Pomegranate contains bioactive compounds in all its parts. In this study, two levels of pomegranate peel byproduct (PPB) with or without the inclusion of xylanase enzyme were used to supplement laying hens’ diet, in a 2 × 2 full factorial design. A total of 48 Isa brown laying hens were fed the following experimental diets for 8 weeks: T1 (2.5% PPB); T2 (2.5% PPB and xylanase); T3 (5% PPB); T4 (5% PPB and xylanase). Eggs collected were analyzed for egg quality parameters. Moreover, egg yolks were analyzed for Malondialdehyde content (MDA), fatty acid profile and total phenolic content. The T2 eggs showed enhanced yolk coloration and greater yolk total phenolic content. The T3 and T4 egg yolks showed lower MDA levels compared with T1, T2. Overall, results have shown that (a) xylanase inclusion affected egg yolk coloration and total phenolic content when combined with 2.5% PPB dietary supplementation; (b) dietary supplementation of 5% PPB resulted in eggs with reduced MDA levels. Full article

Moringa oleifera has been reported to possess a high number of bioactive compounds; hence, several food supplements are commercially available based on it. This work aimed to analyze the phytochemical composition and antioxidant activity of commercial food supplements. The phenolic composition of methanolic extracts was determined by using high-performance liquid chromatography with diode-array and electrospray ionization mass spectrometric detection (HPLC-DAD-ESI-MSⁿ), and the antioxidant activity was assessed by ABTS^·+ and DPPH assays. Thirty-three compounds were identified, and all the main compounds were quantified, observing that the main contribution to the phenolic profile was due to kaempferol and quercetin glucosides. The antioxidant activity in both assays agreed with the phenolic content: the higher the phenolic levels, the higher the antioxidant activity. The obtained results were compared with those previously published regarding Moringa oleifera leaves to establish the potential benefits of food supplement consumption in the diet. Full article

Infertility is an increasing global public health concern with socio-psychological implications for affected couples. Remarkable advances in reproductive medicine have led to successful treatments such as assisted reproductive techniques (ART). However, the search for new therapeutic tools to improve ART success rates has become a research hotspot. In the last few years, pineal indolamine melatonin has been investigated for its powerful antioxidant properties and its role in reproductive physiology. It is considered a promising therapeutical agent to counteract the detrimental effects associated with oxidative stress in fertility treatments. The aim of the present narrative review was to summarize the current state of the art on the importance of melatonin in reproductive physiology and to provide a critical evaluation of the data available encompassing basic, translational and clinical studies on its potential use in ART to improve fertility success rates. Full article

The present study was conducted to evaluate the effect of genipin (GEN) on the microglia of diabetic cognitive impairment and explore its potential mechanism. Diabetic mice were induced by STZ/HFD, while GEN was intragastrically and intraventricularly treated. The human microglia cell HMC3 was induced by LPS/HG/PA. As a result, GEN attenuated diabetic symptoms and diabetic cognitive impairment-related behavior in novel object recognition, Morris water maze and passive avoidance tests. GEN inhibited M1 microglia polarization, lipid accumulation, oxidative stress and promoted mitochondrial fusion via FABP4/Mfn1. FABP4 overexpression, Mfn1 overexpression, selective FABP4 inhibitor BMS, and Mfn1 SiRNA were employed for investigating the mechanism. The inhibitory effect of GEN on ROS may be associated with NOX2 signaling and the translocation of p47phox/p67phox to the cell membrane. With the ROS scavenger NAC, it was proved that ROS participated in GEN-mediated inflammation and lipid accumulation. GEN inhibited the phosphorylation and nucleus translocation of NF-κB. GEN inhibited the ubiquitination of Mfn1, which was mediated by the E3 ligase Hrd1. GEN also enhanced microglia phagocytosis. Molecular docking predicted that GEN may interact with FABP4 by hydrogen bond at the S53 and R78 residues. In conclusion, GEN attenuated diabetic cognitive impairment by inhibiting inflammation, lipid accumulation and promoting mitochondrial fusion via FABP4/Mfn1 signaling. Full article

This study examined whether diets with high dietary methionine levels could alleviate chronic heat stress in Chinese mitten crab Eriocheir sinensis. Crabs were fed three dietary methionine levels of 0.49%, 1.29% and 2.09% for six weeks. The analyzed methionine concentration of diets was 0.48%, 1.05% and 1.72%, respectively. Crabs were fed three different supplemental concentrations of dietary methionine at 24 °C and 30 °C, respectively. The trial was divided into six groups with five replicates in each group, and 40 juvenile crabs (initial average weight 0.71 ± 0.01 g) in each replicate. During the trial, crabs were fed twice daily (the diet of 4% of the body weight was delivered daily). The effects of dietary methionine level on nutrient metabolism, antioxidant capacity, apoptosis factors and immunity were evaluated at a normal water temperature of 24 °C and high temperature of 30 °C. Feed conversion ratio decreased under chronic heat stress. Chronic heat stress increased weight gain, specific growth rate, molting frequency, and protein efficiency ratio. The survival of crabs decreased under chronic heat stress, whereas a high level of dietary methionine significantly improved survival. Chronic heat stress induced lipid accumulation and protein content reduction. The high-methionine diet decreased lipid in the body and hepatopancreas, but increased protein in the body, muscle and hepatopancreas under chronic heat stress. Simultaneously, the high dietary methionine levels mitigated oxidative stress by reducing lipid peroxidation, restoring the antioxidant enzyme system, decreasing apoptosis and activating immune function under chronic heat stress. This study suggests that supplementing 1.72% dietary methionine could alleviate the adverse effects of a high water temperature in E. sinensis farming. Full article

To meet the demand for chicken meat production, new additives that promote growth and health without adverse effects on meat quality are being investigated. This study was conducted to investigate the effect of protected sodium butyrate (PSB) (0 vs. 2 g/kg), an olive leaf and grape-based by-product (OLG-mix), or a combined supplementation of PSB and OLG-mix on productive performance, antioxidant status, carcass, and meat quality in broilers. PSB improved performance parameters with greater effect in the initial phase. Both, PSB and OLG-mix increased the plasma superoxide dismutase (SOD); however, PSB supplementation was more effective to delay the lipid oxidation of meat from the initial day of storage. OLG-mix produced meat with greater color intensity, b* value and lesser drip losses than PSB. The combination of PSB + OLG-mix did not produce more marked effects that the individual administration; except to control the oxidation of meat. Linear and positive correlations between antioxidant enzymes and weight gain were observed. Significant linear and negative relationships were quantified between plasma SOD and meat lipid oxidation according to dietary treatment. Therefore, the present study would be a first approximation to the possibilities for predicting growth range and meat quality through the evaluation of the blood oxidative status. Full article

Clinical studies indicate that the consumption of soybean protein might reduce cholesterol and LDL levels preventing the development of atherosclerotic cardiovascular diseases. However, soybean variety can influence soybean protein profile and therefore affect soybean protein health-promoting properties. This study investigated the composition and effects of nineteen soybean varieties digested under simulated gastrointestinal conditions on hepatic cholesterol metabolism and LDL oxidation in vitro. Soybean varieties exhibited a differential protein hydrolysis during gastrointestinal digestion. Soybean varieties could be classified according to their composition (high/low glycinin:β-conglycinin ratio) and capacity to inhibit HMGCR (IC₅₀ from 59 to 229 µg protein mL⁻¹). According to multivariate analyses, five soybean varieties were selected. These soybean varieties produced different peptide profiles and differently reduced cholesterol concentration (43–55%) by inhibiting HMGCR in fatty-acid-stimulated HepG2 hepatocytes. Selected digested soybean varieties inhibited cholesterol esterification, triglyceride production, VLDL secretion, and LDL recycling by reducing ANGPTL3 and PCSK9 and synchronously increasing LDLR expression. In addition, selected soybean varieties hindered LDL oxidation, reducing the formation of lipid peroxidation early (conjugated dienes) and end products (malondialdehyde and 4-hydroxynonenal). The changes in HMGCR expression, cholesterol esterification, triglyceride accumulation, ANGPTL3 release, and malondialdehyde formation during LDL oxidation were significantly (p < 0.05) correlated with the glycinin:β-conglycinin ratio. Soybean varieties with lower glycinin:β-conglycinin exhibited a better potential in regulating cholesterol and LDL homeostasis in vitro. Consumption of soybean flour with a greater proportion of β-conglycinin may, consequently, improve the potential of the food ingredient to maintain healthy liver cholesterol homeostasis and cardiovascular function. Full article

Despite a relatively developed understanding of the pathophysiology underlying primary and secondary mechanisms of cell death after ischemic injury, there are few established treatments to improve stroke prognoses. A major contributor to secondary cell death is mitochondrial dysfunction. Recent advancements in cell-based therapies suggest that stem cells may be revolutionary for treating stroke, and the reestablishment of mitochondrial integrity may underlie these therapeutic benefits. In fact, functioning mitochondria are imperative for reducing oxidative damage and neuroinflammation following stroke and reperfusion injury. In this review, we will discuss the role of mitochondria in establishing the anti-oxidative effects of stem cell therapies for stroke. Full article

Objectives: Short-chain fatty acids (SCFAs), the main metabolites released from the gut microbiota, are altered during hypertension and obesity. SCFAs play a beneficial role in the cardiovascular system. However, the effect of SCFAs on cerebrovascular endothelial cells is yet to be uncovered. In this study, we use brain endothelial cells to investigate the in vitro effect of SCFAs on heme oxygenase 2 (HO-2) and mitochondrial function after angiotensin II (Ang-II) treatment. Methods: Brain human microvascular endothelial cells were treated with Ang-II (500 nM for 24 h) in the presence and absence of an SCFAs cocktail (1 μM; acetate, propionate, and butyrate) and/or HO-2 inhibitor (SnPP 5 μM). At the end of the treatment, HO-2, endothelial markers (p-eNOS and NO production), inflammatory markers (TNFα, NFκB-p50, and -p65), calcium homeostasis, mitochondrial membrane potential, mitochondrial ROS and H₂O₂, and mitochondrial respiration were determined in all groups of treated cells. Key Results: Our data showed that SCFAs rescued HO-2 after Ang-II treatment. Additionally, SCFAs rescued Ang-II-induced eNOS reduction and mitochondrial membrane potential impairment and mitochondrial respiration damage. On the other hand, SCFAs reduced Ang-II-induced inflammation, calcium dysregulation, mitochondrial ROS, and H₂O₂. All of the beneficial effects of SCFAs on endothelial cells and mitochondrial function occurred through HO-2. Conclusions: SCFAs treatment restored endothelial cells and mitochondrial function following Ang-II-induced oxidative stress. SCFAs exert these beneficial effects by acting on HO-2. Our results are opening the door for more studies to investigate the effect the of SCFAs/HO-2 axis on hypertension and obesity-induced cerebrovascular diseases. Full article

Type 2 diabetes reduces muscle mass and function. Chronic inflammation and mitochondrial dysfunction play critical roles in muscle atrophy pathogenesis. Here, we investigated the effects of bavachin and corylifol A from Psoralea corylifolia L. seeds on muscle atrophy in dexamethasone-treated mice and in db/db mice. Bavachin and corylifol A enhanced muscle strength and muscle mass in dexamethasone-treated mice. In diabetic mice, they enhanced muscle strength and cross-sectional areas. Bavachin and corylifol A suppressed inflammatory cytokine (interleukin-6 and tumor necrosis factor-α) expression levels by downregulating nuclear factor-κB phosphorylation. They decreased the muscle atrophic factor (myostatin, atrogin-1, and muscle RING finger-1) expression levels. They activated the AKT synthetic signaling pathway and induced a switch from fast-type glycolytic fibers (type 2B) to slow-type oxidative fibers (types I and 2A). They increased mitochondrial biogenesis and dynamic factor (optic atrophy-1, mitofusin-1/2, fission, mitochondrial 1, and dynamin 1-like) expression levels via the AMP-activated protein kinase–peroxisome proliferator-activated receptor gamma coactivator 1-alpha signaling pathway. They also improved mitochondrial quality by upregulating the mitophagy factor (p62, parkin, PTEN-induced kinase-1, and BCL2-interacting protein-3) expression levels. Therefore, bavachin and corylifol A exert potential therapeutic effects on muscle atrophy by suppressing inflammation and improving mitochondrial function. Full article

Retinitis pigmentosa (RP) is the most common inherited retinal dystrophy causing progressive vision loss. It is accompanied by chronic and sustained inflammation, including M1 microglia activation. This study evaluated the effect of an essential fatty acid (EFA) supplement containing specialized pro-resolving mediators (SPMs), on retinal degeneration and microglia activation in rd10 mice, a model of RP, as well as on LPS-stimulated BV2 cells. The EFA supplement was orally administered to mice from postnatal day (P)9 to P18. At P18, the electrical activity of the retina was examined by electroretinography (ERG) and innate behavior in response to light were measured. Retinal degeneration was studied via histology including the TUNEL assay and microglia immunolabeling. Microglia polarization (M1/M2) was assessed by flow cytometry, qPCR, ELISA and histology. Redox status was analyzed by measuring antioxidant enzymes and markers of oxidative damage. Interestingly, the EFA supplement ameliorated retinal dysfunction and degeneration by improving ERG recording and sensitivity to light, and reducing photoreceptor cell loss. The EFA supplement reduced inflammation and microglia activation attenuating M1 markers as well as inducing a shift to the M2 phenotype in rd10 mouse retinas and LPS-stimulated BV2 cells. It also reduced oxidative stress markers of lipid peroxidation and carbonylation. These findings could open up new therapeutic opportunities based on resolving inflammation with oral supplementation with SPMs such as the EFA supplement. Full article

Bromelain, a cysteine protease found in pineapple, has beneficial effects in the treatment of inflammatory diseases; however, its effects in cardiovascular pathophysiology are not fully understood. We investigated the effect of bromelain on atherosclerosis and its regulatory mechanisms in hyperlipidemia and atheroprone apolipoprotein E-null (apoe^−/−) mice. Bromelain was orally administered to 16-week-old male apoe^−/− mice for four weeks. Daily bromelain administration decreased hyperlipidemia and aortic inflammation, leading to atherosclerosis retardation in apoe^−/− mice. Moreover, hepatic lipid accumulation was decreased by the promotion of cholesteryl ester hydrolysis and autophagy through the AMP-activated protein kinase (AMPK)/transcription factor EB (TFEB)-mediated upregulation of autophagy- and antioxidant-related proteins. Moreover, bromelain decreased oxidative stress by increasing the antioxidant capacity and protein expression of antioxidant proteins while downregulating the protein expression of NADPH oxidases and decreasing the production of reactive oxygen species. Therefore, AMPK/TFEB signaling may be crucial in bromelain-mediated anti-hyperlipidemia, antioxidant, and anti-inflammatory effects, effecting the amelioration of atherosclerosis. Full article

The term “cytokine storm” describes an acute pathophysiologic state of the immune system characterized by a burst of cytokine release, systemic inflammatory response, and multiple organ failure, which are crucial determinants of many disease outcomes. In light of the complexity of cytokine storms, specific strategies are needed to prevent and alleviate their occurrence and deterioration. Nuclear factor erythroid 2-related factor 2 (NRF2) is a CNC-basic region-leucine zipper protein that serves as a master transcription factor in maintaining cellular redox homeostasis by orchestrating the expression of many antioxidant and phase II detoxification enzymes. Given that inflammatory response is intertwined with oxidative stress, it is reasonable to assume that NRF2 activation limits inflammation and thus cytokine storms. As NRF2 can mitigate inflammation at many levels, it has emerged as a potential target to prevent and treat cytokine storms. In this review, we summarized the cytokine storms caused by different etiologies and the rationale of interventions, focusing mainly on NRF2 as a potential therapeutic target. Full article

Nowadays, oxidative cell damage is one of the common features of cancer and Alzheimer’s disease (AD), and Se-containing molecules, such as ebselen, which has demonstrated strong antioxidant activity, have demonstrated well-established preventive effects against both diseases. In this study, a total of 39 Se-derivatives were synthesized, purified, and spectroscopically characterized by NMR. Antioxidant ability was tested using the DPPH assay, while antiproliferative activity was screened in breast, lung, prostate, and colorectal cancer cell lines. In addition, as a first approach to evaluate their potential anti-Alzheimer activity, the in vitro acetylcholinesterase inhibition (AChEI) was tested. Regarding antioxidant properties, compound 13a showed concentration- and time-dependent radical scavenging activity. Additionally, compounds 14a and 17a showed high activity in the melanoma and ovarian cancer cell lines, with LD₅₀ values below 9.2 µM. Interestingly, in the AChEI test, compound 14a showed almost identical inhibitory activity to galantamine along with a 3-fold higher in vitro BBB permeation (Pe = 36.92 × 10⁻⁶ cm/s). Molecular dynamics simulations of the aspirin derivatives (14a and 14b) confirm the importance of the allylic group instead of the propargyl one. Altogether, it is concluded that some of these newly synthesized Se-derivatives, such as 14a, might become very promising candidates to treat both cancer and AD. Full article

Obesity has emerged as a major public health concern with a staggering 39% worldwide prevalence as of 2021. Given the magnitude of the problem and considering its association with chronic low-grade systemic inflammation, it does not come as a surprise that obesity is now considered one of the major risk factors for the development of several chronic diseases, such as diabetes, cardiovascular problems, and cancer. Adipose tissue dysfunction in obesity has taken center stage in understanding how changes in its components, particularly adipocytes and macrophages, participate in such processes. In this review, we will initially focus on how changes in adipose tissue upon excess fat accumulation generate endocrine signals that promote cancer development. Moreover, the tumor microenvironment or stroma, which is also critical in cancer development, contains macrophages and adipocytes, which, in reciprocal paracrine communication with cancer cells, generate relevant signals. We will discuss how paracrine signaling in the tumor microenvironment between cancer cells, macrophages, and adipocytes favors cancer development and progression. Finally, as reactive oxygen species participate in many of these signaling pathways, we will summarize the information available on how antioxidants can limit the effects of endocrine and paracrine signaling due to dysfunctional adipose tissue components in obesity. Full article