Antioxidants, Volume 13, Issue 6 (June 2024) – 102 articles

Starch is a common source of carbohydrates in aqua feed. High-starch diet can cause hepatic injury and lipid accumulation in fish. Mangiferin (MGF) can regulate lipid metabolism and protect the liver, but there is limited research on its effects in fish. In the present study, we investigated whether MGF could ameliorate high-starch-induced hepatic damage and lipid accumulation in channel catfish. The channel catfish (Ictalurus punctatus) were fed one of four experimental diets for eight weeks: a control diet (NCD), a high-starch diet (HCD), an HCD supplemented with 100 mg/kg MGF (100 MGF), and an HCD supplemented with 500 mg/kg MGF (500 MGF). The results demonstrated that the weight gain rate (WGR) (p = 0.031), specific growth rate (SGR) (p = 0.039), and feed conversion efficiency (FCE) (p = 0.040) of the 500 MGF group were significantly higher than those of the NCD group. MGF supplementation alleviated liver damage and improved antioxidant capacity (T-AOC) compared to those of the HCD group (p = 0.000). In addition, dietary MGF significantly reduced plasma glucose (GLU) (p = 0.000), triglyceride (TG) (p= 0.001), and low-density lipoprotein cholesterol (LDL) (p = 0.000) levels. It is noteworthy that MGF significantly reduced the plasma total cholesterol (TC) levels (p = 0.000) and liver TC levels (p = 0.005) of channel catfish. Dietary MGF improves cholesterol homeostasis by decreasing the expression of genes that are involved in cholesterol synthesis and transport (hmgcr, sqle, srebf2, sp1, and ldlr) and increasing the expression of genes that are involved in cholesterol catabolism (cyp7a1). Among them, the largest fold decrease in squalene epoxidase (sqle) expression levels was observed in the 100 MGF or 500 MGF groups compared with the HCD group, with a significant decrease of 3.64-fold or 2.20-fold (p = 0.008). And the 100 MGF or 500 MGF group had significantly decreased (by 1.67-fold or 1.94-fold) Sqle protein levels compared to those of the HCD group (p = 0.000). In primary channel catfish hepatocytes, MGF significantly down-regulated the expression of sqle (p = 0.030) and reduced cholesterol levels (p = 0.000). In NCTC 1469 cells, MGF significantly down-regulated the expression of sqle (p = 0.000) and reduced cholesterol levels (p = 0.024). In conclusion, MGF effectively inhibits sqle expression and reduces cholesterol accumulation. The current study shows how MGF supplementation regulates the metabolism and accumulation of cholesterol in channel catfish, providing a theoretical basis for the use of MGF as a dietary supplement in aquaculture. Full article

Djulis (Chenopodium formosanum), a traditional Taiwanese crop enriched with phenolic compounds and betalain pigments, is associated with various health benefits, including antioxidant and hepatoprotective effects. This study analysed the phytochemical content and antioxidant capacity of extracts from both the hull and kernel of Djulis. The hull extract, which contained higher levels of flavonoids and exhibited superior antioxidant activity compared to the kernel extract, was selected for further in vivo studies. These experiments showed that oral administration of the Djulis hull crude extract significantly mitigated lipopolysaccharide (LPS)-induced acute liver injury (ALI) in mice by increasing the activity of the antioxidant enzyme glutathione peroxidase (GPx), reducing plasma levels of pro-inflammatory cytokine interferon gamma (IFN-γ), and enhancing liver levels of the anti-inflammatory cytokine interleukin-4 (IL-4). Additionally, the extract demonstrated potential in inhibiting the TLR4/NF-κB pathway, a critical signalling pathway in inflammation and apoptosis, offering insights into its protective mechanisms. These findings underscore Djulis hull’s potential as a functional food ingredient for ALI prevention and propose a valuable application for agricultural by-products. Full article

Redox modifications to the plasma protein albumin have the potential to be used as biomarkers of disease progression and treatment efficacy in pathologies associated with inflammation and oxidative stress. One such pathology is Duchenne muscular dystrophy (DMD), a fatal childhood disease characterised by severe muscle wasting. We have previously shown in the mdx mouse model of DMD that plasma albumin thiol oxidation is increased; therefore, the first aim of this paper was to establish that albumin thiol oxidation in plasma reflects levels within mdx muscle tissue. We therefore developed a method to measure tissue albumin thiol oxidation. We show that albumin thiol oxidation was increased in both mdx muscle and plasma, with levels correlated with measures of dystropathology. In dystrophic muscle, albumin content was associated with areas of myonecrosis. The second aim was to test the ability of plasma thiol oxidation to track acute changes in dystropathology: we therefore subjected mdx mice to a single treadmill exercise session (known to increase myonecrosis) and took serial blood samples. This acute exercise caused a transient increase in total plasma albumin oxidation and measures of dystropathology. Together, these data support the use of plasma albumin thiol oxidation as a biomarker to track active myonecrosis in DMD. Full article

Protein persulfidation is a thiol-based oxidative posttranslational modification (oxiPTM) that involves the modification of susceptible cysteine thiol groups present in peptides and proteins through hydrogen sulfide (H₂S), thus affecting their function. Using sweet pepper (Capsicum annuum L.) fruits as a model material at different stages of ripening (immature green and ripe red), endogenous persulfidated proteins (persulfidome) were labeled using the dimedone switch method and identified using liquid chromatography and mass spectrometry analysis (LC-MS/MS). A total of 891 persulfidated proteins were found in pepper fruits, either immature green or ripe red. Among these, 370 proteins were exclusively present in green pepper, 237 proteins were exclusively present in red pepper, and 284 proteins were shared between both stages of ripening. A comparative analysis of the pepper persulfidome with that described in Arabidopsis leaves allowed the identification of 25% of common proteins. Among these proteins, glutathione reductase (GR) and leucine aminopeptidase (LAP) were selected to evaluate the effect of persulfidation using an in vitro approach. GR activity was unaffected, whereas LAP activity increased by 3-fold after persulfidation. Furthermore, this effect was reverted through treatment with dithiothreitol (DTT). To our knowledge, this is the first persulfidome described in fruits, which opens new avenues to study H₂S metabolism. Additionally, the results obtained lead us to hypothesize that LAP could be involved in glutathione (GSH) recycling in pepper fruits. Full article

This study explored, for the first time, the chemical composition and in vitro antioxidant and antibacterial activities of a caper leaf essential oil (EO) emulsion for possible food applications as a natural preservative. The EO was extracted by hydrodistillation from the leaves of Capparis spinosa growing wild in the Aeolian Archipelago (Sicily, Italy) and exhibited a pungent, sulphurous odour. The volatile fraction of the emulsion, analysed by SPME-GC-MS, consisted of over 100 compounds and was dominated by compounds with recognised antibacterial and antioxidant properties, namely dimethyl tetrasulfide (18.41%), dimethyl trisulfide (12.58%), methyl isothiocyanate (7.97%), and terpinen-4-ol (6.76%). The emulsion was effective against all bacterial strains tested (Listeria monocytogenes, Staphylococcus aureus, Escherichia coli, Salmonella enterica subsp. enterica serovar Enteritidis, Pseudomonas fluorescens), with L. monocytogenes exhibiting the lowest minimum inhibitory concentration (MIC = 0.02 mg/mL) while E. coli had the highest (MIC = 0.06 mg/mL). The emulsion had a good DPPH (2,2-diphenyl-1-picrylhydrazine) radical scavenging activity that was dose-dependent and equal to 42.98% at the 0.08 mg/mL level with an IC₅₀ value of 0.099 mg/mL. Based on the results, the caper leaf EO emulsion has the potential to be proposed as a natural alternative to chemical preservatives in the food industry. Full article

Oxidative stress can damage tissues and cells, and their resilience or susceptibility depends on the robustness of their antioxidant mechanisms. The latter include small molecules, proteins, and enzymes, which are linked together in metabolic pathways. Red blood cells are particularly susceptible to oxidative stress due to their large number of hemoglobin molecules, which can undergo auto-oxidation. This yields reactive oxygen species that participate in Fenton chemistry, ultimately damaging their membranes and cytosolic constituents. Fortunately, red blood cells contain robust antioxidant systems to enable them to circulate and perform their physiological functions, particularly delivering oxygen and removing carbon dioxide. Nonetheless, if red blood cells have insufficient antioxidant reserves (e.g., due to genetics, diet, disease, or toxin exposure), this can induce hemolysis in vivo or enhance susceptibility to a “storage lesion” in vitro, when blood donations are refrigerator-stored for transfusion purposes. Ergothioneine, a small molecule not synthesized by mammals, is obtained only through the diet. It is absorbed from the gut and enters cells using a highly specific transporter (i.e., SLC22A4). Certain cells and tissues, particularly red blood cells, contain high ergothioneine levels. Although no deficiency-related disease has been identified, evidence suggests ergothioneine may be a beneficial “nutraceutical.” Given the requirements of red blood cells to resist oxidative stress and their high ergothioneine content, this review discusses ergothioneine’s potential importance in protecting these cells and identifies knowledge gaps regarding its relevance in enhancing red blood cell circulatory, storage, and transfusion quality. Full article

Skeletal muscle contraction evokes numerous biochemical alterations that underpin exercise benefits. This present study aimed to elucidate the mechanism for electrical pulse stimulation (EPS)-induced antioxidant adaptation in C2C12 myotubes. We found that EPS significantly upregulated Nrf2 and a broad array of downstream antioxidant enzymes involved in multiple antioxidant systems. These effects were completely abolished by pretreatment with a ROS scavenger, N-acetylcysteine. MitoSOX-Red, CM-H2DCFDA, and EPR spectroscopy revealed a significantly higher ROS level in mitochondria and cytosol in EPS cells compared to non-stimulated cells. Seahorse and Oroboros revealed that EPS significantly increased the maximal mitochondrial oxygen consumption rate, along with an upregulated protein expression of mitochondrial complexes I/V, mitofusin-1, and mitochondrial fission factor. A post-stimulation time-course experiment demonstrated that upregulated NQO1 and GSTA2 last at least 24 h following the cessation of EPS, whereas elevated ROS declines immediately. These findings suggest an antioxidant preconditioning effect in the EPS cells. A cell viability study suggested that the EPS cells displayed 11- and 36-fold higher survival rates compared to the control cells in response to 2 and 4 mM H₂O₂ treatment, respectively. In summary, we found that EPS upregulated a large group of antioxidant enzymes in C2C12 myotubes via a contraction-mitochondrial-ROS-Nrf2 pathway. This antioxidant adaptation protects cells against oxidative stress-associated cytotoxicity. Full article

We used a replicative lifespan (RLS) experiment of K6001 yeast to screen for anti-aging compounds within lavender extract (Lavandula angustifolia Mill.), leading to the discovery of β-cyclocitral (CYC) as a potential anti-aging compound. Concurrently, the chronological lifespan (CLS) of YOM36 yeast and mammalian cells confirmed the anti-aging effect of CYC. This molecule extended the yeast lifespan and inhibited etoposide (ETO)-induced cell senescence. To understand the mechanism of CYC, we analyzed its effects on telomeres, oxidative stress, and autophagy. CYC administration resulted in notable increases in the telomerase content, telomere length, and the expression of the telomeric shelterin protein components telomeric-repeat binding factor 2 (TRF2) and repressor activator protein 1 (RAP1). More interestingly, CYC reversed H₂O₂-induced telomere damage and exhibited strong antioxidant capacity. Moreover, CYC improved the survival rate of BY4741 yeast under oxidative stress induced by 6.2 mM H₂O₂, increasing the antioxidant enzyme activity while reducing the reactive oxygen species (ROS), reactive nitrogen species (RNS), and malondialdehyde (MDA) levels. Additionally, CYC enhanced autophagic flux and free green fluorescent protein (GFP) expression in the YOM38-GFP-ATG8 yeast strain. However, CYC did not extend the RLS of K6001 yeast mutants, such as Δsod1, Δsod2, Δcat, Δgpx, Δatg2, and Δatg32, which lack antioxidant enzymes or autophagy-related genes. These findings reveal that CYC acts as an anti-aging agent by modifying telomeres, oxidative stress, and autophagy. It is a promising compound with potential anti-aging effects and warrants further study. Full article

Cisplatin is a widely used antineoplastic drug for treating various types of cancers. However, it can cause severe side effects, such as bilateral and irreversible hearing loss, which significantly impacts quality of life. Ferroptosis, an iron-dependent form of programmed cell death, has been implicated in the pathogenesis of cisplatin-induced ototoxicity. Here, we investigated the effects of nuciferine, a natural active ingredient isolated from lotus species, on the ferroptosis of cochlear hair cells. Firstly, our results demonstrated that nuciferine can protect hair cells against RSL3-induced and cisplatin-induced damage. Secondly, nuciferine treatment reduced ferrous iron (Fe²⁺) overload in cochlear hair cells via inhibiting NCOA4-mediated ferritinophagy. Inhibition of ferritinophagy by knocking down Ncoa4 alleviated cisplatin-induced ototoxicity. Importantly, nuciferine treatment mitigated cochlear hair cell loss and damage to ribbon synapse, and improved mouse hearing function in an acute cisplatin-induced hearing loss model. Our findings highlight the role of NCOA4-mediated ferritinophagy in the pathogenesis of cisplatin-induced ototoxicity and provide evidence for nuciferine as a promising protective agent for treating cisplatin-induced hearing loss. Full article

Melanin, the pigment responsible for human skin color, increases susceptibility to UV radiation, leading to excessive melanin production and hyperpigmentation disorders. This study investigated the ethanolic extract of Garcinia atroviridis fruits for its phenolic and flavonoid contents, antioxidant activity, and impact on melanogenesis pathways using qRT-PCR and Western blot analysis. Utilizing network pharmacology, molecular docking, and dynamics simulations, researchers explored G. atroviridis fruit extract’s active compounds, targets, and pharmacological effects on hyperpigmentation. G. atroviridis fruit extract exhibited antioxidant properties, scavenging DPPH^• and ABTS^•+ radicals radicals and chelating copper. It inhibited cellular tyrosinase activity and melanin content in stimulated B16F10 cells, downregulating TYR, TRP-1, phosphorylated CREB, CREB, and MITF proteins along with transcription levels of MITF, TYR, and TRP-2. LC-MS analysis identified thirty-three metabolites, with seventeen compounds selected for further investigation. Network pharmacology revealed 41 hyperpigmentation-associated genes and identified significant GO terms and KEGG pathways, including cancer-related pathways. Kaempferol-3-O-α-L-rhamnoside exhibited high binding affinity against MAPK3/ERK1, potentially regulating melanogenesis by inhibiting tyrosinase activity. Stable ligand–protein interactions in molecular dynamics simulations supported these findings. Overall, this study suggests that the ethanolic extract of G. atroviridis fruits possesses significant antioxidant, tyrosinase inhibitory, and anti-melanogenic properties mediated through key molecular targets and pathways. Full article

Xanthine Oxidoreductase (XOR) is a ubiquitous, essential enzyme responsible for the terminal steps of purine catabolism, ultimately producing uric acid that is eliminated by the kidneys. XOR is also a physiological source of superoxide ion, hydrogen peroxide, and nitric oxide, which can function as second messengers in the activation of various physiological pathways, as well as contribute to the development and the progression of chronic conditions including kidney diseases, which are increasing in prevalence worldwide. XOR activity can promote oxidative distress, endothelial dysfunction, and inflammation through the biological effects of reactive oxygen species; nitric oxide and uric acid are the major products of XOR activity. However, the complex relationship of these reactions in disease settings has long been debated, and the environmental influences and genetics remain largely unknown. In this review, we give an overview of the biochemistry, biology, environmental, and current clinical impact of XOR in the kidney. Finally, we highlight recent genetic studies linking XOR and risk for kidney disease, igniting enthusiasm for future biomarker development and novel therapeutic approaches targeting XOR. Full article

Jeriva (Syagrus romanzoffiana) is a fruit from palm trees of the Arecaceae family, widely distributed in tropical and subtropical areas of Latin America. It has low production costs and high productivity throughout the year; however, its consumption is very low, and the production goes almost entirely to feed animals or to waste. To improve its consumption, a good characterization of the whole fruit is necessary. The objective of this work was to evaluate the jeriva pulp, peel and seeds according to carotenoids, phenolic compounds, vitamin C, tocopherols and antioxidant potential using HPLC, microplate readers and spectrophotometric methods. Every part of the fruit exhibited antioxidant capacity in the ORAC and TEAC tests, which can be attributed to its high concentration of polyphenols. Carotenoids were more present in the pulp and peel and almost absent in the seeds. Vitamin C ranged from 12 ± 1 for the seeds up to 92 ± 3 mg/100 g for the pulp. The total phenolic content was quantified between 473 ± 39 for the seeds and 1089 ± 32 mg of gallic acid equivalents (GAEs)/100 g for the pulp. These results demonstrate that all parts of this fruit have important bioactive nutrients, with promising perspectives for further scientific approaches and for composing formulations of food products to enhance functional properties. Full article

Scutellarein is a key active constituent present in many plants, especially in Scutellaria baicalensis Georgi and Erigeron breviscapus (vant.) Hand-Mazz which possesses both anti-inflammatory and anti-oxidative activities. It also is the metabolite of scutellarin, with the ability to relieve LPS-induced acute lung injury (ALI), strongly suggesting that scutellarein could suppress respiratory inflammation. The present study aimed to investigate the effects of scutellarein on lung inflammation by using LPS-activated BEAS-2B cells (a human bronchial epithelial cell line) and LPS-induced ALI mice. The results showed that scutellarein could reduce intracellular reactive oxygen species (ROS) accumulation through inhibiting the activation of NADPH oxidases, markedly downregulating the transcription and translation of pro-inflammatory cytokines, including interleukin-6 (IL-6), C-C motif chemokine ligand 2 (CCL2), and C-X-C motif chemokine ligand (CXCL) 8 in LPS-activated BEAS-2B cells. The mechanism study revealed that it suppressed the phosphorylation and degradation of IκBα, consequently hindering the translocation of p65 from the cytoplasm to the nucleus and its subsequent binding to DNA, thereby decreasing NF-κB-regulated gene transcription. Notably, scutellarein had no impact on the activation of AP-1 signaling. In LPS-induced ALI mice, scutellarein significantly decreased IL-6, CCL2, and tumor necrosis factor-α (TNF-α) levels in the bronchoalveolar lavage fluid, attenuated lung injury, and inhibited neutrophil infiltration. Our findings suggest that scutellarein may be a beneficial agent for the treatment of infectious pneumonia by virtue of its anti-oxidative and anti-inflammatory activities. Full article

Psychosis, defined as a set of symptoms that results in a distorted sense of reality, is observed in several psychiatric disorders in addition to schizophrenia. This paper reviews the literature relevant to the underlying neurobiology of psychosis. The dopamine hypothesis has been a major influence in the study of the neurochemistry of psychosis and in development of antipsychotic drugs. However, it became clear early on that other factors must be involved in the dysfunction involved in psychosis. In the current review, it is reported how several of these factors, namely dysregulation of neurotransmitters [dopamine, serotonin, glutamate, and γ-aminobutyric acid (GABA)], neuroinflammation, glia (microglia, astrocytes, and oligodendrocytes), the hypothalamic–pituitary–adrenal axis, the gut microbiome, oxidative stress, and mitochondrial dysfunction contribute to psychosis and interact with one another. Research on psychosis has increased knowledge of the complexity of psychotic disorders. Potential new pharmacotherapies, including combinations of drugs (with pre- and probiotics in some cases) affecting several of the factors mentioned above, have been suggested. Similarly, several putative biomarkers, particularly those related to the immune system, have been proposed. Future research on both pharmacotherapy and biomarkers will require better-designed studies conducted on an all stages of psychotic disorders and must consider confounders such as sex differences and comorbidity. Full article

Lycium barbarum, commonly recognized as goji berry or wolfberry, is highly appreciated not only for its organoleptic and nutritional properties but also as an important source of bioactive compounds such as polysaccharides, carotenoids, phenolics, and various other non-nutritive compounds. These constituents give it a multitude of health benefits, including antioxidant, anti-inflammatory, and anticancer properties. However, the precise biochemical mechanisms responsible for its anticancer effects remain unclear, and the comprehensive composition of goji berry extracts is often insufficiently explored. This study aimed to investigate the biochemical pathways modulated in breast cancer cells by an ethanolic extract of Lycium barbarum fruit (LBE). Following metabolomic profiling using UHPLC-HRMS/MS, we assessed the antitumoral properties of LBE on different breast cancer cell lines. This investigation revealed that LBE exhibited cytotoxic effects, inducing a pro-oxidant effect that triggered pyroptosis activation through endoplasmic reticulum (ER) stress and subsequent activation of the P-IRE1α/XBP1/NLRP3 axis in MCF-7 cells. In addition, LBE did not display cytotoxicity toward healthy human cells but demonstrated antioxidant properties by neutralizing ROS generated by doxorubicin. These findings underscore the potential of LBE as a highly promising natural extract in cancer therapy. Full article

In this research, bio-based films were developed using polyelectrolyte complexes derived from chitosan and gelatin for packaging fish oil. To further enhance the antioxidant functionality, the films were enriched with gallic acid and orange essential oils, either individually or in combination. Initially, the films were characterized for their physico-chemical, optical, surface, and barrier properties. Subsequently, the phenolic compounds and antioxidant capacity of the films were assessed. Finally, the films were tested as antioxidant cover lids for packaging fish oil, which was then stored at ambient temperature for 30 days, with periodical monitoring of oil oxidation parameters. This study revealed that the inclusion of gallic acid-induced possible crosslinking effects, as evidenced by changes in moisture content, solubility, and liquid absorption. Additionally, shifts in the FTIR spectral bands suggested the binding of gallic acid and/or phenols in orange essential oils to CSGEL polymer chains, with noticeable alterations in film coloration. Notably, films containing gallic acid exhibited enhanced UV barrier properties crucial for preserving UV-degradable food compounds. Moreover, formulations with gallic acid demonstrated decreased water vapor permeability, while samples containing orange essential oils had lower CO₂ permeability levels. Importantly, formulations containing both gallic acid and essential oils showed a synergistic effect and a significant antioxidant capacity, with remarkable DPPH inhibition rates of up to 88%. During the 30-day storage period, fish oil experienced progressive oxidation, as indicated by an increase in the K232 value in control samples. However, films incorporating gallic acid or orange essential oils as active antioxidants, even used as indirect food contact, effectively delayed the oxidation, highlighting their protective benefits. This study underscores the potential of sustainable bio-based films as natural antioxidant packaging for edible fish oil or fresh fish, offering a promising tool for enhancing food preservation while reducing its waste. Full article

α-lipoic acid is a naturally occurring compound with potent antioxidant properties that helps protect cells and tissues from oxidative stress. Its incorporation into nanoplatforms can affect factors like bioavailability, stability, reactivity, and targeted delivery. Nanoformulations of α-lipoic acid can significantly enhance its solubility and absorption, making it more bioavailable. While α-lipoic acid can be prone to degradation in its free form, encapsulation within nanoparticles ensures its stability over time, and its release in a controlled and sustained manner to the targeted tissues and cells. In addition, α-lipoic acid can be combined with other compounds, such as other antioxidants, drugs, or nanomaterials, to create synergistic effects that enhance their overall therapeutic benefits or hinder their potential cytotoxicity. This review outlines the advantages and drawbacks associated with the use of α-lipoic acid, as well as various nanotechnological approaches employed to enhance its therapeutic effectiveness, whether alone or in combination with other bioactive agents. Furthermore, it describes the engineering of α-lipoic acid to produce poly(α-lipoic acid) nanoparticles, which hold promise as an effective drug delivery system. Full article

Oxidative stress and apoptosis cell death are critical secondary damage mechanisms that lead to losing neighboring healthy tissue after cerebral ischemia. This study aims to characterize the type of interaction between dapsone (DDS) and cannabidiol (CBD) and its cytoprotective effect in an in vitro model of oxygen and glucose deprivation for 6 h followed by 24 h of reoxygenation (OGD/R), using the SH-SY5Y cell line. For the combined concentrations, an isobolographic study was designed to determine the optimal concentration–response combinations. Cell viability was evaluated by measuring the lactate dehydrogenase (LDH) release and 3-[4, 5-dimethyl-2-thiazolyl]-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assays. Also, the reactive oxygen species (ROS) and reduced glutathione (GSH) levels were analyzed as oxidative stress markers. Finally, caspase-3 activity was evaluated as a marker cell death by apoptosis. The results showed a decrease in cell viability, an increase in oxidant stress, and the activity of caspase-3 by the effect of OGD/R. Meanwhile, both DDS and CBD demonstrated antioxidant, antiapoptotic, and cytoprotective effects in a concentration–response manner. The isobolographic study indicated that the concentration of 2.5 µM of DDS plus 0.05 µM of CBD presented a synergistic effect so that in treatment, cell death due to OGD/R decreased. The findings indicate that DDS–CBD combined treatment may be a helpful therapy in cerebral ischemia with reperfusion. Full article

Many countries, including Japan, are experiencing declining birth rates. Assisted reproductive technologies have consistently demonstrated good results in resolving infertility. Although the development of fertilized eggs into blastocysts has been recognized as a crucial step in assisted reproductive technologies, the involved mechanisms are currently unclear. Here, we established a new culture system for the in vitro development of fertilized eggs into blastocysts. In the Transwell culture system, the rate of blastocysts hatching from fertilized eggs cultured with adipose-derived stem cells (ASCs) was significantly higher than that of blastocysts cultured only with fertilized eggs. Gene ontology analysis revealed that the developed blastocysts displayed essential gene expression patterns in mature blastocysts. Additionally, when cultured with 3rd-passage ASCs, the developed blastocysts expressed the core genes for blastocyst maturation and antioxidant properties compared to those cultured only with fertilized eggs or cultured with 20th-passage ASCs. These results suggest that the Transwell culture system may imitate the in vivo tubal culture state for fertilized eggs. Exosomes derived from stem cells with stemness potential play a powerful role in the development of blastocysts from fertilized eggs. Additionally, the exosomes expressed specific microRNAs; therefore, the Transwell culture system resulted in a higher rate of pregnancy. In future, the extraction of their own extracellular vesicles from the culture medium might contribute to the development of novel assisted reproductive technologies. Full article

Limosilactobacillus fermentum (L. fermentum) is widely used in industrial food fermentations, and its probiotic and health-promoting roles attracted much attention in the past decades. In this work, the probiotic potential of L. fermentum 664 isolated from Chinese fermented pickles was assessed. In addition, the anti-inflammatory properties and mechanisms were investigated using lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Results indicated that L. fermentum 664 demonstrated excellent acid and bile salt tolerance, adhesion capability, antimicrobial activity, and safety profile. L. fermentum 664 downregulated the release of inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and cyclooxygenase-2 (COX-2) stimulated with LPS. Moreover, L fermentum 664 inhibited the nuclear translocation of the nuclear factor κB (NF-κB) and the activation of mitogen-activated protein kinases (MAPKs) induced by LPS. This action was associated with a reduction in reactive oxygen species (ROS) levels and an enhanced expression of heme oxygenase-1 (HO-1) protein. Additionally, whole genome sequencing indicated that L. fermentum 664 contained genes that encode proteins with antioxidant and anti-inflammatory functions, including Cytochrome bd ubiquinol oxidase subunit I (CydA), Cytochrome bd ubiquinol oxidase subunit II (CydB), and NAD(P)H dehydrogenase quinone 1 (NQO1). In conclusion, our study suggested that L. fermentum 664 has the potential to become a probiotic and might be a promising strategy for the prevention of inflammation. Full article

Repetitive motion or exercise is associated with oxidative stress and muscle inflammation, which can lead to declining grip strength and muscle damage. Oleanolic acid and ursolic acid have anti-inflammatory and antioxidant properties and can be extracted from Chaenomeles speciosa through ultrasonic sonication. We investigated the association between grip strength declines and muscle damage induced by lambda carrageenan (LC) injection and exercise exposure in rats. We also assessed the reparative effects of transdermal pretreatment and post-treatment with C. speciosa extracts (CSEs) by using a supersonic atomizer. The half-maximal inhibitory concentration (IC₅₀) of CSEs for cells was 10.5 mg/mL. CSEs significantly reduced the generation of reactive oxygen species and inflammatory factors (interleukin [IL]-6 and IL-1β) in in vitro cell tests. Rats subjected to LC injection and 6 weeks of exercise exhibited significantly increased inflammatory cytokine levels (IL-1β, TNF-α, and IL-6). Hematoxylin and eosin staining revealed inflammatory cell infiltration and evident muscle damage in the gastrocnemius muscle, which exhibited splitting and the appearance of the endomysium and perimysium. The treated rats’ grip strength significantly declined. Following treatment with CSEs, the damaged muscles exhibited decreased IL-1β, TNF-α, and IL-6 levels and normal morphologies. Moreover, grip strength significantly recovered. Pretreatment with CSEs yielded an immediate and significant increase in grip strength, with an increase of 180% and 165% occurring in the rats exposed to LC injection and exercise within the initial 12 h period, respectively, compared with the control group. Pretreatment with CSEs delivered transdermally using a supersonic atomizer may have applications in sports medicine and training or competitions. Full article

With neurodegenerative disorders being on the rise, a great deal of research from multiple fields is being conducted in order to further knowledge and propose novel therapeutic interventions. Among these investigations, research on the role of antioxidants in contrasting cognitive decline is putting forward interesting and promising results. In this review, we aim to collect evidence that focused on the role of a variety of antioxidants and antioxidant-rich foods in improving or stabilizing cognitive functions, memory, and Alzheimer’s disease, the most common neurodegenerative disorder. Specifically, we considered evidence collected on humans, either through longitudinal studies or randomized, placebo-controlled ones, which evaluated cognitive performance, memory abilities, or the progression level of neurodegeneration. Overall, despite a great deal of variety between study protocols, cohorts of participants involved, neuropsychological tests used, and investigated antioxidants, there is a solid trend that suggests that the properties of antioxidants may be helpful in hampering cognitive decline in older people. Thus, the help of future research that will further elucidate the role of antioxidants in neuroprotection will lead to the development of novel interventions that will take into account such findings to provide a more global approach to treating neurodegenerative disorders. Full article

The importance of gamma-aminobutyric acid (GABA) in plants has been highlighted due to its critical role in mitigating metal toxicity, specifically countering the inhibitory effects of copper stress on rice plants. This study involved pre-treating rice plants with 1 mM GABA for one week, followed by exposure to varying concentrations of copper at 50 μM, 100 μM, and 200 μM. Under copper stress, particularly at 100 μM and 200 μM, plant height, biomass, chlorophyll content, relative water content, mineral content, and antioxidant activity decreased significantly compared to control conditions. However, GABA treatment significantly alleviated the adverse effects of copper stress. It increased plant height by 13%, 18%, and 32%; plant biomass by 28%, 52%, and 60%; chlorophyll content by 12%, 30%, and 24%; and relative water content by 10%, 24%, and 26% in comparison to the C50, C100, and C200 treatments. Furthermore, GABA treatment effectively reduced electrolyte leakage by 11%, 34%, and 39%, and the concentration of reactive oxygen species, such as malondialdehyde (MDA), by 9%, 22%, and 27%, hydrogen peroxide (H₂O₂) by 12%, 38%, and 30%, and superoxide anion content by 8%, 33, and 39% in comparison to C50, C100, and C200 treatments. Additionally, GABA supplementation led to elevated levels of glutathione by 69% and 80%, superoxide dismutase by 22% and 125%, ascorbate peroxidase by 12% and 125%, and catalase by 75% and 100% in the C100+G and C200+G groups as compared to the C100 and C200 treatments. Similarly, GABA application upregulated the expression of GABA shunt pathway-related genes, including gamma-aminobutyric transaminase (OsGABA-T) by 38% and 80% and succinic semialdehyde dehydrogenase (OsSSADH) by 60% and 94% in the C100+G and C200+G groups, respectively, as compared to the C100 and C200 treatments. Conversely, the expression of gamma-aminobutyric acid dehydrogenase (OsGAD) was downregulated. GABA application reduced the absorption of Cu²⁺ by 54% and 47% in C100+G and C200+G groups as compared to C100, and C200 treatments. Moreover, GABA treatment enhanced the uptake of Ca²⁺ by 26% and 82%, Mg²⁺ by 12% and 67%, and K⁺ by 28% and 128% in the C100+G and C200+G groups as compared to C100, and C200 treatments. These findings underscore the pivotal role of GABA-induced enhancements in various physiological and molecular processes, such as plant growth, chlorophyll content, water content, antioxidant capacity, gene regulation, mineral uptake, and copper sequestration, in enhancing plant tolerance to copper stress. Such mechanistic insights offer promising implications for the advancement of safe and sustainable food production practices. Full article

Because of its high antioxidant activity, chokeberry can be used both in the prevention and treatment of various metabolic disorders. In this study, for the first time, the synergistic effects of chokeberry juice and chokeberry fiber on selected metabolic and anthropometric parameters were assessed during a 90-day intervention including 102 people (67 women and 35 men). After 60 days of intervention with chokeberry juice, statistically significant increases in the muscle mass and antioxidant potential of the serum were observed. In turn, there were decreases in the waist circumference, systolic blood pressure, diastolic blood pressure, heart rate, glycated hemoglobin, glucose, LDL cholesterol, eGFR, and ALT level. The addition of chokeberry fiber for the next 30 days resulted in stabilizations of the diastolic blood pressure, glycated hemoglobin, glucose, and waist circumference, as well as reductions in the values of the heart rate, LDL cholesterol, insulin, and AST level. After 90 days, a significant increase in the FRAP value was also observed. This intervention indicates that chokeberry products may have a beneficial effect on metabolic health and serve as a foundation for developing functional foods. Full article

Bronchopulmonary dysplasia (BPD) is a chronic condition affecting preterm infants, characterized by lung alveolar simplification/hypoalveolarization and vascular remodeling. The nuclear factor erythroid 2 like 2 (Nfe2l2, or Nrf2) plays a critical role in the cytoprotective response to neonatal hyperoxia, and its global deficiency exacerbates hypoalveolarization in mice. The abnormal recruitment and activation of myeloid cells are associated with the pathogenesis of BPD. Therefore, we employed a genetic approach to investigate the role of myeloid Nrf2 in regulating hyperoxia-induced hypoalveolarization. Pups, both wild-type (Nrf2^f/f) and those with a myeloid Nrf2 deletion (abbreviated as Nrf2^∆/∆mye), were exposed to hyperoxia for 72 h at postnatal day 1 (Pnd1), and then sacrificed at either Pnd4 or Pnd18 following a two-week recovery period. We analyzed the hypoalveolarization, inflammation, and gene expression related to cytoprotective and inflammatory responses in the lungs of these pups. The hypoalveolarization induced by hyperoxia was significantly greater in Nrf2^∆/∆mye pups compared to their Nrf2^f/f counterparts (35.88% vs. 21.01%, respectively) and was accompanied by increased levels of inflammatory cells and IL-1β activation in the lungs. Antioxidant gene expression in response to neonatal hyperoxia was lower in Nrf2^∆/∆mye pups compared to their Nrf2^f/f counterparts. Furthermore, Nrf2-deficient macrophages exposed to hyperoxia exhibited markedly decreased cytoprotective gene expression and increased IL-1β levels compared to Nrf2-sufficient cells. Our findings demonstrate the crucial role of myeloid Nrf2 in mitigating hyperoxia-induced lung hypoalveolarization and inflammatory responses in neonatal mice. Full article

Glutathione (GSH), a prominent antioxidant in organisms, exhibits diverse biological functions and is crucial in safeguarding cells against oxidative harm and upholding a stable redox milieu. The metabolism of GSH is implicated in numerous diseases, particularly in the progression of malignant tumors. Consequently, therapeutic strategies targeting the regulation of GSH synthesis and metabolism to modulate GSH levels represent a promising avenue for future research. This study aimed to elucidate the intricate relationship between GSH metabolism and ferroptosis, highlighting how modulation of GSH metabolism can impact cellular susceptibility to ferroptosis and consequently influence the development of tumors and other diseases. The paper provides a comprehensive overview of the physiological functions of GSH, including its structural characteristics, physicochemical properties, sources, and metabolic pathways, as well as investigate the molecular mechanisms underlying GSH regulation of ferroptosis and potential therapeutic interventions. Unraveling the biological role of GSH holds promise for individuals afflicted with tumors. Full article

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) represents the master regulator of the cellular antioxidant response and plays a critical role in tumorigenesis. This includes a preventive effect of Nrf2 on cell death through ferroptosis, which represents an essential mechanism of therapy resistance in malignant tumors, such as pancreatic ductal adenocarcinoma (PDAC) as one of the most aggressive and still incurable tumors. Addressing this issue, we provide an overview on Nrf2 mediated antioxidant response with particular emphasis on its effect on mitochondria as the organelle responsible for the execution of ferroptosis. We further outline how deregulated Nrf2 adds to the progression and therapy resistance of PDAC, especially with respect to the role of ferroptosis in anti-cancer drug mediated cell killing and how this is impaired by Nrf2 as an essential mechanism of drug resistance. Our review further discusses recent approaches for Nrf2 inhibition by natural and synthetic compounds to overcome drug resistance based on enhanced ferroptosis. Finally, we provide an outlook on therapeutic strategies based on Nrf2 inhibition combined with ferroptosis inducing drugs. Full article

This explorative study aimed to assess the mutagenicity and genotoxicity of stored-cooked beef patties formulated with and without phenols (7.00 mg of phenols/80-g patty) extracted from olive vegetation water (OVW), as related to the formation of cholesterol oxidation products (COPs) and heterocyclic amines (HCAs). The patties were packaged in a modified atmosphere, sampled during cold storage (4 °C) for 9 days, and grilled at 200 °C. The genotoxicity was evaluated by the Comet assay. The patty extract was found to be genotoxic on primary peripheral blood mononuclear cells (PBMCs), while no mutagenicity was detected. The addition of OVW phenols significantly decreased the genotoxicity of the patty extract and reduced the total COPs content in stored-cooked patties (4.59 times lower than control); however, it did not affect the content of total HCAs (31.51–36.31 ng/patty) and the revertants’ number. Therefore, these results demonstrate that the OVW phenols were able to counteract the formation of genotoxic compounds in stored-cooked beef patties. Full article

In the light of growing concerns faced by Western societies due to aging, natality decline, and epidemic of cardio-metabolic diseases, both preventable and treatable, new and effective strategical interventions are urgently needed in order to decrease their socio-economical encumbrance. The recent focus of research has been redirected towards investigating the potential of haskap (Lonicera caerulea L.) as a novel functional food or superfruit. Therefore, our present review aims to highlight the latest scientific proofs regarding the potential of Lonicera caerulea L. (LC), a perennial fruit-bearing plant rich in polyphenols, in reversing cardio-metabolic dysfunctions. In this regard, a systematic search on two databases (PubMed and Google Scholar) from 1 January 2016 to 1 December 2023 was performed, the keyword combination being Lonicera caerulea L. AND the searched pharmacological action, with the inclusion criteria consisting of in extenso original articles, written in English. The health-enhancing characteristics of haskap berries have been examined through in vitro and in vivo studies from the 35 included original papers. Positive effects regarding cardiovascular diseases and metabolic syndrome have been assigned to the antioxidant activity, hypolipidemic and hypoglycemic effects, as well as to the hepatoprotective and vasoprotective potential. Latest advances regarding LCF mechanisms of action are detailed within this review as well. All these cutting-edge data suggest that this vegetal product would be a good candidate for further clinical studies. Full article

Cell death involving oxidative stress and mitochondrial dysfunction is a major cause of dopaminergic neuronal loss in the substantia nigra (SN) of Parkinson’s disease patients. Ergothioneine (ET), a natural dietary compound, has been shown to have cytoprotective functions, but neuroprotective actions against PD have not been well established. 6-Hydroxydopamine (6-OHDA) is a widely used neurotoxin to simulate the degeneration of dopaminergic (DA) neurons in Parkinson’s disease. In this study, we investigated the protective effect of ET on 6-OHDA treated iPSC-derived dopaminergic neurons (iDAs) and further confirmed the protective effects in 6-OHDA-treated human neuroblastoma SH-SY5Y cells. In 6-OHDA-treated cells, decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial reactive oxygen species (mROS), reduced cellular ATP levels, and increased total protein carbonylation levels were observed. 6-OHDA treatment also significantly decreased tyrosine hydroxylase levels. These effects were significantly decreased when ET was present. Verapamil hydrochloride (VHCL), a non-specific inhibitor of the ET transporter OCTN1 abrogated ET’s cytoprotective effects, indicative of an intracellular action. These results suggest that ET could be a potential therapeutic for Parkinson’s disease. Full article