and apoptosis. Moreover, the pharmacological or genetic inhibition of c-Abl prevents MFN2 phosphorylation, mitochondrial fragmentation, and apoptosis in cells under endoplasmic reticulum stress. Finally, in the amyotrophic lateral sclerosis mouse model, where endoplasmic reticulum and oxidative stress has been linked to neuronal cell death, we demonstrated that the administration of c-Abl inhibitor neurotinib delays the onset of symptoms. Our results uncovered a function of c-Abl in the crosstalk between endoplasmic reticulum stress and mitochondrial dynamics via MFN2 phosphorylation. Full article

To date, Alzheimer’s disease (AD) has grown to be a predominant health challenge that disturbs the elderly population. Studies have shown that mitochondrial dysfunction is one of the most significant features of AD. Transplantation therapy of healthy mitochondria (mitotherapy), as a novel therapeutic strategy to restore mitochondrial function, is proposed to treat the mitochondria−associated disease. Also, the molecular mechanism of mitotherapy remains unclear. Here, we applied the mitotherapy in AD model mice induced by amyloid−β (Aβ) plaque deposition and suggested that autophagy would be an important mechanism of the mitotherapy. After the healthy mitochondria entered the defective neuronal cells damaged by the misfolded Aβ protein, autophagy was activated through the NAD⁺−dependent deacetylase sirtuin 1 (SIRT1) signal. The damaged mitochondria and Aβ protein were eliminated by autophagy, which could also decrease the content of radical oxygen species (ROS). Moreover, the levels of brain−derived neurotrophic factor (BDNF) and extracellular−regulated protein kinases (ERK) phosphorylation increased after mitotherapy, which would be beneficial to repair neuronal function. As a result, the cognitive ability of AD animals was ameliorated in a water maze test after the healthy mitochondria were administrated to the mice. The study indicated that mitotherapy would be an effective approach to AD treatment through the mechanism of autophagy activation. Full article

The intracellular redox-active labile iron pool (LIP) is weakly chelated and available for integration into the iron metalloproteins that are involved in diverse cellular processes, including cancer cell-specific metabolic oxidative stress. Abnormal iron metabolism and elevated LIP levels are linked to the poor survival of lung cancer patients, yet the underlying mechanisms remain unclear. Depletion of the LIP in non-small-cell lung cancer cell lines using the doxycycline-inducible overexpression of the ferritin heavy chain (Ft-H) (H1299 and H292), or treatment with deferoxamine (DFO) (H1299 and A549), inhibited cell growth and decreased clonogenic survival. The Ft-H overexpression-induced inhibition of H1299 and H292 cell growth was also accompanied by a significant delay in transit through the S-phase. In addition, both Ft-H overexpression and DFO in H1299 resulted in increased single- and double-strand DNA breaks, supporting the involvement of replication stress in the response to LIP depletion. The Ft-H and DFO treatment also sensitized H1299 to VE-821, an inhibitor of ataxia telangiectasis and Rad2-related (ATR) kinase, highlighting the potential of LIP depletion, combined with DNA damage response modifiers, to alter lung cancer cell responses. In contrast, only DFO treatment effectively reduced the LIP, clonogenic survival, cell growth, and sensitivity to VE-821 in A549 non-small-cell lung cancer cells. Importantly, the Ft-H and DFO sensitized both H1299 and A549 to chemoradiation in vitro, and Ft-H overexpression increased the efficacy of chemoradiation in vivo in H1299. These results support the hypothesis that the depletion of the LIP can induce genomic instability, cell death, and potentiate therapeutic responses to chemoradiation in NSCLC. Full article

Biological aging is a relevant risk factor for chronic diseases, and several indicators for measuring this factor have been proposed, with telomere length (TL) among the most studied. Oxidative stress may regulate telomere shortening, which is implicated in the increased risk. Using a novel estimator for TL, we examined whether adherence to the Mediterranean diet (MedDiet), a highly antioxidant-rich dietary pattern, is associated with longer TL. We determined TL using DNA methylation algorithms (DNAmTL) in 414 subjects at high cardiovascular risk from Spain. Adherence to the MedDiet was assessed by a validated score, and genetic variants in candidate genes and at the genome-wide level were analyzed. We observed several significant associations (p < 0.05) between DNAmTL and candidate genes (TERT, TERF2, RTEL1, and DCAF4), contributing to the validity of DNAmTL as a biomarker in this population. Higher adherence to the MedDiet was associated with lower odds of having a shorter TL in the whole sample (OR = 0.93; 95% CI: 0.85–0.99; p = 0.049 after fully multivariate adjustment). Nevertheless, this association was stronger in women than in men. Likewise, in women, we observed a direct association between adherence to the MedDiet score and DNAmTL as a continuous variable (beta = 0.015; SE: 0.005; p = 0.003), indicating that a one-point increase in adherence was related to an average increase of 0.015 ± 0.005 kb in TL. Upon examination of specific dietary items within the global score, we found that fruits, fish, “sofrito”, and whole grains exhibited the strongest associations in women. The novel score combining these items was significantly associated in the whole population. In the genome-wide association study (GWAS), we identified ten polymorphisms at the suggestive level of significance (p < 1 × 10⁻⁵) for DNAmTL (intergenics, in the IQSEC1, NCAPG2, and ABI3BP genes) and detected some gene–MedDiet modulations on DNAmTL. As this is the first study analyzing the DNAmTL estimator, genetics, and modulation by the MedDiet, more studies are needed to confirm these findings. Full article

Several plants of the genus Tragia L. have shown antibacterial, fungicidal, and antiproliferative activity, among other types of activities; however, most species of the genus have not been investigated. Tragia volubilis L. is native to tropical America and Africa, and although it has been reported as medicinal in the literature, it has not been thoroughly investigated. In this study, the phytochemical screening, isolation, and identification of compounds and the determination of the antioxidant activity of the aqueous extract of Tragia volubilis L. and its partitions were carried out. Ethyl acetate and n-butanol partitions of the extract present high antioxidant activity according to the Antioxidant Activity Index. Due to their activity, these partitions were tested on RKO cells as a representative model, both individually and in combination with Doxorubicin. It was found that the partitions significantly reduced the effect of Doxorubicin, as well as the expression of proteins involved in DNA damage and cell death. While the reduction of the chemotherapeutic effect of Doxorubicin on tumor cells may not be a desired outcome in therapeutic settings, the findings of the study are valuable in revealing the antioxidant potential of Tragia volubilis L. and its partitions. This highlights the importance of carefully regulating the application of antioxidants, especially in the context of cancer chemotherapy. Full article

The efficiency of HT and that of some of its hydrophobic derivatives and their distribution and effective concentrations were investigated in fish oil-in-water nanoemulsions. For this purpose, we carried out two sets of independent, but complementary, kinetic experiments in the same intact fish nanoemulsions. In one of them, we monitored the progress of lipid oxidation in intact nanoemulsions by monitoring the formation of conjugated dienes with time. In the second set of experiments, we determined the distributions and effective concentrations of HT and its derivatives in the same intact nanoemulsions as those employed in the oxidation experiments. Results show that the antioxidant efficiency is consistent with the “cut-off” effect—the efficiency of HT derivatives increases upon increasing their hydrophobicity up to the octyl derivative after which a further increase in the hydrophobicity decreases their efficiency. Results indicate that the effective interfacial concentration is the main factor controlling the efficiency of the antioxidants and that such efficiency strongly depends on the surfactant concentration and on the oil-to-water (o/w) ratio employed to prepare the nanoemulsions. Full article

Azadirachtin (AZD), a limonoid from the versatile, tropical neem tree (Azadirachta indica), is well known for its many medicinal, and pharmacological effects. Its effects as an anti-oxidant, anti-inflammatory, and anti-cancer agent are well known. However, not many studies have explored the effects of AZD on toxicities induced by benzo(a)pyrene (B(a)P), a toxic component of cigarette smoke known to cause DNA damage and cell cycle arrest, leading to different kinds of cancer. In the present study, using HepG2 cells, we investigated the protective effects of Azadirachtin (AZD) against B(a)P-induced oxidative/nitrosative and metabolic stress and mitochondrial dysfunction. Treatment with 25 µM B(a)P for 24 h demonstrated an increased production of reactive oxygen species (ROS), followed by increased lipid peroxidation and DNA damage presumably, due to the increased metabolic activation of B(a)P by CYP 450 1A1/1A2 enzymes. We also observed intrinsic and extrinsic apoptosis, alterations in glutathione-dependent redox homeostasis, cell cycle arrest, and inflammation after B(a)P treatment. Cells treated with 25 µM AZD for 24 h showed decreased oxidative stress and apoptosis, partial protection from DNA damage, and an improvement in mitochondrial functions and bioenergetics. The improvement in antioxidant status, anti-inflammatory potential, and alterations in cell cycle regulatory markers qualify AZD as a potential therapeutic in combination with anti-cancer drugs. Full article

Exposure to phoxim at low levels caused bioaccumulation with neurotoxicity but also induced oxidative stress, tissue damage, and abnormal nutrient metabolism. This study described that vitamin E ameliorates phoxim-induced nephrotoxicity via inhibiting mitochondrial apoptosis. In vivo, 24 healthy piglets were treated with phoxim (0 mg/kg and 500 mg/kg) and vitamin E + phoxim (vitamin E + phoxim: 200 mg/kg + 500 mg/kg). In vitro, PK15 cells were treated with phoxim (0 mg/L and 1 mg/L) and vitamin E + phoxim (phoxim + vitamin E: 1 mg/L + 1 mg/L) for 12 h and 24 h. Our results indicated that accumulation of ROS, oxidative stress, and renal cell injury through stimulation of mitochondrial apoptosis resulted in phoxim-induced nephrotoxicity. Phoxim resulted in swollen mitochondria, blurred internal cristae, renal glomerular atrophy, and renal interstitial fibrosis. Vitamin E alleviated the adverse effects of phoxim by reducing ROS and improving antioxidant capacity in vivo and in vitro. Vitamin E significantly increased SDH in vitro (p < 0.01), while it decreased ROS, Bad, and cyto-c in vitro and SOD and CAT in vivo (p < 0.05). Vitamin E ameliorated phoxim-induced renal histopathologic changes, and mitochondria swelled. In addition, vitamin E regulates phoxim-induced apoptosis by alleviating oxidative damage to the mitochondria. Full article

This study aims to investigate the neuroprotective effects of nootkatone (NKT), a sesquiterpenoid compound isolated from grapefruit, in an MPTP-induced Parkinson’s disease (PD) mouse model. NKT restored MPTP-induced motor impairment and dopaminergic neuronal loss and increased the expression of neurotrophic factors like BDNF, GDNF, and PGC-1α. In addition, NKT inhibited microglial and astrocyte activation and the expression of pro-inflammatory markers like iNOS, TNF-α, and IL-1β and oxidative stress markers like 4-HNE and 8-OHdG. NKT increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2)-driven antioxidant enzymes like HO-1 and NQO-1 in astrocytes, but not in neurons or microglia in MPTP-treated mice. To investigate whether Nrf2 mediates the anti-inflammatory, antioxidant, or neuroprotective effects of NKT, mice were pretreated with Nrf2-specific inhibitor brusatol (BT) prior to NKT treatment. BT attenuated the NKT-mediated inhibition of 4-HNE and 8-OHdG and the number of Nrf2⁺/HO-1⁺/NQO1⁺ cells co-localized with GFAP⁺ astrocytes in the substantia nigra of MPTP-treated mice. In addition, BT reversed the effects of NKT on dopaminergic neuronal cell death, neurotrophic factors, and pro-/anti-inflammatory cytokines in MPTP-treated mice. Collectively, these data suggest that astrocytic Nrf2 and its downstream antioxidant molecules play pivotal roles in mediating the neuroprotective and anti-inflammatory effects of NKT in an MPTP-induced PD mouse model. Full article

Phytoseiid mite Neoseiulus barkeri is a crucial biological control agent utilized to control pest mites and many insects in crops all over the world. However, they are vulnerable to multiple environmental pressures, with high-temperature stress being the most significant challenge. Heat stress disrupts the balance of reactive oxygen species (ROS) levels in organisms, resulting in oxidative stress within the body. Antioxidant enzymes play a crucial role in effectively neutralizing and clearing ROS. In this study, comparative transcriptomics and quantitative real-time PCR (qRT-PCR) were employed to assess the impact of short-term heat stress on the transcript expression of antioxidant enzyme genes in N. barkeri. We primarily identified four antioxidant enzyme genes (NbSOD, NbPrx, NbCAT, and NbGPX) in N. barkeri after exposure to short-term heat stress. Then, new data on the expression patterns of these genes were generated. RNA sequencing and bioinformatics analysis revealed that NbSOD belongs to the Fe/Mn family of superoxide dismutase (SOD), which was identified as MnSOD. NbPrx was classified as a 1-Cys peroxiredoxin of the peroxidase family, whereas NbCAT was recognized as a classical catalase, and NbGPX was determined as cytoplasmic glutathione peroxidase-1 (GPX1). Transcriptional expression analysis of these four genes was conducted at different high temperatures: 36 °C, 38 °C, and 40 °C for 2, 4, and 6 h. The results also showed that all four genes exhibited significant up-regulation in response to short-term heat stress. Similarly, the highest expression levels for NbSOD, NbPrx, and NbCAT were observed at 40 °C for 4 h. However, NbGPX displayed its maximum expression value at 38 °C for 4 h. Overall, the obtained data suggest that short-term heat stress increases levels of ROS generated inside living organisms, which disrupts the oxidative balance and leads to alterations in the expression levels of antioxidant enzyme genes. Full article

Iron plays an essential role in various physiological processes. A disruption in iron homeostasis can lead to severe consequences, including impaired neurodevelopment, neurodegenerative disorders, stroke, and cancer. Interestingly, the link between mental health disorders and iron homeostasis has not received significant attention. Therefore, our understanding of iron metabolism in the context of psychological diseases is incomplete. In this review, we aim to discuss the pathologies and potential mechanisms that relate to iron homeostasis in associated mental disorders. We propose the hypothesis that maintaining brain iron homeostasis can support neuronal physiological functions by impacting key enzymatic activities during neurotransmission, redox balance, and myelination. In conclusion, our review highlights the importance of investigating the relationship between trace element nutrition and the pathological process of mental disorders, focusing on iron. This nutritional perspective can offer valuable insights for the clinical treatment of mental disorders. Full article

The antioxidant effect of cuttlefish (Sepia officinalis) ink (CFI) was analysed in the present study. A model system consisting of minced seabream (Sparus aurata) muscle and different concentrations of an aqueous extract of CFI was subjected to a heat (50 °C) treatment for 12 days. The effects of the CFI content and the heating time on lipid oxidation (conjugated diene (CD), conjugated triene (CT), and peroxide values and fluorescent compound formation), hydrolysis (free fatty acid content) development, and changes in the fatty acid (FA) profile (polyene index (PI), unsaturated FA content, ω3/ω6 ratio) were determined. The addition of the aqueous extract of CFI led to a lower (p < 0.05) development of lipid oxidation (CD, CT, and fluorescent compound determination) and to a higher (p < 0.05) retention of unsaturated FAs (PI determination). More important effects were found with increased CFI concentrations and at advanced heating times. However, a definite effect on lipid hydrolysis development (FFA value) could not be inferred. A new approach for the beneficial use of cuttlefish ink is presented. According to the direct relationship between rancidity stability and nutritional and sensory values, the present study provides a new strategy for the quality enhancement of thermally treated seafood. Full article

The traditional processing of Dendrobium officinale (DO) is performed in five necessary processing steps: processing fresh strips, drying at 85 °C, curling, molding, and drying at 35 °C (Fengdou). The antioxidant activity of DO is increased after it is processed into Fengdou. To comprehensively analyze the changes in the functional components, a plant-wide target metabolomics approach was employed. In total, 739 differential chemical components were identified in five processing treatments, mainly highlighting differences in the levels of phenolic acids, flavonoids, lipids, and amino acids and their derivatives, and the glycosylation of aglycone resulted in the upregulation of flavonoid glycoside levels. Temperature is a key factor in DO processing during production. In addition, the enrichment of specific differential chemical components was found mainly in five different metabolic pathways: glucosinolate biosynthesis, linoleic acid metabolism, flavonoid biosynthesis, phenylpropanoid biosynthesis, and ubiquinone and other terpene quinone biosynthesis. A correlation analysis clarified that total phenols and flavonoids show a significant positive correlation with antioxidant capacity. This study provides new insights into the influence of the processing processes on DO quality, which may provide guidance for the high-quality production of DO. Full article

Age-related hearing loss (ARHL) impairs the quality of life in elderly persons. ARHL is associated with comorbidities, such as depression, falls, or frailty. Frailty syndrome is related to poor health outcomes in old age. ARHL is a potentially modifiable risk factor for frailty. Oxidative stress has been proposed as a key factor underlying the onset and/or development of ARHL and frailty. Cocoa has high levels of polyphenols and provides many health benefits due to its antioxidant properties. Male and female C57Bl/6J mice were randomly assigned to two study groups: animals receiving a cocoa-supplemented diet and the other receiving a standard diet. Then, at the ages of 6, 14, and 22 months, hearing and frailty were measured in all mice. Auditory steady-state responses (ASSR) threshold shifts were measured to different frequencies. The frailty score was based on the “Valencia Score” adapted to the experimental animals. The total antioxidant capacity and total polyphenols in urine samples were also measured. Significant improvements in hearing ability are observed in the cocoa groups at 6, 14, and 22 months compared to the no cocoa group. The cocoa diet significantly retards the development of frailty in mice. Cocoa increases the concentration of polyphenols excreted in the urine, which increases the total antioxidant capacity. In conclusion, cocoa, due to its antioxidant properties, leads to significant protection against ARHL and frailty. Full article

It has been proposed that lipid oxidation reactions in edible oils primarily occur in reverse micelles (RM) of amphiphilic components. While the prooxidative effect of RM has been demonstrated, the mechanism involved is not fully understood. Both reductions and enhancements in the antioxidant efficacy (AE) of α-tocopherol and Trolox have been observed in different studies when phosphatidylcholine (PC) was added and PC RM were formed. However, most of these investigations employed lipid systems consisting of stripped vegetable oil diluted in saturated medium-chain triacylglycerols (MCT) and utilized antioxidant concentrations well below those found in edible oils. These two specific factors were investigated in the present study. The effect of RM of purified egg yolk PC on the AE of 1.16 mmol kg⁻¹ α-tocopherol or Trolox in stripped sunflower oil (SSO) was studied by the Rancimat (100 °C) and oven (50 °C) tests. Increasing PC concentrations (50–1000 ppm) had no significant impact on α-tocopherol, but substantial reductions in AE were observed for Trolox. This phenomenon may be attributed to the partitioning of Trolox into the pre-existing PC micelles, suggesting that primary oxidation reactions occurred in the continuous lipid phase. In addition, the effectiveness of both antioxidants decreased significantly in the presence of PC when a low antioxidant concentration (0.06 mmol kg⁻¹) was assayed in SSO:MCT (1:3, w/w). Full article

(1) Background: The involvement of redox balance alterations and innate immunity is suggested to play a key role in the pathogenesis of sarcopenia. This investigation aimed to define and relate modifications in circulating markers of redox homeostasis and the innate immune response in human sarcopenia. (2) Methods: A total of 32 subjects aged >65 years old and affected by sarcopenia according to the second “European Working Group on sarcopenia in older people” guidelines were compared with 40 non-sarcopenic age-matched controls. To assess systemic redox homeostasis, reduced (GSH) and oxidized (GSSG) blood glutathione and plasma malondialdehyde (MDA)– and 4-hydroxy-2,3-nonenal (HNE)–protein adducts were measured. Immune cells and circulating interleukins were determined to compare the innate immune response between both groups. (3) Results: Impaired redox balance in sarcopenic patients, characterized by a high blood GSSG/GSH ratio and plasma MDA/HNE–protein adducts, was sustained by reduced antioxidants in peripheral blood mononuclear cells. Furthermore, sarcopenic patients showed higher neutrophil-to-lymphocyte ratios and interleukin (IL)-4, IL-6, IL-10, and tumor necrosis factor (TNF) with respect to non-sarcopenic patients. Linear regression analysis resulted in a strong association between redox balance and immune response markers in the sarcopenic group. (4) Conclusions: These results support the interplay between redox homeostasis alteration and disruption of the innate immune response in the pathogenesis of sarcopenia. Full article

The cerebellum is responsible for complex motor functions, like maintaining balance and stance, coordination of voluntary movements, motor learning, and cognitive tasks. During aging, most of these functions deteriorate, which results in falls and accidents. The aim of this work was to elucidate the effect of a standardized pomegranate extract during four months of supplementation in elderly mice to prevent frailty and improve the oxidative state. Male C57Bl/6J eighteen-month-old mice were evaluated for frailty using the “Valencia Score” at pre-supplementation and post-supplementation periods. We analyzed lipid peroxidation in the cerebellum and brain cortex and the glutathione redox status in peripheral blood. In addition, a set of aging-related genes in cerebellum and apoptosis biomarkers was measured via real-time polymerase chain reaction (RT-PCR). Our results showed that pomegranate extract supplementation improved the motor skills of C57Bl/6J aged mice in motor coordination, neuromuscular function, and monthly weight loss, but no changes in grip strength and endurance were found. Furthermore, pomegranate extract reversed the increase in malondialdehyde due to aging in the cerebellum and increased the reduced glutathione/oxidized glutathione (GSH/GSSG) ratio in the blood. Finally, aging and apoptosis biomarkers improved in aged mice supplemented with pomegranate extract in the cerebellum but not in the cerebral cortex. Full article

The genus Salvia L., belonging to the Lamiaceae family, contains more than 900 species distributed in various parts of the world. It is a genus containing aromatic plants used both in the culinary field and above all in the cosmetic area to produce several perfumes. Salvia fruticosa Mill., notoriously known as Greek Salvia, is a plant used since ancient times in traditional medicine, but today cultivated and used in various parts of Europe and Africa. Polar and apolar extracts of this plant confirmed the presence of several metabolites such as abietane and labdane diterpenoids, triterpenoids, steroids, and some flavonoids, causing interesting properties such as sedative, carminative, and antiseptic, while its essential oils (EOs) are mainly characterized by compounds such as 1,8-cineole and camphor. The aim of this work concerns the chemical analysis by GC and GC-MS, and the investigation of the biological properties, of the EO of S. fruticosa plants collected in eastern Sicily. The gas-chromatographic analysis confirmed the presence of 1,8-cineole (17.38%) and camphor (12.81%), but at the same time, also moderate amounts of α-terpineol (6.74%), β-myrcene (9.07%), camphene (8.66%), β-pinene (6.55%), and α-pinene (6.45%). To study the protective effect of EOs from S. fruticosa (both the total mixture and the individual compounds) on possible damage induced by heavy metals, an in vitro system was used in which a model organism, the liverwort Conocephalum conicum, was subjected to the effect of a mix of heavy metals (HM) prepared using values of concentrations actually measured in one of the most polluted watercourses of the Campania region, the Regi Lagni. Finally, the antioxidant response and the photosynthetic damage were examined. The exogenous application of the EO yields a resumption of the oxidative stress induced by HM, as demonstrated by the reduction in the Reactive Oxygen Species (ROS) content and by the increased activity of antioxidant enzyme catalase (CAT) and glutathione-S-transferase (GST). Furthermore, plants treated with HMs and EO showed a higher F_v/F_m (maximal quantum efficiency of PSII in the dark) with respect to HMs-only treated ones. These results clearly indicate the protective capacity of the EO of S. fruticosa against oxidative stress, which is achieved at least in part by modulating the redox state through the antioxidant pathway and on photosynthetic damage. Full article

Heme oxygenase-1 (HO-1) is an enzyme located at the endoplasmic reticulum, which is responsible for the degradation of cellular heme into ferrous iron, carbon monoxide and biliverdin-IXa. In addition to this main function, the enzyme is involved in many other homeostatic, toxic and cancer-related mechanisms. In this review, we first summarize the importance of HO-1 in physiology and pathophysiology with a focus on the digestive system. We then detail its structure and function, followed by a section on the regulatory mechanisms that control HO-1 expression and activity. Moreover, HO-2 as important further HO isoform is discussed, highlighting the similarities and differences with regard to HO-1. Subsequently, we describe the direct and indirect cytoprotective functions of HO-1 and its breakdown products carbon monoxide and biliverdin-IXa, but also highlight possible pro-inflammatory effects. Finally, we address the role of HO-1 in cancer with a particular focus on colorectal cancer. Here, relevant pathways and mechanisms are presented, through which HO-1 impacts tumor induction and tumor progression. These include oxidative stress and DNA damage, ferroptosis, cell cycle progression and apoptosis as well as migration, proliferation, and epithelial-mesenchymal transition. Full article