The heavy metal contamination in plant-soil environment has increased manifold recently. In order to reduce the harmful effects of metal stress in plants, the application of beneficial soil microbes is gaining much attention. In the present research, the role of Serratia marcescens BM1 in enhancing cadmium (Cd) stress tolerance and phytoremediation potential of soybean plants, was investigated. Exposure of soybean plants to two Cd doses (150 and 300 µM) significantly reduced plant growth, biomass, gas exchange attributes, nutrients uptake, antioxidant capacity, and the contents of chlorophyll, total phenolics, flavonoids, soluble sugars, and proteins. Additionally, Cd induced the stress levels of Cd, proline, glycine betaine, hydrogen peroxide, malondialdehyde, antioxidant enzymes (i.e., catalase, CAT; ascorbate peroxidase, APX; superoxide dismutase, SOD; peroxidise, POD), and the expression of stress-related genes (i.e., APX, CAT, Fe-SOD, POD, CHI, CHS, PHD2, VSO, NR, and P5CS) in soybean leaves. On the other hand, inoculation of Cd-stressed soybean plants with Serratia marcescens BM1 significantly enhanced the plant growth, biomass, gas exchange attributes, nutrients uptake, antioxidant capacity, and the contents of chlorophyll, total phenolics, flavonoids, soluble sugars, and proteins. Moreover, Serratia marcescens BM1 inoculation reduced the levels of cadmium and oxidative stress markers, but significantly induced the activities of antioxidant enzymes and the levels of osmolytes and stress-related genes expression in Cd-stressed plants. The application of 300 µM CdCl₂ and Serratia marcescens triggered the highest expression levels of stress-related genes. Overall, this study suggests that inoculation of soybean plants with Serratia marcescens BM1 promotes phytoremediation potential and Cd stress tolerance by modulating the photosynthetic attributes, osmolytes biosynthesis, antioxidants machinery, and the expression of stress-related genes. Full article

Hibiscus syriacus L. is distributed widely throughout Eastern and Southern Asia and considered as the national flower of South Korea. The extraction of several plant parts of H. syriacus L. is currently used as a natural remedy for several diseases, including breast and lung cancer, microbial infection, and chronic inflammation. However, the effect of the anthocyanin extract of H. syriacus L. petals (PS) in oxidative stress conditions has not been studied. In this study, we evaluated the cytoprotective effect of PS against H₂O₂-induced oxidative stress in HaCaT keratinocytes. In this study, we found that PS significantly inhibited H₂O₂-induced apoptosis of HaCaT keratinocytes. We also revealed that PS mediated-cytoprotective effect was associated with the increased expression of heme oxygenase-1 (HO-1) arising from the activation of nuclear factor erythroid 2-related factor-2 (Nrf2). PS also decreased H₂O₂-induced excessive intracellular ROS generation and restored H₂O₂-induced mitochondrial depolarization through the downregulation of mitochondrial ROS production. Furthermore, H₂O₂-induced Bax and caspase-3 expression was markedly abolished in the presence of PS. The inhibition of HO-1 by zinc protoporphyrin significantly attenuated the cytoprotective effect of PS in H₂O₂-treated HaCaT keratinocytes along with ROS generation, indicating that HO-1 crucially affects PS-mediated cytoprotective properties. Collectively, our results suggested that, under H₂O₂-mediated oxidative stress conditions, PS sustained a normal level of mitochondrial membrane potential and ROS generation in HaCaT keratinocytes by activating the Nrf2/HO-1 axis, exerting cytoprotective effects against oxidative stress. Full article

This review focuses on the conditions required to increase and maintain the antioxidant nutrients in both extra virgin olive oil (EVOO) and table olives (TOs) from the agronomic and technological practices to the gastronomy. The main antioxidants of TOs and EVOO are phenol alcohols and acids, secoiridoids, lignans and flavones, all of which possess the ability to prolong the oil’s shelf-life and exhibit healthy properties for humans. The precise detection of secoiridoid derivatives remains the breakthrough for the nutritional and health quality certification of extra virgin olive oils (EVOOs) required for EFSA health claims. To attain the necessary antioxidant quality in both EVOO and TOs, it is necessary to hard focus on the several steps in the production chain, including olive cultivar, agronomic conditions, harvesting methods, and transformation technology. The quality level is maintained if the storage conditions aim to minimize the oxidative processes that occur due to oxygen and light. In terms of minor polar biophenols, there is disagreement on which between the organic or conventional EVOOs show higher concentration values. The strict disciplinary of production of protected designation EVOOs does not ensure higher phenol values in comparison to the artisanal EVOOs. In gastronomy, the EVOOs are preferable to seed oils, particularly during frying vegetable. The EVOOs show higher heat stability, linked both to the fatty acid composition and the phenol content, that is important for preventing fatty acids oxidation. Concerning TOs, the commercial presentation includes olives and olive paste. Both products show a remarkable loss of natural antioxidants after pasteurization and during storage as the thermal treatment mostly impacts on TOs secoiridoids. Full article

Obesity is a risk factor for vascular dysfunction and insulin resistance. The study aim was to demonstrate that adipocyte-specific HO-1 (heme oxygenase-1) gene therapy is a therapeutic approach for preventing the development of obesity-induced metabolic disease in an obese-mice model. Specific expression of HO-1 in adipose tissue was achieved by using a lentiviral vector expressing HO-1 under the control of the adiponectin vector (Lnv-adipo-HO-1). Mice fed a high-fat diet (HFD) developed adipocyte hypertrophy, fibrosis, decreased mitochondrial respiration, increased levels of inflammatory adipokines, insulin resistance, vascular dysfunction, and impaired heart mitochondrial signaling. These detrimental effects were prevented by the selective expression of HO-1 in adipocytes. Lnv-adipo-HO-1-transfected mice on a HFD display increased cellular respiration, increased oxygen consumption, increased mitochondrial function, and decreased adipocyte size. Moreover, RNA arrays confirmed that targeting adipocytes with HO-1 overrides the genetic susceptibility of adiposopathy and correlated with restoration of the expression of anti-inflammatory, thermogenic, and mitochondrial genes. Our data demonstrate that HO-1 gene therapy improved adipose tissue function and had positive impact on distal organs, suggesting that specific targeting of HO-1 gene therapy is an attractive therapeutic approach for improving insulin sensitivity, metabolic activity, and vascular function in obesity. Full article

Accumulating evidence suggests that the pineal hormone melatonin displays protective effects against renal fibrosis, but the mechanisms remain poorly understood. Here, we investigate the effect of the pineal hormone on transdifferentiation of renal fibroblasts to myofibroblasts invoked by transforming growth factor-β1 (TGF-β1). Increased proliferation and activation of renal interstitial fibroblasts after TGF-β1 treatment were attenuated by melatonin pretreatment. Mechanistically, melatonin suppressed Smad2/3 phosphorylation and nuclear co-localization of their phosphorylated forms and Smad4 after TGF-β1 stimulation. In addition, increased phosphorylations of Akt, extracellular signal-regulated kinase 1/2, and p38 after TGF-β1 treatment were also suppressed by the hormone. These effects of melatonin were not affected by pharmacological and genetic inhibition of its membrane receptors. Furthermore, melatonin significantly reversed an increase of intracellular reactive oxygen species (ROS) and malondialdehyde levels, and a decrease of the reduced glutathione/oxidized glutathione ratio after TGF-β1 treatment. Finally, TGF-β1-induced proliferation and activation were also suppressed by N-acetylcysteine. Altogether, these findings suggest that the pineal hormone melatonin prevents TGF-β1-induced transdifferentiation of renal interstitial fibroblasts to myofibroblasts via inhibition of Smad and non-Smad signaling cadcades by inhibiting ROS-mediated mechanisms in its receptor-independent manner. Full article

Hypothermia enhances outcomes of patients after resuscitation after cardiac arrest (CA). However, the underlying mechanism is not fully understood. In this study, we investigated effects of hypothermic therapy on neuronal damage/death, microglial activation, and changes of endogenous antioxidants in the anterior horn in the lumbar spinal cord in a rat model of asphyxial CA (ACA). A total of 77 adult male Sprague–Dawley rats were randomized into five groups: normal, sham ACA plus (+) normothermia, ACA + normothermia, sham ACA + hypothermia, and ACA + hypothermia. ACA was induced for 5 min by injecting vecuronium bromide. Therapeutic hypothermia was applied after return of spontaneous circulation (ROSC) via rapid cooling with isopropyl alcohol wipes, which was maintained at 33 ± 0.5 °C for 4 h. Normothermia groups were maintained at 37 ± 0.2 °C for 4 h. Neuronal protection, microgliosis, oxidative stress, and changes of endogenous antioxidants were evaluated at 12 h, 1 day, and 2 days after ROSC following ACA. ACA resulted in neuronal damage from 12 h after ROSC and evoked obvious degeneration/loss of spinal neurons in the ventral horn at 1 day after ACA, showing motor deficit of the hind limb. In addition, ACA resulted in a gradual increase in microgliosis with time after ACA. Therapeutic hypothermia significantly reduced neuronal loss and attenuated hind limb dysfunction, showing that hypothermia significantly attenuated microgliosis. Furthermore, hypothermia significantly suppressed ACA-induced increases of superoxide anion production and 8-hydroxyguanine expression, and significantly increased superoxide dismutase 1 (SOD1), SOD2, catalase, and glutathione peroxidase. Taken together, hypothermic therapy was found to have a substantial impact on changes in ACA-induced microglia activation, oxidative stress factors, and antioxidant enzymes in the ventral horn of the lumbar spinal cord, which closely correlate with neuronal protection and neurological performance after ACA. Full article

Parkinson’s disease (PD) is a neurodegenerative disease, which is associated with mitochondrial dysfunction and abnormal protein accumulation. No treatment can stop or slow PD. Autophagy inhibits neuronal death by removing damaged mitochondria and abnormal protein aggregations. Celastrol is a triterpene with antioxidant and anti-inflammatory effects. Up until now, no reports have shown that celastrol improves PD motor symptoms. In this study, we used PD cell and mouse models to evaluate the therapeutic efficacy and mechanism of celastrol. In the substantia nigra, we found lower levels of autophagic activity in patients with sporadic PD as compared to healthy controls. In neurons, celastrol enhances autophagy, autophagosome biogenesis (Beclin 1↑, Ambra1↑, Vps34↑, Atg7↑, Atg12↑, and LC3-II↑), and mitophagy (PINK1↑, DJ-1↑, and LRRK2↓), and these might be associated with MPAK signaling pathways. In the PD cell model, celastrol reduces MPP⁺-induced dopaminergic neuronal death, mitochondrial membrane depolarization, and ATP reduction. In the PD mouse model, celastrol suppresses motor symptoms and neurodegeneration in the substantia nigra and striatum and enhances mitophagy (PINK1↑ and DJ-1↑) in the striatum. Using MPP⁺ to induce mitochondrial damage in neurons, we found celastrol controls mitochondrial quality by sequestering impaired mitochondria into autophagosomes for degradation. This is the first report to show that celastrol exerts neuroprotection in PD by activating mitophagy to degrade impaired mitochondria and further inhibit dopaminergic neuronal apoptosis. Celastrol may help to prevent and treat PD. Full article

Neuroinflammation is a common feature shared by neurodegenerative disorders, such as Parkinson’s disease (PD), and seems to play a key role in their development and progression. Microglia cells, the principal orchestrators of neuroinflammation, can be polarized in different phenotypes, which means they are able to have anti-inflammatory, pro-inflammatory, or neurodegenerative effects. Increasing evidence supports that the traditional Mediterranean dietary pattern is related to the reduction of cognitive decline in neurodegenerative diseases. A considerable intake of plant foods, fish, and extra virgin olive oil (EVOO), as well as a moderate consumption of red wine, all characteristic of the Mediterranean diet (MD), are behind these effects. These foods are especially rich in polyphenols, being the most relevant in the MD hydroxytyrosol (HT) and their derivatives present in EVOO, which have demonstrated a wide array of biological activities. Here, we demonstrate that HT is able to reduce the inflammation induced by two different stimuli: lipopolysaccharide and α-synuclein. We also study the possible molecular mechanisms involved in the anti-inflammatory effect of HT, including the study of nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPKs), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, and inflammasome. Our data support the use of HT to prevent the inflammation associated with PD and shed light into the relationship between MD and this neurological disorder. Full article

In this review, special emphasis will be placed on red grape polyphenols for their antioxidant and anti-inflammatory activities. Therefore, their capacity to inhibit major pathways responsible for activation of oxidative systems and expression and release of proinflammatory cytokines and chemokines will be discussed. Furthermore, regulation of immune cells by polyphenols will be illustrated with special reference to the activation of T regulatory cells which support a tolerogenic pathway at intestinal level. Additionally, the effects of red grape polyphenols will be analyzed in obesity, as a low-grade systemic inflammation. Also, possible modifications of inflammatory bowel disease biomarkers and clinical course have been studied upon polyphenol administration, either in animal models or in clinical trials. Moreover, the ability of polyphenols to cross the blood–brain barrier has been exploited to investigate their neuroprotective properties. In cancer, polyphenols seem to exert several beneficial effects, even if conflicting data are reported about their influence on T regulatory cells. Finally, the effects of polyphenols have been evaluated in experimental models of allergy and autoimmune diseases. Conclusively, red grape polyphenols are endowed with a great antioxidant and anti-inflammatory potential but some issues, such as polyphenol bioavailability, activity of metabolites, and interaction with microbiota, deserve deeper studies. Full article

Thymus mastichina, also called mastic thyme or Spanish marjoram, is endemic to the Iberian Peninsula, where it is widely used in folk medicine especially for treating digestive and respiratory systems disorders, and as a condiment to season olives. This work describes for the first time the detailed phenolic composition of exhaustive hydroethanolic extracts and aqueous decoctions of Thymus mastichina. Unlike other species of the Thymus genera, Thymus mastichina extracts contain high amounts of salvianolic acid derivatives, with salvianolic acid A isomer being the main derivative. This isomer was identified in extracts from Thymus mastichina for the first time. Also, an undescribed salvianolic acid derivative in Thymus mastichina was identified and its structure was tentatively described. Extracts from Thymus mastichina showed significant scavenging activity of 2,2-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical cation, hydroxyl, and nitric oxide radicals. The anti-proliferative effect of both T. mastichina extracts were tested against Caco-2 and HepG2 cells; the hydroethanolic extract showed a high anti-proliferative activity against Caco-2 cells compared to HepG2 cells (at 24 h exposure, the concentration that inhibits 50% of proliferation, IC₅₀, was 71.18 ± 1.05 µg/mL and 264.60 ± 11.78 µg/mL for Caco-2 and HepG2, respectively). Thus, these results make this species a promising candidate for further investigation of its anti-tumoral potential. Therefore, Thymus mastichina can be potentially used as a functional food (used as a decoction or herbal tea) or as a source of bioactive ingredients with antioxidant and anti-proliferative properties. Full article

This study was undertaken to determine the phenolic compounds and the anti-atherogenic effect of bee bread in high-fat diet (HFD)-induced obese rats. The presence of phenolic compounds in bee bread was determined by liquid chromatography–mass spectrometry. Thirty-two male Sprague Dawley rats were divided into four groups, (n = 8/group); i.e., Normal (N), HFD (high-fat diet), HFD + BB (high-fat diet and 0.5 g/kg/day bee bread), and HFD + O (high-fat diet and 10 mg/kg/day orlistat) groups. After 6 weeks of the experiment, rats were sacrificed. Five phenolic compounds were identified in bee bread; namely, caffeic acid, ferulic acid, kaempferol, apigenin, and isorhamnetin. Bee bread significantly reduced Lee obesity index and levels of total cholesterol (TC), low-density lipoprotein (LDL), fatty acid synthase (FAS) activity, atherogenic index, oxidised-LDL (oxLDL), and malondialdehyde (MDA), and significantly increased aortic antioxidant activities, such as those of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Adipocyte sizes were found to be smaller in the HFD + BB group compared to the N group, and en face aortas showed an absence of atherosclerotic plaque in rats supplemented with bee bread. These changes might suggest an anti-atherogenic effect of bee bread in HFD-induced obese rats via its antioxidant and hypocholesterolaemic properties. Full article

Peroxiredoxins (PRDXs) are antioxidant enzymes that protect cells from oxidative stress and play a role in reactive oxygen species (ROS)-mediated signaling. We reported that PRDXs are critical for human fertility by maintaining sperm viability and regulating ROS levels during capacitation. Moreover, studies on Prdx6^−/− mice revealed the essential role of PRDX6 in the viability, motility, and fertility competence of spermatozoa. Although PRDXs are abundant in the testis and spermatozoa, their potential role at different phases of spermatogenesis and in perinatal germ cells is unknown. Here, we examined the expression and role of PRDXs in isolated rat neonatal gonocytes, the precursors of spermatogonia, including spermatogonial stem cells. Gene array, qPCR analyses showed that PRDX1, 2, 3, 5, and 6 transcripts are among the most abundant antioxidant genes in postnatal day (PND) 3 gonocytes, while immunofluorescence confirmed the expression of PRDX1, 2, and 6 proteins. The role of PRDXs in gonocyte viability was examined using PRDX inhibitors, revealing that the 2-Cys PRDXs and PRDX6 peroxidases activities are critical for gonocytes viability in basal condition, likely preventing an excessive accumulation of endogenous ROS in the cells. In contrast to its crucial role in spermatozoa, PRDX6 independent phospholipase A₂ (iPLA₂) activity was not critical in gonocytes in basal conditions. However, under conditions of H₂O₂-induced oxidative stress, all these enzymatic activities were critical to maintain gonocyte viability. The inhibition of PRDXs promoted a two-fold increase in lipid peroxidation and prevented gonocyte differentiation. These results suggest that ROS are produced in neonatal gonocytes, where they are maintained by PRDXs at levels that are non-toxic and permissive for cell differentiation. These findings show that PRDXs play a major role in the antioxidant machinery of gonocytes, to maintain cell viability and allow for differentiation. Full article

Osteoarthritis and its associated comorbidities are important clinical problems that have a negative impact on the quality of life, and its treatment remains unresolved. We investigated whether the systemic administration of slow-releasing hydrogen sulfide (H₂S) donors, allyl isothiocyanate (A-ITC) and phenyl isothiocyanate (P-ITC), alleviates chronic osteoarthritis pain and the associated emotional disorders. In C57BL/6 female mice with osteoarthritis pain induced by the intra-articular injection of monosodium iodoacetate, we evaluated the effects of repeated administration of A-ITC and P-ITC on the (i) mechanical allodynia and grip strength deficits; (ii) emotional conducts; and (iii) glial activity and expression of inducible nitric oxide synthase (NOS2), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt), and antioxidant enzymes (heme oxygenase 1, NAD(P)H:quinone oxidoreductase-1, glutathione S-transferase mu 1 and alpha 1) in the hippocampus. The administration of A-ITC and P-ITC inhibited the mechanical allodynia, the grip strength deficits, and the depressive-like behaviors accompanying osteoarthritis. Both treatments inhibited microglial activation, normalized the upregulation of NOS2 and PI3K/p-Akt, and maintained high levels of antioxidant/detoxificant enzymes in the hippocampus. Data suggest that treatment with low doses of slow-releasing H₂S donors might be an interesting strategy for the treatment of nociception, functional disability, and emotional disorders associated with osteoarthritis pain. Full article

Background: Homocysteine is a sulfur amino acid whose metabolism is activated in two pathways: remethylation to methionine, which requires folate and vitamin B₁₂, and transsulfuration to cystathionine, which needs pyridoxal-5’-phosphate. High homocysteine level increases the risk of developing heart disease, stroke, peripheral vascular diseases, and cognitive impairment. Some evidence showed that exposure to these metals increased plasma homocysteine levels. Methods: A systematic review was carried out to clarify the relationship between homocysteine blood levels and exposure to toxic heavy metals (Lead, Cadmium, Mercury, and Chromium). Results: The results of this systematic review indicate that exposure to Pb, Cr, Cd, and Hg is connected with nonphysiological homocysteine levels or vitamin B₁₂ and folate serum concentrations. Conclusions: These findings reinforce the importance of involvement in exposure to heavy metals in homocysteine metabolism. This supports the role of blood metals as potential upstream modifiable risk factors to prevent the development of other established risk factors as hyperhomocysteinemia. Full article

The purpose of this study was to investigate the effects of acacia polyphenol (AP) supplementation on exercise-induced oxidative stress in mouse liver and skeletal muscle. Plasma aspartate aminotransferase (AST), liver and skeletal muscle levels of thiobarbituric acid reactive substance (TBARS), and levels of skeletal muscle protein carbonyls increased immediately after exhaustive exercise. Exhaustive exercise also decreased liver glutathione (GSH). These results suggest that the exhaustive exercise used in this study induced tissue damage and oxidative stress. Contrary to our expectations, AP supplementation increased plasma AST and alanine aminotransferase activities, liver levels of TBARS, and protein carbonyls. Furthermore, AP supplementation decreased glutathione and glutathione peroxidase activity in the liver. On the other hand, AP supplementation decreased TBARS levels in skeletal muscle. These results suggest that oral high-dose AP administration decreased oxidative stress in skeletal muscle but induced oxidative stress in the liver and increased hepatotoxicity. Full article