Antioxidants, Volume 12, Issue 12 (December 2023) – 114 articles

Portulaca oleracea L. (purslane) is a food and a traditional drug worldwide. It exhibits anti-inflammatory, anti-oxidative, anti-tumor, and anti-diabetic bioactivities; but its activity on diabetic-associated endothelial dysfunction is unknown. This study aimed to investigate the effect of purslane on endothelial function and the underlying mechanisms. Male C57BL/6 mice had 14-week ad libitum access to a high-fat rodent diet containing 60% kcal% fat to induce obesity and diabetes whereas purslane extract (200 mg/kg/day) was administered during the last 4 weeks via intragastric gavage. Primary rat aortic endothelial cells and isolated mouse aortas were cultured with a risk factor, high glucose or tunicamycin, together with purslane extract. By ESI-QTOF-MS/MS, flavonoids and their glycoside products were identified in the purslane extract. Exposure to high glucose or tunicamycin impaired acetylcholine-induced endothelium-dependent relaxations in aortas and induced endoplasmic reticulum (ER) stress and oxidative stress with the downregulation of 5′ AMP-activated protein kinase (AMPK)/ endothelial nitric oxide synthase (eNOS) signaling. Co-incubation with purslane significantly ameliorated these impairments. The effects of purslane were abolished by Compound C (AMPK inhibitor). Four-week purslane treatment ameliorated aortic relaxations, ER stress, and oxidative stress in diabetic obese mice. This study supported that purslane protected endothelial function, and inhibited ER stress and oxidative stress in vasculature through AMPK/eNOS activation, revealing its therapeutic potential against vascular complications in diabetes. Full article

Immunotherapies, particularly those concerning immune checkpoint inhibitors, have transformed cancer treatment in recent years. Programmed death-ligand 1 (PD-L1) is a key target for immunotherapy that is overexpressed in the cells of colorectal cancer, a widespread malignant cancer that poses a significant healthcare challenge. This study investigated the effects of cosmosiin treatment on colorectal cancer cell lines. Cosmosiin is a naturally occurring flavone glycoside compound that has potential health benefits, including antioxidant and immunomodulatory effects. This study showed that cosmosiin effectively suppresses the expression of PD-L1 and triggers apoptosis, which is facilitated through pathways that are related to reactive oxygen species. These outcomes suggest that cosmosiin could be a promising candidate for an immune checkpoint inhibitor in the treatment of colorectal cancer. Full article

Yogurt acid whey (YAW) is a by-product of Greek strained yogurt production. The disposal of YAW constitutes an environmental problem, and given the increasing demand of Greek yogurt worldwide, its handling is a challenge. However, whey-derived peptides, resulting from microbial fermentation as well as those resulting from further hydrolysis during the digestion process, have been linked to enhanced biological activities. In this study, the antioxidant capacity of 33 samples of YAW obtained from Greek dairy companies of bovine, ovine or caprine origin was investigated using both cell-free and cell-based assays. The YAW samples, their in vitro digestion products (YAW-Ds) and a fraction of the digests (less than 3 kDa; YAW-D-P3) were assessed using four biochemical assays, namely ORAC, ABTS, FRAP and P-FRAP. Our data revealed a higher antioxidant capacity for digested samples compared with undigested samples, with all four methods. ORAC values after in vitro digestion were higher for the ovine samples compared to their bovine (YAW-D and YAW-D-P3) and caprine (YAW-D-P3) counterparts. Furthermore, the YAW-D-P3 fraction derived from samples collected in the summer months exhibited higher ORAC values when compared to the respective fraction from the winter months’ samples. The cellular antioxidant activity of ovine YAW-D-P3 was improved in H₂O₂-treated HT29 cells compared to the control H₂O₂-treated cells. However, YAW-D-P3 could not trigger either the pathways involving the transcription factors NF-κB or NFE2L2 or the gene expression of SOD1, CAT and HMOX1 in LPS-challenged THP-1-derived macrophages. These results suggest that YAW, and particularly YAW from ovine origin, could be used as a natural source for its antioxidant potential in human and animal nutrition. Full article

Chronic oxidative stress impairs the normal functioning of the retinal pigment epithelium (RPE), leading to atrophy of this cell layer in cases of advance age-related macular degeneration (AMD). The purpose of our study was to determine if buspirone, a partial serotonin 1A (5-HT1A) receptor agonist, protected against oxidative stress-induced changes in the RPE. We exposed differentiated human ARPE-19 cells to paraquat to induce oxidative damage in culture, and utilized a mouse model with sodium iodate (NaIO₃)-induced oxidative injury to evaluate the effect of buspirone. To investigate buspirone’s effect on protective gene expression, we performed RT–PCR. Cellular toxicities and junctional abnormalities due to paraquat induction in ARPE-19 cells and buspirone’s impact were assessed via WST-1 assays and ZO-1 immunostaining. We used spectral-domain optical coherence tomography (SD-OCT) and ZO-1 immunostaining of RPE/choroid for structural analysis. WST-1 assays showed dose-dependent protection of viability in buspirone-treated ARPE-19 cells in culture and preservation of RPE junctional integrity under oxidative stress conditions. In the NaIO₃ model, daily intraperitoneal injection (i.p.) of buspirone (30 mg/kg) for 12 days improved the survival of photoreceptors compared to those of vehicle-treated eyes. ZO-1-stained RPE flat-mounts revealed the structural preservation of RPE from oxidative damage in buspirone-treated mice, as well as in buspirone-induced Nqo1, Cat, Sqstm1, Gstm1, and Sod2 genes in the RPE/choroid compared to untreated eyes. Since oxidative stress is implicated in the pathogenesis AMD, repurposing buspirone, which is currently approved for the treatment of anxiety, might be useful in treating or preventing dry AMD. Full article

A 10-week growth experiment was conducted to assess the physiological response of spotted seabass (Lateolabrax maculatus) raised at moderate (27 °C) and high temperatures (33 °C) to different dietary available phosphorus (P) levels. Five diets with available P levels of 0.35, 0.55, 0.71, 0.82 and 0.92% were formulated, respectively. A water temperature of 33 °C significantly decreased growth performance and feed utilization, and increased oxidative stress and lipid deposition of spotted seabass compared with 27 °C. A second-order polynomial regression analysis based on weight gain (WG) showed that the available P requirement of spotted seabass raised at 27 °C and 33 °C was 0.72% and 0.78%, respectively. The addition of 0.71–0.82% P to the diet improved the growth performance, feed utilization, and antioxidant capacity of spotted seabass and alleviated the excessive lipid deposition compared with the low-P diet (0.35% P). Moreover, the addition of 0.71–0.92% P to diets increased the diversity of intestinal microbiota and the relative abundance of Lactococcus lactis and decreased the relative abundance of Plesiomonas compared with the low-P diet. Thus, dietary supplementation with 0.71–0.82% P improved the growth performance, antioxidant capacity and microbial composition of spotted seabass, and alleviated the disturbance of lipid metabolism caused by high temperature or low-P diet. Full article

The aims of the present study were to evaluate for the first time the chemical composition and antioxidant, antibacterial, antifungal and antiproliferative potentials of the Romanian George 90 lavender species, as well as parental species, L. angustifolia and L. latifolia. The L. angustifolia, L. latifolia and George 90 essential oils were analyzed by GC-MS/MS and the L. angustifolia, L. latifolia and George 90 hydroalcoholic extracts were analyzed by HPLC-DAD. The antioxidant, antibacterial, antifungal and antiproliferative assays revealed that all the investigated species showed significant activities. The results highlighted the chemical composition and the promising biological potentials of the L. angustifolia, L. latifolia and George 90 lavender species, validating their ethnomedicinal value, which offers potential applications as natural drugs. Full article

Stroke represents one of the main causes of death and disability in the world; despite this, pharmacological therapies against stroke remain insufficient. Ischemic stroke is the leading etiology of stroke. Different molecular mechanisms, such as excitotoxicity, oxidative stress, and inflammation, participate in cell death and tissue damage. At a preclinical level, different garlic compounds have been evaluated against these mechanisms. Additionally, there is evidence supporting the participation of garlic compounds in other mechanisms that contribute to brain tissue recovery, such as neuroplasticity. After ischemia, neuroplasticity is activated to recover cognitive and motor function. Some garlic-derived compounds and preparations have shown the ability to promote neuroplasticity under physiological conditions and, more importantly, in cerebral damage models. This work describes damage/repair mechanisms and the importance of garlic as a source of antioxidant and anti-inflammatory agents against damage. Moreover, we examine the less-explored neurotrophic properties of garlic, culminating in proposals and observations based on our review of the available information. The aim of the present study is to propose that garlic compounds and preparations could contribute to the treatment of ischemic stroke through their neurotrophic effects. Full article

The goal of this research was nutritional evaluation through the phytochemical analysis of blackberry and raspberry leaves, the screening of their biological activity (antioxidant capacity and inhibition of lipid peroxidation), and the investigation of the effect of in vitro gastrointestinal digestion (GID) of blackberry and raspberry leaves on the bioaccessibility of polyphenol subclasses. The concentrations of the analyzed liposoluble antioxidants were higher (p < 0.05) in blackberry leaves compared to raspberry leaves, while a significant (p < 0.05) higher content of water-soluble antioxidants was registered in raspberry leaves (with a total polyphenol content of 26.2 mg GAE/g DW of which flavonoids accounted for 10.6 mg/g DW). Blackberry leaves had the highest antioxidant capacity inhibition of the superoxide radicals (O₂^•−), while raspberry leaves registered the highest inhibition of hydroxyl radicals (^•OH), suggesting a high biological potency in scavenging-free radicals under in vitro systems. The maximum inhibition percentage of lipid peroxidation was obtained for blackberry leaves (24.86% compared to 4.37% in raspberry leaves), suggesting its potential to limit oxidative reactions. Simulated in vitro digestion showed that hydroxybenzoic acids registered the highest bioaccessibility index in the intestinal phase of both types of leaves, with gallic acid being one of the most bioaccessible phenolics. The outcomes of this investigation reveal that the most significant release of phenolic compounds from blackberry and raspberry leaves occurs either during or after the gastric phase. Knowledge about the bioaccessibility and stability of polyphenol compounds during digestion can provide significant insights into the bioavailability of these molecules and the possible effectiveness of plant metabolites for human health. Full article

Anesthesia serves as an effective method to mitigate the stress response in aquatic animals during aquaculture and product transportation. In this study, we assessed the anesthetic efficacy of clove oil, tricaine methane-sulfonate (MS-222), ethanol, and magnesium chloride by anesthesia duration, recovery time, 24-hour survival rate, and the behavior of mud crabs (Scylla paramamosain). Additionally, the optimal anesthetic concentration for varying body weights of mud crabs was also investigated. The results revealed that clove oil emerged as the optimal anesthetic for mud crabs, with a 24-hour survival rate surpassing those observed in MS-222 and magnesium chloride treatments. Ethanol caused amputation and hyperactivity in mud crabs. Regression analyses between the optimal anesthetic concentration of clove oil and the weight categories of 0.03–27.50 g and 27.50–399.73 g for mud crabs yielded the following equations: y = 0.0036 x³ − 0.1629 x² + 1.7314 x + 4.085 (R² = 0.7115) and y = 0.0437 x + 2.9461 (R² = 0.9549). Clove oil exhibited no significant impact on serum cortisol, glucose, lactate content, aspartate aminotransferase (AST), alanine aminotransferase (ALT) activities, or superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels in mud crabs across different treatment groups. Anesthesia induced by clove oil in mud crabs resulted in an increase in inhibitory neurotransmitters such as glycine. However, the recovery from anesthesia was associated with elevated levels of the excitatory neurotransmitters L-aspartic acid and glutamate. In conclusion, clove oil proves to be a safe and optimal anesthetic agent for mud crabs, exerting no physiological stress on the species. Full article

After parturition, bovine endometrial epithelial cells (BEECs) undergo serious inflammation and imbalance between oxidation and antioxidation, which is widely acknowledged as a primary contributor to the development of endometritis in dairy cows. Nevertheless, the mechanism of oxidative stress-mediated inflammation and damage in bovine endometrial epithelial cells remains inadequately defined, particularly the molecular pathways associated with mitochondria-dependent apoptosis. Hence, the present study was designed to explore the mechanism responsible for mitochondrial dysfunction-induced BEEC damage. In vivo, the expressions of proapoptotic protein caspase 3 and cytochrome C were increased significantly in dairy uteri with endometritis. Similarly, the levels of proapoptotic protein caspase 3, BAX, and cytochrome C were markedly increased in H₂O₂-treated BEECs. Our findings revealed pronounced BEEC damage in dairy cows with endometritis, accompanied by heightened expression of cyto-C and caspase-3 both in vivo and in vitro. The reduction in apoptosis-related protein of BEECs due to oxidant injury was notably mitigated following N-acetyl-L-cysteine (NAC) treatment. Furthermore, mitochondrial vacuolation was significantly alleviated, and mitochondrial membrane potential returned to normal levels after the removal of ROS. Excessive ROS may be the main cause of mitochondrial dysfunction. Mitochondrial permeability transition pore (mPTP) blockade by cyclophilin D (CypD) knockdown with CSA significantly blocked the flow of cytochrome C (cyto-C) and Ca²⁺ to the cytoplasm from the mitochondria. Our results indicate that elevated ROS and persistent opening of the mPTP are the main causes of oxidative damage in BEECs. Collectively our results reveal a new mechanism involving ROS-mPTP signaling in oxidative damage to BEECs, which may be a potential avenue for the clinical treatment of bovine endometritis. Full article

Exposure to traffic-related air pollution (TRAP) generates oxidative stress, with downstream effects at the metabolic level. Human studies of traffic density and metabolomic markers, however, are rare. The main objective of this study was to evaluate the cross-sectional association between traffic density in the street of residence with oxidative stress and metabolomic profiles measured in a population-based sample from Spain. We also explored in silico the potential biological implications of the findings. Secondarily, we assessed the contribution of oxidative stress to the association between exposure to traffic density and variation in plasma metabolite levels. Traffic density was defined as the average daily traffic volume over an entire year within a buffer of 50 m around the participants’ residence. Plasma metabolomic profiles and urine oxidative stress biomarkers were measured in samples from 1181 Hortega Study participants by nuclear magnetic resonance spectroscopy and high-performance liquid chromatography, respectively. Traffic density was associated with 7 (out of 49) plasma metabolites, including amino acids, fatty acids, products of bacterial and energy metabolism and fluid balance metabolites. Regarding urine oxidative stress biomarkers, traffic associations were positive for GSSG/GSH% and negative for MDA. A total of 12 KEGG pathways were linked to traffic-related metabolites. In a protein network from genes included in over-represented pathways and 63 redox-related candidate genes, we observed relevant proteins from the glutathione cycle. GSSG/GSH% and MDA accounted for 14.6% and 12.2% of changes in isobutyrate and the CH₂CH₂CO fatty acid moiety, respectively, which is attributable to traffic exposure. At the population level, exposure to traffic density was associated with specific urine oxidative stress and plasma metabolites. Although our results support a role of oxidative stress as a biological intermediary of traffic-related metabolic alterations, with potential implications for the co-bacterial and lipid metabolism, additional mechanistic and prospective studies are needed to confirm our findings. Full article

Commercially available tea extracts for dietary supplements and nutraceuticals are standardized to characteristic components of Camellia sinensis L., such as epigallocatechin gallate (EGCG) and total catechins or polyphenols. However, since most commercial tea extracts are highly concentrated into only one molecule such as EGCG, the comparatively less stable catechin, the oxidative stability of the extract during the 24-month shelf life was questioned. It was hypothesized that the overall oxidative stability is reduced for highly purified/concentrated tea extracts due to the absence of other natural antioxidants stabilizing the complex mixture. Via liquid chromatographic analysis, the individual chromatographic profiles of 30 commercial white, green, and black tea extracts were evaluated and compared regarding oxidative stability and functional properties. The contents of bioactive flavan-3-ols, theaflavins, and methylxanthines differed much from what was claimed by the suppliers. At the end of the product shelf life, most of the commercial green and black tea extracts showed a decrease in the flavan-3-ol content, the main bioactive components of tea. A high EGCG content to the detriment of other possibly stabilizing flavan-3-ols or antioxidants in tea was found to explain the lower oxidative stability of such tea extract products. A natural overall composition of molecular structures was found to be superior to a strong enrichment in just one molecule. Full article

Verticillium wilt of olive (VWO) is one of the most widespread and devastating olive diseases in the world. Harnessing host resistance to the causative agent is considered one of the most important measures within an integrated control strategy of the disease. Aiming to understand the mechanisms underlying olive resistance to VWO, the metabolic profiles of olive leaves, stems and roots from 10 different cultivars with varying levels of susceptibility to this disease were investigated by liquid chromatography coupled to mass spectrometry (LC-MS). The distribution of 56 metabolites among the three olive tissues was quantitatively assessed and the possible relationship between the tissues’ metabolic profiles and resistance to VWO was evaluated by applying unsupervised and supervised multivariate analysis. Principal component analysis (PCA) was used to explore the data, and separate clustering of highly resistant and extremely susceptible cultivars was observed. Moreover, partial least squares discriminant analysis (PLS-DA) models were built to differentiate samples of highly resistant, intermediate susceptible/resistant, and extremely susceptible cultivars. Root models showed the lowest classification capability, but metabolites from leaf and stem were able to satisfactorily discriminate samples according to the level of susceptibility. Some typical compositional patterns of highly resistant and extremely susceptible cultivars were described, and some potential resistance/susceptibility metabolic markers were pointed out. Full article

Ferroptosis is involved in various tissue injuries including neurodegeneration, ischemia-reperfusion injury, and acute liver injury. Ferroptosis inhibitors exhibit promising clinical potential in the treatment of various diseases. As a traditional chemical, silymarin has been widely used in healthcare and clinical applications to treat liver injuries in which ferroptosis is involved. Silibinin is the main active ingredient of silymarin. However, the effect of silibinin on ferroptosis and ferroptosis-related diseases remains unclear. Here, we found that silibinin inhibited death in different kinds of cells caused by ferroptosis inducers including RSL3 and erastin. Moreover, silibinin alleviated lipid peroxidation induced by RSL3 without affecting the labile iron pool. Next, the antioxidant activity of silibinin was demonstrated by the DPPH assay. In vivo, silibinin strikingly relieved tissue injuries and ferroptosis in the liver and kidney of glutathione peroxidase 4 (GPX4) knockout C57 BL/6J mice. Moreover, silibinin effectively rescued renal ischemia-reperfusion, a well-known ferroptosis-related disease. In conclusion, our study revealed that silibinin effectively inhibits cell ferroptosis and ferroptosis-related tissue injuries, implicating silibinin as a potential chemical to treat ferroptosis-related diseases. Full article

Methotrexate (MTX) therapy encounters significant limitations due to the significant concern of drug-induced liver injury (DILI), which poses a significant challenge to its usage. To mitigate the deleterious effects of MTX on hepatic function, researchers have explored plant sources to discover potential hepatoprotective agents. This study investigated the hepatoprotective effects of the ethanolic extract derived from the aerial parts of Chamaecyparis lawsoniana (CLAE) against DILI, specifically focusing on MTX-induced hepatotoxicity. UPLC-ESI-MS/MS was used to identify 61 compounds in CLAE, with 31 potential bioactive compounds determined through pharmacokinetic analysis. Network pharmacology analysis revealed 195 potential DILI targets for the bioactive compounds, including TP53, IL6, TNF, HSP90AA1, EGFR, IL1B, BCL2, and CASP3 as top targets. In vivo experiments conducted on rats with acute MTX-hepatotoxicity revealed that administering CLAE orally at 200 and 400 mg/kg/day for ten days dose-dependently improved liver function, attenuated hepatic oxidative stress, inflammation, and apoptosis, and reversed the disarrayed hepatic histological features induced by MTX. In general, the findings of the present study provide evidence in favor of the hepatoprotective capabilities of CLAE in DILI, thereby justifying the need for additional preclinical and clinical investigations. Full article

Oocyte quality is a pivotal determinant of assisted reproductive outcomes. The quality of oocytes is intricately linked to their developmental microenvironment, particularly the levels of oxidative stress within the follicular fluid. Oxidative stress levels in follicular fluid may have a substantial influence on oocyte health, thereby impacting the outcomes of ART procedures. This review meticulously explores the intricate relationship between oxidative stress in follicular fluid and ART outcomes. Furthermore, it delves into strategies aimed at ameliorating the oxidative stress status of follicular fluid, with the overarching goal of enhancing the overall efficacy of ART. This research endeavors to establish a robust foundation and provide valuable guidance for clinical treatment approaches, particularly in the context of infertile women, including those of advanced maternal age. Full article

The antioxidant and anti-inflammatory abilities of beeswax alcohol (BWA) are well reported in animal and human clinical studies, with a significant decrease in malondialdehyde (MDA) in the blood, reduced liver steatosis, and decreased insulin. However, there has been insufficient information to explain BWAs in vitro antioxidant and anti-inflammatory activity owing to its limited solubility in an aqueous buffer system. Herein, three distinct reconstituted high-density lipoproteins (rHDL) were prepared with palmitoyloleoyl phosphatidylcholine (POPC), cholesterol, apolipoprotein A-I (apoA-I), and BWA at molar ratios of 95:5:1:0 (rHDL-0), 95:5:1:0.5 (rHDL-0.5), and 95:5:1:1 (rHDL-1) and examined for antioxidant and anti-glycation effects. A rHDL containing BWA, precisely rHDL-1, displayed a remarkable anti-glycation effect against fructose (final 250 mM), induced glycation of HDL, and prevented proteolytic degradation of apoA-I. Also, BWA incorporated rHDL-0.5, and rHDL-1 displayed substantial antioxidant activity by inhibiting cupric ion-mediated low-density lipoprotein (LDL) oxidation. In contrast to rHDL-0, a 20 and 22% enhancement in ferric ion reduction ability (FRA) and paraoxonase (PON) activity was observed in HDL treated with rHDL-1, signifying the effect of BWA on the antioxidant activity enhancement of HDL. rHDL-1 efficiently inhibits N^ε-carboxylmethyllysine (CML)-induced reactive oxygen species (ROS) generation and apoptosis in zebrafish embryos, consequently improving embryo survivability and developmental deformities impaired by the CML. The dermal application of rHDL-1 to the CML-impaired cutaneous wound of the adult zebrafish inhibited ROS production and displayed potent wound-healing activity. Conclusively, incorporating BWA in rHDL significantly enhanced the anti-glycation and antioxidant activities in rHDL via more stabilization of apoA-I with a larger particle size. The rHDL containing BWA facilitated the inherent antioxidant ability of HDL to suppress the CML-induced toxicities in zebrafish embryos and ameliorate CML-aggravated chronic wounds in adult zebrafish. Full article

Broccoli by-products are an important source of health-promoting bioactive compounds, although they are generally underutilized. This study aimed to valorize non-compliant broccoli florets by transforming them into functional ingredients for biscuit formulation. A broccoli flour and three water/ethanol extracts (100:0, 75:25, 50:50; v/v) were obtained. The rheological properties and the content of bioactive compounds of the functional ingredients and biscuits were evaluated. The 50:50 hydroalcoholic extract was the richest in glucosinolates (9749 µg·g⁻¹ DW); however, the addition of a small amount strongly affected dough workability. The enrichment with 10% broccoli flour resulted the best formulation in terms of workability and color compared to the other enriched biscuits. The food matrix also contributed to protecting bioactive compounds from thermal degradation, leading to the highest total glucosinolate (33 µg·g⁻¹ DW), carotenoid (46 µg·g⁻¹ DW), and phenol (1.9 mg GAE·g⁻¹ DW) contents being present in the final biscuit. Therefore, broccoli flour is a promising ingredient for innovative healthy bakery goods. Hydroalcoholic extracts could be valuable ingredients for liquid or semi-solid food formulation. Full article

Background: The Mediterranean diet is linked to various health benefits, especially the consumption of olive oil as a key component. Multiple studies highlight its advantages, particularly due to its fatty acid composition and additional components like phenolic compounds. A significant antioxidant compound, oleocanthal, known for its antioxidant properties, has gained attention in the pharmaceutical industry for its anti-inflammatory and antiproliferative effects. It shows promise in addressing cardiovascular diseases, metabolic syndrome, and neuroprotection. This systematic review aims to evaluate the existing literature on oleocanthal, examining its role in biological processes and potential impact on conditions like inflammation and cancer. Methods: We performed several searches in PubMed (MEDLINE), Web of Science (WOS), and Cochrane based on the terms “Oleocanthal”, “Cancer”, and “Inflammation”. The inclusion criteria were as follows: studies whose main topics were oleocanthal and cancer or inflammation. On the other hand, the exclusion criteria were studies that were not focused on oleocanthal, reviews, or editorial material. Given that these findings are explanatory rather than derived from clinical trials, we refrained from employing methods to assess potential bias. This systematic review did not receive any external funding. Results: We found 174 records from these searches, where we discarded reviews and editorial material, duplicated articles, and 1 retracted article. Finally, we had 53 reports assessed for eligibility that were included in this review. Discussion: OC exhibits promising therapeutic potential against both inflammation and cancer. We addressed its ability to target inflammatory genes and pathways, offering potential treatments for conditions like rheumatic diseases by regulating pathways such as NF-kB and MAPK. Additionally, OC’s anticancer properties, particularly its notable inhibition of c-Met signaling across various cancers, highlight its efficacy, showcasing promise as a potential treatment. Full article

Lipofuscin accumulates with age as intracellular fluorescent granules originating from incomplete lysosomal digestion of phagocytosed and autophagocytosed material. The purpose of this review is to provide an update on the current understanding of the role of oxidative stress and/or lysosomal dysfunction in lipofuscin accumulation and its consequences, particularly for retinal pigment epithelium (RPE). Next, the fluorescence of lipofuscin, spectral changes induced by oxidation, and its contribution to retinal fluorescence are discussed. This is followed by reviewing recent developments in fluorescence imaging of the retina and the current evidence on the prognostic value of retinal fluorescence for the progression of age-related macular degeneration (AMD), the major blinding disease affecting elderly people in developed countries. The evidence of lipofuscin oxidation in vivo and the evidence of increased oxidative damage in AMD retina ex vivo lead to the conclusion that imaging of spectral characteristics of lipofuscin fluorescence may serve as a useful biomarker of oxidative damage, which can be helpful in assessing the efficacy of potential antioxidant therapies in retinal degenerations associated with accumulation of lipofuscin and increased oxidative stress. Finally, amendments to currently used fluorescence imaging instruments are suggested to be more sensitive and specific for imaging spectral characteristics of lipofuscin fluorescence. Full article

Alzheimer’s disease (AD) is known as the primary and most common cause of dementia in the middle-aged and elderly population worldwide. Chemical analyses of B. pendula leaf extract (BPE), performed using spectrophotometric and chromatographic methods (LC/MS), revealed high amounts of polyphenol carboxylic acids (gallic, chlorogenic, caffeic, trans-p-coumaric, ferulic, and salicylic acids), as well as flavonoids (apigenin, luteolin, luteolin-7-O-glucoside, naringenin, hyperoside, quercetin, and quercitrin). Four groups of Wistar rats were used in this experiment (n = 7/group): control (untreated), Aβ_1-42 (2 μg/rat intracerebroventricular (i.c.v.), Aβ_1-42 + BPE (200 mg/Kg b.w.), and DMSO (10 μL/rat). On the first day, one dose of Aβ_1-42 was intracerebroventricularly administered to animals in groups 2 and 3. Subsequently, BPE was orally administered for the next 15 days to group 3. On the 16th day, behavioral tests were performed. Biomarkers of brain oxidative stress Malondialdehyde (MDA), (Peroxidase (PRx), Catalase (CAT), and Superoxid dismutase (SOD) and inflammation (cytokines: tumor necrosis factor -α (TNF-α), Interleukin 1β (IL-1β), and cyclooxygenase-2 (COX 2)) in plasma and hippocampus homogenates were assessed. Various protein expressions (Phospho-Tau (Ser404) (pTau Ser 404), Phospho-Tau (Ser396) (pTau Ser 396), synaptophysin, and the Nuclear factor kappa B (NFkB) signaling pathway) were analyzed using Western blot and immunohistochemistry in the hippocampus. The results show that BPE diminished lipid peroxidation and neuroinflammation, modulated specific protein expression, enhanced the antioxidant capacity, and improved spontaneous alternation behavior, suggesting that it has beneficial effects in AD. Full article

Cervical cancer is a prevalent and often devastating disease affecting women worldwide. Traditional treatment modalities such as surgery, chemotherapy, and radiation therapy have significantly improved survival rates, but they are often accompanied by side effects and challenges that can impact a patient’s quality of life. In recent years, the integration of essential oils into the management of cervical cancer has gained attention. This review provides an in-depth exploration of the role of various essential oils in cervical cancer, offering insights into their potential benefits and the existing body of research. The review also delves into future directions and challenges in this emerging field, emphasizing promising research areas and advanced delivery systems. The encapsulation of essential oils with solid lipid nanoparticles, nanoemulsification of essential oils, or the combination of essential oils with conventional treatments showed promising results by increasing the anticancer properties of essential oils. As the use of essential oils in cervical cancer treatment or management evolves, this review aims to provide a comprehensive perspective, balancing the potential of these natural remedies with the challenges and considerations that need to be addressed. Full article

The zucchini (Cucurbita pepo L.) plant is well known for its fruits; however, its edible flowers appear to contain several active molecules, including polyphenols, which display poor bioaccessibility after gastrointestinal digestion (GiD). This study explores the bioaccessibility of polyphenols and antioxidant capacity within zucchini flower extracts during simulated GiD. Two nutraceutical formulations, non-acid-resistant (NAcR) and acid-resistant (AcR) capsules containing an aqueous extract of zucchini flowers, were employed in this investigation. Additionally, high-resolution mass spectrometry (Q-Orbitrap HRMS) was utilized for a comprehensive analysis of their polyphenolic constituents. Predominantly, rutin and isorhamnetin-3-rutinoside were the most prevalent compounds detected in the samples (514.62 and 318.59 mg/kg, respectively). Following in vitro GiD, the extract encapsulated in AcR capsules exhibited enhanced bioaccessibility during both the duodenal (189.2 and 162.5 mg GAE/100 g, respectively) and colonic stages (477.4 and 344.7 mg GAE/100 g, respectively) when compared with the extract encapsulated in NAcR capsules. This suggests that gastric acidity adversely impacted the release of polyphenols from NAcR capsules. In conclusion, the aqueous zucchini flower extract emerges as a promising and readily accessible source of dietary polyphenols. Moreover, the utilization of AcR capsules presents a potential nutraceutical formulation strategy to improve polyphenol bioaccessibility, enhancing its applicability in promoting health and well-being. Full article

Life expectancy has increased globally in recent decades, driving interest in maintaining a healthy life that includes preservation of physical and mental abilities, particularly in elderly people. The gut microbiome becomes increasingly perturbed with aging so the use of probiotics can be a strategy for maintaining a balanced gut microbiome. A previous report showed that Bifidobacterium animalis subsp. lactis BPL1™ induces through its lipoteichoic acid (LTA) fat reduction activities via the insulin/IGF-1 signaling pathway. Here, we have delved into the mechanism of action, eliminating alternative pathways as putative mechanisms. Furthermore, we have identified that BPL1™, its heat treated form (BPL1™ HT) and its LTA prolong longevity in Caenorhabditis elegans (C. elegans) in an insulin/IGF-1-dependent mechanism, and its consumption improves the oxidative stress response, gut permeability and protection against pathogenic infections. Furthermore, positive effects on C. elegans stress-related behaviors and in the Alzheimer’s Disease model were found, highlighting the potential of the strain in improving the cognitive functions and proteotoxicity in the nematode. These results indicate the pivotal role of the IGF-1 pathway in the activity of the strain and pave the way for potential applications of BPL1™, BPL1™ HT and its LTA in the field of longevity and age-related markers. Full article

Nutrition has crucial effects and a significant role in disease prevention. Recently, nutraceuticals have attracted much attention in scientific research due to their pleiotropic effects and relatively non-toxic behavior. Among the biological effects displayed by plants belonging to the Lamiaceae family, such as antibacterial, anticancer, anti-inflammatory, and anticholinesterase, sage is well known for its antioxidant properties and is a rich source of numerous compounds that are biologically active, amongst them polyphenols, with more than 160 types identified. In this review we summarized some of the significant studies published in the last decade reporting the most employed extraction methods and the different assays that are useful for establishing the antioxidant properties of some sage species. Even though the scientific literature contains plenty of data regarding the antioxidant properties of many sage species, further studies are needed in order to gain a deeper understanding of the mechanism of action and the compounds responsible for their antioxidant activity. Finally, it should be taken into account that the data on the antioxidant properties of sage extracts are often difficult to compare with each other, since a series of variables in the extraction procedures, the type of assay used, and standardization may affect the final result. Full article

Inflammatory Bowel Diseases (IBD) are a group of chronic, inflammatory disorders of the gut. The incidence and activity of IBD are determined by both genetic and environmental factors. Among these factors, polymorphisms in genes related to autophagy and the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) have been consistently associated with IBD. We show that NSAIDs induce mitochondrial stress and mitophagy in intestinal epithelial cells. In an altered mitophagy context simulating that observed in IBD patients, NSAID-induced mitochondrial stress leads to the release of mitochondrial components, which act as Danger Associated Molecular Patterns with pro-inflammatory potential. Furthermore, colonic organoids from Crohn’s disease patients and healthy donors show activation of the mitochondrial Unfolded Protein Response (UPR^mt) upon treatment with ibuprofen. Finally, colon biopsies from Crohn’s disease patients in remission or with low-to-moderate activity also show expression of genes involved in UPR^mt, while patients with severe activity show no increase compared to healthy donors. Our results suggest the involvement of mitochondria in the mechanisms triggering inflammation in IBD after NSAID use. Moreover, our results highlight the clinical relevance of mitochondrial stress and activation of the UPR^mt pathway in the pathophysiology of Crohn’s disease. Full article

Multiple system atrophy (MSA) is generally a sporadic neurodegenerative disease which ranks among atypical Parkinson’s syndromes. The main clinical manifestation is a combination of autonomic dysfunction and parkinsonism and/or cerebellar disability. The disease may resemble other Parkinsonian syndromes, such as Parkinson’s disease (PD) or progressive supranuclear palsy (PSP), from which MSA could be hardly distinguishable during the first years of progression. Due to the lack of a reliable and easily accessible biomarker, the diagnosis is still based primarily on the clinical picture. Recently, reduced levels of coenzyme Q10 (CoQ10) were described in MSA in various tissues, including the central nervous system. The aim of our study was to verify whether the level of CoQ10 in plasma and lymphocytes could serve as an easily available diagnostic biomarker of MSA. The study reported significantly lower levels of CoQ10 in the lymphocytes of patients with MSA compared to patients with PD and controls. The reduction in CoQ10 levels in lymphocytes correlated with the increasing degree of clinical involvement of patients with MSA. CoQ10 levels in lymphocytes seem to be a potential biomarker of disease progression. Full article

Reactive oxygen species (ROS) are the initiators in foods and in the stomach of oxidized dietary lipids, proteins, and lipid-oxidation end-products (ALEs), inducing in humans the development of several chronic diseases and cancer. Epidemiological, human clinical and animal studies supported the role of dietary polyphenols and derivatives in prevention of development of such chronic diseases. There is much evidence that polyphenols/derivatives at the right timing and concentration, which is critical, acts mostly in the aerobic stomach and generally in the gastrointestinal tract as reducing agents, scavengers of free radicals, trappers of reactive carbonyls, modulators of enzyme activity, generators of beneficial gut microbiota and effectors of cellular signaling. In the blood system, at low concentration, they act as generators of electrophiles and low concentration of H₂O₂, acting mostly as cellular signaling, activating the PI3K/Akt-mediated Nrf2/eNOS pathways and inhibiting the inflammatory transcription factor NF-κB, inducing the cells, organs and organism for eustress, adaptation and surviving. Full article