Antioxidants

23 pages, 2670 KiB

Open AccessReview

The Role of Extracellular Vesicles in Aging and Age-Related Disorders

by Bharathi Hassan Ganesh, Himabindu Padinjarathil, Ramya Lakshmi Rajendran, Prasanna Ramani, Prakash Gangadaran and Byeong-Cheol Ahn

Antioxidants 2025, 14(2), 177; https://doi.org/10.3390/antiox14020177 - 3 Feb 2025

Abstract

A variety of molecular and cellular changes distinguish the multifaceted biological process of aging. Recent studies in this decade have demonstrated the essential role of extracellular vesicles (EVs) in the aging process. Mitochondrial malfunction and increased oxidative stress are major contributors for the [...] Read more.

A variety of molecular and cellular changes distinguish the multifaceted biological process of aging. Recent studies in this decade have demonstrated the essential role of extracellular vesicles (EVs) in the aging process. Mitochondrial malfunction and increased oxidative stress are major contributors for the aging process. This review investigates the role of EVs in intercellular communication, tissue regeneration, and inflammation in the context of aging. We also discuss the exosome and its utility to reduce oxidative stress, which is a key part of aging, as well as the possibility of using the exosomes (EVs) as anti-aging drugs. Changes in cargo composition can influence the aging phenotype and impact the functionality of cells and tissues. Additionally, the role of EVs in oxidative stress during the aging process addresses potential treatment strategies and the development of biomarkers for age-associated disorders. The review also highlighted the role of exosomes in providing antioxidant properties, which help reduce excessive reactive oxygen species (ROS) and strengthen cellular defenses against oxidative stress. Additionally, it emphasized the role of extracellular vesicles (EVs) in age-related pathologies, such as neurodegenerative diseases, cardiovascular disorders, and immunosenescence, offering insights into targeted interventions for promoting healthy aging. This article provides a comprehensive analysis of the current body of knowledge regarding the therapeutic effects of EVs on aging, with a particular emphasis on the implications of this emerging field of research and its relationship to oxidative stress. Full article

(This article belongs to the Special Issue The OxInflammation Process and Tissue Repair)

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12 pages, 3043 KiB

Open AccessArticle

Analysis of Singlet Oxygen Luminescence Generated By Protoporphyrin IX

by Vikas Vikas, Weibing Yang, Brian C. Wilson, Timothy C. Zhu and Robert H. Hadfield

Antioxidants 2025, 14(2), 176; https://doi.org/10.3390/antiox14020176 - 31 Jan 2025

Abstract

The effectiveness of photodynamic therapy (PDT) for cancer treatment relies on the generation of cytotoxic singlet oxygen (¹O₂) in type II PDT. Hence, monitoring of ¹O₂ generation during PDT enables optimal treatment delivery to the tumor target [...] Read more.

The effectiveness of photodynamic therapy (PDT) for cancer treatment relies on the generation of cytotoxic singlet oxygen (¹O₂) in type II PDT. Hence, monitoring of ¹O₂ generation during PDT enables optimal treatment delivery to the tumor target with reduced off-target effects. Direct ¹O₂ observation by measuring its luminescence at 1270 nm remains challenging due to the very weak signal. This study presents ¹O₂ luminescence measurements using a time-resolved singlet oxygen luminescence detection system (TSOLD) applied to protoporphyrin IX (PpIX) in different solvents (ethanol and acetone) and biological media (bovine serum albumin and agarose-based solid phantom). The compact experimental setup includes a nanosecond diode laser with a function generator, a cuvette with photosensitizer solution, optical filtering and mirrors, an InGaAs single-photon avalanche diode detector, and time-tagger electronics. Increasing the concentration of PpIX in these media from 1 to 10 µg/g resulted in a 3–5 × increase in the ¹O₂ luminescence signal. Furthermore, increasing light scattering in the sample using Intralipid from 0.1 to 1% led to a decrease in the ¹O₂ luminescence signal and lifetime. These results confirm the marked effect of the microenvironment on the ¹O₂ signal and, hence, on the photodynamic efficacy. Full article

(This article belongs to the Special Issue Reactive Oxygen Species and Growth Factors in Photodynamic Therapy (PDT), Photobiomodulation (PBM), and Radiation Therapy (RT))

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24 pages, 11816 KiB

Open AccessArticle

Coffee Compounds Protection Against Lipotoxicity Is Associated with Lipid Droplet Formation and Antioxidant Response in Primary Rat Hepatocytes

by Johanna C. Arroyave-Ospina, Magnolia Martínez, Manon Buist-Homan, Victoria Palasantzas, Marco Arrese and Han Moshage

Antioxidants 2025, 14(2), 175; https://doi.org/10.3390/antiox14020175 - 31 Jan 2025

Abstract

Metabolic dysfunction associated with steatotic liver disease (MASLD) is the result of disturbed lipid metabolism. In MASLD, the accumulation of free fatty acids (FFAs) in hepatocytes causes lipotoxicity mediated by oxidative stress. Coffee compounds are known for their beneficial effects in MASLD; however, [...] Read more.

Metabolic dysfunction associated with steatotic liver disease (MASLD) is the result of disturbed lipid metabolism. In MASLD, the accumulation of free fatty acids (FFAs) in hepatocytes causes lipotoxicity mediated by oxidative stress. Coffee compounds are known for their beneficial effects in MASLD; however, the mechanisms still need to be further explored. The aim of this study was to elucidate the protective mechanisms of coffee compounds against palmitate-induced lipotoxicity in primary hepatocytes. Methods: Primary hepatocytes were isolated from male Wistar rats and treated with palmitate (1 mmol/L) in combination with caffeine (CF: 1 mmol/L) or chlorogenic acid (CGA: 5 µmol/L). Mitochondrial ROS production, palmitate-induced necrosis, antioxidant response, ER stress markers and lipid droplet (LD) formation were assessed. Monoacylglycerols 2-SG (2-Stearolylglycerol), 2-OG (2-Oleoylglycerol) and SCD-1 (Stearoyl-CoA Desaturase 1) inhibitors were used to modulate LD formation. LD formation in steatotic Zucker rat hepatocytes was also investigated. Results: CF and CGA prevented palmitate-induced cell death and reduced ROS production. CF and CGA induced the antioxidant response, especially HO-1 expression, but had no significant effect on ER stress markers. CF and CGA increased LD formation in palmitate-treated cells. This effect was significantly reduced by 2-SG and SCD-1 inhibitors but enhanced by 2-OG. Lipid droplets were associated with lower palmitate toxicity and reduced ROS production. Conclusions: CF and CGA protect hepatocytes from lipotoxicity via modulation of the antioxidant response and enhance lipid droplet formation via an SCD-1-dependent mechanism. Oxidative stress-related toxicity in hepatocytes can be prevented by enhancing LD formation. Full article

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

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25 pages, 18944 KiB

Open AccessArticle

Effects of Black Cumin Seed Extract on Pancreatic Islet β-Cell Proliferation and Hypoglycemic Activity in Streptozotocin-Induced Diabetic Rats

by Jongkyu Kim, Yoon-Seok Chun, Namkyu Yoon, Byungkwon Kim, Kiin Choi, Sae-Kwang Ku and Namju Lee

Antioxidants 2025, 14(2), 174; https://doi.org/10.3390/antiox14020174 - 31 Jan 2025

Abstract

Thymoquinone (TQ), a bioactive compound derived from black cumin seeds, is renowned for its potent anti-obesity and anti-diabetic properties. Due to the stability challenges of TQ, it has predominantly been utilized in oil formulations. This study aimed to enhance the stability of TQ [...] Read more.

Thymoquinone (TQ), a bioactive compound derived from black cumin seeds, is renowned for its potent anti-obesity and anti-diabetic properties. Due to the stability challenges of TQ, it has predominantly been utilized in oil formulations. This study aimed to enhance the stability of TQ and investigated the impact of consuming insoluble fiber from black cumin seeds on restoring antioxidant function compromised by diabetes and improving hyperglycemia management. We evaluated the restorative effects of a 35-day administration of black cumin seed extract (BCS) on antioxidant function impaired by streptozotocin (STZ)-induced diabetes, alongside structural and functional alterations in the pancreas, liver, and kidneys. The results demonstrated significant improvements in organ weight, particularly in pancreatic tissue. Moreover, BCS administration markedly suppressed the expression of key genes associated with pancreatic dysfunction and damage, including caspase-3, transforming growth factor-beta 1 (TGF-β1), and interleukin-1 beta (IL-1β). Through oral glucose tolerance tests (OGTTs), BCS was found to effectively regulate chronic hyperglycemia and exhibit potential for managing acute hyperglycemia. These findings suggest that BCS not only addresses both glycemic and non-glycemic complications of diabetes but also offers a safe, long-term solution. Consequently, BCS emerges as a promising therapeutic agent for hyperglycemia management, including in prediabetic stages. Full article

24 pages, 4300 KiB

Open AccessArticle

Screening and Whole-Genome Analysis of Probiotic Lactic Acid Bacteria with Potential Antioxidants from Yak Milk and Dairy Products in the Qinghai–Tibet Plateau

by Diyan Wu, Haichuan Li, Xuan Wang, Runtong Chen, Di Gong, Danfeng Long, Xiaodan Huang, Zhenchuang Tang and Ying Zhang

Antioxidants 2025, 14(2), 173; https://doi.org/10.3390/antiox14020173 - 31 Jan 2025

Abstract

This study aimed to isolate lactic acid bacteria (LAB) with strong antioxidant activity and potential probiotic properties from yak milk and dairy products in the Qinghai–Tibet Plateau. Initial screening of the isolates was performed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay and a hydrogen [...] Read more.

This study aimed to isolate lactic acid bacteria (LAB) with strong antioxidant activity and potential probiotic properties from yak milk and dairy products in the Qinghai–Tibet Plateau. Initial screening of the isolates was performed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging assay and a hydrogen peroxide tolerance test. Subsequently, the antioxidant capacity of the isolates was assessed through five distinct assays: 2,2′-azino-bis (3-ethylbenzthiazoline)-6-sulfonic acid (ABTS) radical scavenging ability, superoxide anion radical scavenging ability, hydroxyl radical scavenging ability, a DPPH scavenging assay, and a reducing activity assay. The strains with the stronger antioxidant potential were then further evaluated for their probiotic properties. Whole-genome sequencing was conducted on Lactobacillus plantarum QL01. Among 1205 isolates, 9 strains exhibited potential antioxidant capabilities. Following probiotic property evaluation, QL01 was identified as a safe candidate due to its strong growth, strong adhesion ability, and resilience to acidic, bile, and simulated gastrointestinal conditions. Genome analysis revealed that most of QL01’s genes were involved in carbohydrate metabolism. Further examination of antibiotic resistance and virulence factors confirmed its safety, meanwhile genes linked to adhesion and stress responses underscored its probiotic potential. In conclusion, QL01, a strong antioxidant strain, was successfully isolated, and its probiotic potential was confirmed through comprehensive in vitro and genomic analyses. Full article

(This article belongs to the Section Natural and Synthetic Antioxidants)

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20 pages, 4227 KiB

Open AccessArticle

PFKFB3 Connects Glycolytic Metabolism with Endothelial Dysfunction in Human and Rodent Obesity

by Robert K. Batori, Zsuzsanna Bordan, Caleb A. Padgett, Yuqing Huo, Feng Chen, Reem T. Atawia, Rudolf Lucas, Masuko Ushio-Fukai, Tohru Fukai, Eric J. Belin de Chantemele, David W. Stepp and David J. R. Fulton

Antioxidants 2025, 14(2), 172; https://doi.org/10.3390/antiox14020172 - 31 Jan 2025

Abstract

Obesity and type 2 diabetes (T2D) increase cardiovascular risk, largely due to altered metabolic state. An early consequence of T2D/obesity is the loss of endothelial function and impaired nitric oxide (NO) signaling. In blood vessels, endothelial nitric oxide synthase (eNOS) synthesizes NO to [...] Read more.

Obesity and type 2 diabetes (T2D) increase cardiovascular risk, largely due to altered metabolic state. An early consequence of T2D/obesity is the loss of endothelial function and impaired nitric oxide (NO) signaling. In blood vessels, endothelial nitric oxide synthase (eNOS) synthesizes NO to maintain vessel homeostasis. The biological actions of NO are compromised by superoxide that is generated by NADPH oxidases (NOXs). Herein we investigated how altered metabolism affects superoxide/NO balance in obesity. We found that eNOS expression and NO bioavailability are significantly decreased in endothelial cells (ECs) from T2D patients and animal models of obesity. In parallel, PFKFB3, a key glycolytic regulatory enzyme, is significantly increased in ECs of obese animals. EC overexpression of wild-type and a cytosol-restricted mutant PFKFB3 decreased NO production due to increased eNOS-T495 phosphorylation. PFKFB3 also blunted Akt-S473 phosphorylation, reducing stimulus-dependent phosphorylation of S1177 and the activation of eNOS. Furthermore, PFKFB3 enhanced the activities of NOX1 and NOX5, which are major contributors to endothelial dysfunction. Prolonged exposure of ECs to high glucose or TNFα, which are hallmarks of T2D, leads to increased PFKFB3 expression. These results demonstrate a novel functional relationship between endothelial metabolism, ROS, and NO balance that may contribute to endothelial dysfunction in obesity. Full article

(This article belongs to the Special Issue NADPH Oxidases (NOXs))

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20 pages, 10130 KiB

Open AccessArticle

Extra Virgin Olive Oil Polyphenol-Enriched Extracts Exert Antioxidant and Anti-Inflammatory Effects on Peripheral Blood Mononuclear Cells from Rheumatoid Arthritis Patients

by Bartolo Tamburini, Diana Di Liberto, Giovanni Pratelli, Chiara Rizzo, Lidia La Barbera, Marianna Lauricella, Daniela Carlisi, Antonella Maggio, Antonio Palumbo Piccionello, Antonella D’Anneo, Nadia Caccamo and Giuliana Guggino

Antioxidants 2025, 14(2), 171; https://doi.org/10.3390/antiox14020171 - 31 Jan 2025

Abstract

Rheumatoid arthritis (RA) is a long-term systemic autoimmune disorder that causes joint inflammation, swelling, pain, bone erosion, and deformities. Recent findings emphasize the anti-inflammatory and antioxidant properties of bioactive natural compounds, such as polyphenols extracted from plants and fruits, and their possible synergistic [...] Read more.

Rheumatoid arthritis (RA) is a long-term systemic autoimmune disorder that causes joint inflammation, swelling, pain, bone erosion, and deformities. Recent findings emphasize the anti-inflammatory and antioxidant properties of bioactive natural compounds, such as polyphenols extracted from plants and fruits, and their possible synergistic effect when used in combination with current therapies to improve the prognosis and symptoms of inflammatory rheumatic diseases. Here, we report that Sicilian extra virgin olive oil polyphenol-enriched extracts (PE-EVOOs) reduce intracellular reactive oxygen species (ROS) and pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1 β (IL-1β), in peripheral mononuclear cells (PBMCs) obtained from both RA patients and healthy subjects (HSs) treated with lipopolysaccharides (LPS) as a control. HPLC-ESI-MS analysis highlighted that PE-EVOOs are rich in different polyphenolic compounds responsible for many of the observed biological effects. At molecular levels, Western blotting analyses revealed that PE-EVOO treatment is associated with the downregulation of the phosphorylated and active form of the inflammatory transcription factor NF-κB and the pro-inflammatory enzyme cyclooxygenase 2 (COX2). In addition, PE-EVOOs upregulated the transcription factor Nrf2 and its target antioxidant enzyme catalase and manganese superoxide dismutase (MnSOD). Collectively, these results suggest a possible use of PE-EVOOs as potential adjuvants for the treatment of RA. Full article

(This article belongs to the Special Issue Advances in the Astonishing World of Phytochemicals: State-of-the-Art for Antioxidants—2nd Edition)

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20 pages, 10108 KiB

Open AccessArticle

Intense Caloric Restriction from Birth Protects the Heart Against Ischemia/Reperfusion Injury and Reduces Reactive Oxygen Species in Ovariectomized Rats

by Vinícius Lopes Cantuária, Cíntia Maria Rodrigues, Isabella Rocha Dias, Vinícius de Oliveira Ottone, Bruna Oliveira Costa, Lourdes Fernanda Godinho, Gabriela Silva, Marco Antônio Alves Schetino, Etel Rocha-Vieira, Marco Fabrício Dias-Peixoto and Kinulpe Honorato-Sampaio

Antioxidants 2025, 14(2), 169; https://doi.org/10.3390/antiox14020169 - 31 Jan 2025

Abstract

This study investigates the cardioprotective effects of intense caloric restriction (ICR) from birth in ovariectomized rats, a model of estrogen deficiency mimicking menopause. Our findings demonstrate that ICR significantly improved both basal and post-ischemic cardiac function, even in the absence of estrogens. The [...] Read more.

This study investigates the cardioprotective effects of intense caloric restriction (ICR) from birth in ovariectomized rats, a model of estrogen deficiency mimicking menopause. Our findings demonstrate that ICR significantly improved both basal and post-ischemic cardiac function, even in the absence of estrogens. The restricted animals exhibited enhanced cardiac contractility and relaxation, particularly after ischemia/reperfusion (I/R) injury, with superior functional recovery compared to control groups. Notably, ICR reduced key cardiometabolic risk factors, including blood pressure, heart rate, and adiposity, while improving glucose tolerance and insulin sensitivity. Additionally, while mitochondrial biogenesis remained unaffected, ICR preserved mitochondrial integrity by reducing the number of damaged mitochondria. This was linked to a reduction in oxidative stress, as evidenced by lower reactive oxygen species (ROS) production in the hearts of restricted animals. These results suggest that ICR offers a protective effect against cardiovascular dysfunction induced by estrogen depletion, potentially through enhanced antioxidant defenses and mitochondrial protection. Full article

(This article belongs to the Special Issue Novel Antioxidant Mechanisms for Health and Diseases)

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25 pages, 1261 KiB

Open AccessArticle

Energy Intake-Dependent Genetic Associations with Obesity Risk: BDNF Val66Met Polymorphism and Interactions with Dietary Bioactive Compounds

by Ting Zhang and Sunmin Park

Antioxidants 2025, 14(2), 170; https://doi.org/10.3390/antiox14020170 - 30 Jan 2025

Abstract

Obesity represents a complex interplay between genetics, nutrition, and lifestyle. This study aimed to elucidate the intricate relationship between genetic variants, energy intake, and bioactive compounds in influencing obesity risk, particularly in low energy intake, to reveal how dietary intake modulates molecular-level interactions. [...] Read more.

Obesity represents a complex interplay between genetics, nutrition, and lifestyle. This study aimed to elucidate the intricate relationship between genetic variants, energy intake, and bioactive compounds in influencing obesity risk, particularly in low energy intake, to reveal how dietary intake modulates molecular-level interactions. We analyzed 53,117 participants stratified by obesity status and energy intake levels. Genome-wide association studies explored the genetic variants associated with obesity risk in low-energy- and high-energy-intake subgroups. Advanced computational approaches, including molecular docking, k-means clustering, and uniform manifold approximation and projection (UMAP), were employed to analyze interactions between missense variants and natural compounds. Ten genetic variants were significantly associated with obesity, particularly in participants with low energy intake. The most prominent variants included brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265). Molecular docking identified 152 bioactive compounds with strong binding affinity to BDNF Val66Met, including 107 compounds binding to both wild and mutant types. Citrus fruits and green vegetables showed selective binding to the mutant type. Antioxidant nutrient intake (anthocyanins, isoflavonoids, vitamins C and E, selenium) was higher in lean versus obese individuals in the high-energy-intake group. Alcohol consumption and selenium intake modulated polygenic risk scores’ influence on obesity risk in high-energy-intake individuals. Notably, citrus fruit intake correlated with lower BMI across all BDNF rs6265 genotypes. In conclusion, energy intake-specific genetic associations with obesity and identifies potential bioactive compounds for targeted interventions. The findings suggest that antioxidant nutrient intake, particularly from citrus fruits, may help manage obesity risk, especially in individuals with specific genetic variants. Full article

(This article belongs to the Special Issue The Role of Natural Antioxidants in Fruits and Vegetables in Human Health)

25 pages, 2140 KiB

Open AccessArticle

Curcumin Attenuates Fumonisin B1-Induced PK-15 Cell Apoptosis by Upregulating miR-1249 Expression to Inhibit the IRE1/MKK7/JNK/CASPASE3 Signaling Pathway

by Jia Chen, Dongwei Xiong and Miao Long

Antioxidants 2025, 14(2), 168; https://doi.org/10.3390/antiox14020168 - 30 Jan 2025

Abstract

Fumonisin B1 (FB1) is an important toxin which poses global concerns in terms of food safety. Curcumin (Cur), a natural polyphenolic compound, has strong antioxidant and anti-inflammatory effects. Meanwhile, the mechanisms underlying the mitigation of FB1-induced toxicity by Cur are not fully understood, [...] Read more.

Fumonisin B1 (FB1) is an important toxin which poses global concerns in terms of food safety. Curcumin (Cur), a natural polyphenolic compound, has strong antioxidant and anti-inflammatory effects. Meanwhile, the mechanisms underlying the mitigation of FB1-induced toxicity by Cur are not fully understood, limiting its potential application as a novel feed additive to prevent FB1 toxicity. In this study, porcine kidney cells (PK-15) were used as an experimental model, utilizing mRNA and miRNA transcriptome technologies. The results revealed that Cur upregulated miR-1249 and inhibited the target gene Ern1 in the PK-15 cells, thereby suppressing the IRE1/MKK7/JNK/CASPASE3 endoplasmic reticulum (ER) stress pathway and alleviating FB1-induced cell apoptosis. Cell transfection experiments confirmed that Cur effectively attenuated the apoptosis induced by ER stress following transfection with a miR-1249 inhibitor. Similarly, transfection with a miR-1249 mimic alleviated the ER stress and FB1-induced PK-15 cell apoptosis. These findings reveal that Cur mitigates FB1-induced ER stress and significantly reduces apoptotic damage in porcine kidney cells. Full article

13 pages, 1431 KiB

Open AccessArticle

The Role of Paraoxonase-1 Activity, Apolipoprotein B Levels, and Apolipoprotein B/Apolipoprotein A-I Ratio as Risk Markers for Aortic Stenosis in Patients with a Bicuspid Aortic Valve

by Maria Kwiatkowska, Agnieszka Mickiewicz, Aleksandra Krzesińska, Agnieszka Kuchta, Maciej Jankowski, Marcin Gruchała and Marcin Fijałkowski

Antioxidants 2025, 14(2), 167; https://doi.org/10.3390/antiox14020167 - 30 Jan 2025

Abstract

The bicuspid aortic valve (BAV) is commonly associated with the early degeneration of the aortic valve. Up to 45% of BAV patients over the age of 50 develop aortic stenosis (AS). Although published data indicate a robust interplay between lipids and calcific AS [...] Read more.

The bicuspid aortic valve (BAV) is commonly associated with the early degeneration of the aortic valve. Up to 45% of BAV patients over the age of 50 develop aortic stenosis (AS). Although published data indicate a robust interplay between lipids and calcific AS in tricuspid aortic valve patients, the studies on the BAV population are lacking. We aimed to evaluate the association between selected lipid markers and the occurrence of AS in BAV patients. Methods: The study included 76 adults (21 female) with a BAV diagnosed by echocardiography, divided by age and AS diagnosis. Biochemical parameters concentrations in serum were measured: high density lipoprotein cholesterol (HDL-C) levels by standard enzymatic colorimetric tests, low density lipoprotein cholesterol (LDL-C) levels by the Friedewald formula, apolipoprotein A-I (Apo AI) and apolipoprotein B (Apo B) serum concentration by the nephelometric method, and paraoxonase-1 activity (PON-1 ASE) and arylesterase activity (PON-1 ARE) based on paraoxon and phenyl acetate hydrolysis. Results: A total of 54 patients (15 female) were more than 45 years old and 22 (6 female) were 45 or less years old. BAV patients with AS aged ≤45 had higher levels of Apo B, compared to those without AS [110.5 (102–132) vs. 95.6 (77–101) mg/d; p 0.044]. Similarly, Apo B/Apo AI ratio was higher in BAV patients with AS aged ≤45, compared to those without AS [(0.8 (0.7–1) vs. 0.6 (0.5–0.7); p 0.029]. In the group aged ≤45, Apo B showed a positive correlation with the aortic valve peak transvalvular velocity (AV Vmax) measurement (R Spearman 0.6, p 0.004). We found also that, among young BAV patients, those with AS had a lower level of PON-1 ARE compared to the cohort without AS [63.4 (52–80) vs. 85.3 (70–102); p 0.012]. We did not find any differences in lipid parameters in patients aged >45. Conclusions The metabolic link between Apo B level and Apo B/AI ratio with AS presence in BAV patients under 45 years of age suggests a significant impact of these parameters on the earlier development of AS in the BAV population. Molecules associated with high density lipoprotein and its antioxidant function, such as PON1, are valuable markers for AS development, compared to HDL-C and LDL-C levels. Full article

(This article belongs to the Special Issue Antioxidant Role of High-Density Lipoprotein)

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24 pages, 7385 KiB

Open AccessArticle

Therapeutic Effects of Lavender Oil on Streptozotocin-Induced Diabetes Mellitus and Experimental Thrombosis

by Valeriu Mihai But, Vasile Rus, Tamás Ilyés, Mădălina Luciana Gherman, Ioana Cristina Stănescu, Sorana D. Bolboacă and Adriana Elena Bulboacă

Antioxidants 2025, 14(2), 166; https://doi.org/10.3390/antiox14020166 - 30 Jan 2025

Abstract

Diabetes mellitus is a metabolic disorder associated with oxidative stress, inflammation, and coagulation disturbances, which contribute to microvascular and macrovascular complications. We evaluated the therapeutic effects of lavender oil (Lavandula angustifolia) in a streptozotocin (STZ)-induced rat model of type 1 diabetes [...] Read more.

Diabetes mellitus is a metabolic disorder associated with oxidative stress, inflammation, and coagulation disturbances, which contribute to microvascular and macrovascular complications. We evaluated the therapeutic effects of lavender oil (Lavandula angustifolia) in a streptozotocin (STZ)-induced rat model of type 1 diabetes mellitus (T1DM) with experimentally induced thrombosis. Sixty male Wistar rats were divided into control, thrombosis, diabetes, thrombosis–diabetes, and lavender oil pretreatment groups (100 and 200 mg/kg body weight [bw]). Lavender oil exhibited dose-dependent benefits, with the 200 mg/kg bw dose leading to significant reductions in proinflammatory cytokines (e.g., tumor necrosis factor α (TNF-α); regulated upon activation, normal T cell expressed and secreted (RANTES); and monocyte chemoattractant protein-1 (MCP-1)) and oxidative stress, along with improved glycemic control, the partial restoration of C-peptide levels, and the attenuation of matrix metalloproteinase 2 and 9 (MMP-2 and MMP-9) activity (p < 0.0001). Histopathological and coagulation analyses confirmed its organ-protective and antithrombotic effects, including reduced tissue damage, vascular inflammation, and thrombus formation, and prolonged bleeding and clotting times. Our findings suggest that lavender oil exhibits dose-dependent antioxidant, anti-inflammatory, hypoglycemic, and organ-protective effects, indicating its potential as a complementary therapy for managing inflammation in T1DM with or without thrombosis. Full article

(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)

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17 pages, 553 KiB

Open AccessReview

Association Between Zinc Levels and the Impact of Its Deficiency on Idiopathic Male Infertility: An Up-to-Date Review

by Nebojša Zečević, Aleksandra Veselinović, Milan Perović and Aleksandar Stojsavljević

Antioxidants 2025, 14(2), 165; https://doi.org/10.3390/antiox14020165 - 29 Jan 2025

Abstract

Background: Zinc (Zn) is an essential metal that plays a critical role in normal testicular development, spermatogenesis, prevention of sperm degradation, and overall male fertility. This review aims to offer a comprehensive and current overview of seminal plasma Zn levels in fertile men [...] Read more.

Background: Zinc (Zn) is an essential metal that plays a critical role in normal testicular development, spermatogenesis, prevention of sperm degradation, and overall male fertility. This review aims to offer a comprehensive and current overview of seminal plasma Zn levels in fertile men worldwide. It also aims to compare Zn levels in seminal plasma and blood (serum/plasma) between infertile men (cases) and fertile men (controls), examine the impact of Zn on sperm quality and the reproductive hormone, and highlight the effects of Zn supplementation therapy in male infertility. Methods: To achieve these goals, peer-reviewed studies from 2000 to 2024 were interrogated with regard to strict inclusion/exclusion criteria and were then thoroughly reviewed and analyzed. Results: Our findings indicate that maintaining optimal seminal plasma Zn levels is crucial, as low Zn levels are linked to impaired spermatogenesis and male infertility, while high Zn levels can cause oxidative stress and other changes that contribute to infertility. Seminal plasma Zn levels from 100 to 200 mg/L among fertile men worldwide can be roughly considered safe. Comparative analysis showed that a greater number of studies reported lower levels of seminal Zn in cases than in controls. Research into the impact of Zn levels in seminal plasma has shown that, although the results are not yet conclusive, altered (non-normal) Zn levels could influence semen parameters—particularly motility, morphology, and sperm count—and the level of the reproductive hormone, testosterone. Zinc-deficient infertile men could benefit from supplement therapy. Conclusions: Assessment of seminal plasma Zn levels in infertile men could provide valuable information and aid in diagnosis and treatment planning. Full article

(This article belongs to the Section Antioxidant Enzyme Systems)

29 pages, 610 KiB

Open AccessArticle

Antioxidant, Antithrombotic and Anti-Inflammatory Properties of Amphiphilic Bioactives from Water Kefir Grains and Its Apple Pomace-Based Fermented Beverage

by Dimitra Papadopoulou, Vasiliki Chrysikopoulou, Aikaterini Rampaouni, Christos Plakidis, Anna Ofrydopoulou, Katie Shiels, Sushanta Kumar Saha and Alexandros Tsoupras

Antioxidants 2025, 14(2), 164; https://doi.org/10.3390/antiox14020164 - 29 Jan 2025

Abstract

Kefir-based fermentation products exhibit antioxidant and anti-inflammatory effects against oxidative stress, inflammation, platelet activation and aggregation, and other related manifestations, thereby preventing the onset and development of several chronic diseases. Specifically, water kefir, a symbiotic culture of various microorganisms used for the production [...] Read more.

Kefir-based fermentation products exhibit antioxidant and anti-inflammatory effects against oxidative stress, inflammation, platelet activation and aggregation, and other related manifestations, thereby preventing the onset and development of several chronic diseases. Specifically, water kefir, a symbiotic culture of various microorganisms used for the production of several bio-functional fermented products, has been proposed for its health-promoting properties. Thus, water kefir grains and its apple pomace-based fermentation beverage were studied for bioactive amphiphilic and lipophilic lipid compounds with antioxidant, antithrombotic, and anti-inflammatory properties. Total lipids(TL) were extracted and further separated into their total amphiphilic (TAC) and total lipophilic content (TLC), in which the total phenolic and carotenoid contents (TPC and TCC, respectively) and the fatty acid content of the polar lipids (PL) were quantified, while the antioxidant activity of both TAC and TLC were assessed in vitro, by the ABTS, DPPH, and FRAP bioassays, along with the anti-inflammatory and antithrombotic activity of TAC against human platelet aggregation induced by the thrombo-inflammatory mediator, platelet-activating factor (PAF) or standard platelet agonists like ADP.ATR-FTIR spectra facilitated the detection of specific structural, functional groups of phenolic, flavonoid, and carotenoid antioxidants, while LC−MS analysis revealed the presence of specific anti-inflammatory and antithrombotic PL bioactives bearing unsaturated fatty acids in their structures, with favorable omega-6 (n−6)/omega-3 (n−3)polyunsaturated fatty acids (PUFA), which further support the findings that the most potent antioxidant, anti-inflammatory and antithrombotic bioactivities were observed in the TAC extracts, in both water kefir grains and beverage cases. The detection of such bioactive components in both the uncultured water kefir grains and in the cultured beverage further supports the contribution of water kefir microorganisms to the bioactivity and the bio-functionality of the final fermented product. Nevertheless, the extracts of the beverage showed much stronger antioxidant, anti-inflammatory, and antithrombotic activities, which further suggests that during the culture process for producing this beverage, not only was the presence of bioactive compounds produced by kefir microflora present, but biochemical alterations during fermentation of bioactive components derived from apple pomace also seemed to have taken place, contributing to the higher bio-functionality observed in the apple pomace—water kefir-based beverage, even when compared to the unfermented apple pomace. The overall findings support further studies on the use of water kefir and/or apple pomace as viable sources of antioxidant, anti-inflammatory, and antithrombotic amphiphilic bioactive compounds for the production of novel health-promoting bio-functional fermented products. Full article

(This article belongs to the Special Issue Antioxidants from Sustainable Food Sources)

18 pages, 2376 KiB

Open AccessArticle

Myocardial DYRK1B Expression Is Increased in Patients with Impaired Cardiac Contractility and Sleep-Disordered Breathing

by Fatma Bayram, Philipp Hegner, Anna-Maria Lauerer, Sönke Schildt, Dominik Wermers, Maria Johanna Baier, Julian Mustroph, Maria Tafelmeier, Zdenek Provaznik, Christof Schmid, Lars Siegfried Maier, Stefan Wagner, Michael Arzt and Simon Lebek

Antioxidants 2025, 14(2), 163; https://doi.org/10.3390/antiox14020163 - 29 Jan 2025

Abstract

Heart failure and cardiovascular disease represent a significant burden on healthcare systems worldwide. Recent evidence associates an increased expression of the dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) with an impaired cardiac function in mice. However, there remains a paucity of data on myocardial [...] Read more.

Heart failure and cardiovascular disease represent a significant burden on healthcare systems worldwide. Recent evidence associates an increased expression of the dual-specificity tyrosine phosphorylation-regulated kinase 1B (DYRK1B) with an impaired cardiac function in mice. However, there remains a paucity of data on myocardial DYRK1B expression in patients with cardiovascular disease in the context of other comorbidities. In our study, we examined DYRK1B mRNA expression in human right atrial appendage biopsies from 159 patients undergoing elective coronary artery bypass surgery. Each patient was tested for sleep-disordered breathing the night prior to surgery. In this large representative study cohort with cardiovascular high-risk patients, we found that an impaired cardiac function as well as sleep-disordered breathing (SDB), including various oxidative stress parameters, were associated with an increased myocardial DYRK1B expression. A multivariate regression analysis revealed left ventricular ejection fraction and the presence of SDB as significant predictors of the myocardial DYRK1B expression independent of other clinical covariates. Based on these findings, DYRK1B represents a promising molecular target in patients with heart failure and reduced ejection fraction as well in patients with sleep-disordered breathing. Full article

(This article belongs to the Special Issue Harnessing Redox Status and Novel Molecular Signals and Targets Involved in Oxidative Stress to Afford Cardioprotection: From Experimental Insights to Clinical Applications)

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19 pages, 7584 KiB

Open AccessArticle

Causal Impacts of Psychiatric Disorders on Cognition and the Mediating Effect of Oxidative Stress: A Mendelian Randomization Study

by Yan Gao, Dandan Wang, Qian Wang, Jinfeng Wang, Shuhui Li, Tianqi Wang, Xiaowen Hu and Chunling Wan

Antioxidants 2025, 14(2), 162; https://doi.org/10.3390/antiox14020162 - 29 Jan 2025

Abstract

Many psychiatric disorders are associated with major cognitive deficits. However, it is uncertain whether these deficits develop as a result of psychiatric disorders and what shared risk factors might mediate this relationship. Here, we utilized the Mendelian randomization (MR) analysis to investigate the [...] Read more.

Many psychiatric disorders are associated with major cognitive deficits. However, it is uncertain whether these deficits develop as a result of psychiatric disorders and what shared risk factors might mediate this relationship. Here, we utilized the Mendelian randomization (MR) analysis to investigate the complex causal relationship between nine major psychiatric disorders and three cognitive phenotypes, while also examining the potential mediating role of oxidative stress as a shared biological underpinning. Schizophrenia (SZ), major depressive disorder (MDD), and attention deficit hyperactivity disorder (ADHD) showed a decreasing effect on cognitive performance, intelligence, and education, while bipolar disorder (BPD) increased educational attainment. MR-Clust results exhibit the shared genetic basis between SZ and other psychiatric disorders in relation to cognitive function. Furthermore, when oxidative stress was considered as a potential mediating factor, the associations between SZ and the three dimensions of cognition, as well as between MDD and intelligence and ADHD and intelligence, exhibited larger effect sizes than the overall. Mediation MR analysis also supported the causal effects between psychiatric disorders and cognition via oxidative stress traits, including carotene, vitamin E, bilirubin, and uric acid. Finally, summary-based MR identified 29 potential causal associations of oxidative stress genes with both cognitive performance and psychiatric disorders. Our findings highlight the importance of considering oxidative stress in understanding and potentially treating cognitive impairments associated with psychiatric conditions. Full article

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19 pages, 3898 KiB

Open AccessArticle

High Rosmarinic Acid Content Melissa officinalis L. Phytocomplex Modulates Microglia Neuroinflammation Induced by High Glucose

by Giacomina Videtta, Chiara Sasia and Nicoletta Galeotti

Antioxidants 2025, 14(2), 161; https://doi.org/10.3390/antiox14020161 - 29 Jan 2025

Abstract

Diabetic patients experience hyperglycemia, which can affect multiple organs, including brain function, leading to disabling neurological complications. Hyperglycemia plays a key role in promoting neuroinflammation, the most common complication in diabetic individuals, through the activation of microglia. Attenuating hyperglycemia-related neuroinflammation in microglia may [...] Read more.

Diabetic patients experience hyperglycemia, which can affect multiple organs, including brain function, leading to disabling neurological complications. Hyperglycemia plays a key role in promoting neuroinflammation, the most common complication in diabetic individuals, through the activation of microglia. Attenuating hyperglycemia-related neuroinflammation in microglia may reduce diabetes-associated neurological comorbidities. Natural remedies containing phenolic compounds have shown efficacy in mitigating microglia-mediated neuroinflammation. The aim of this study was to investigate the potential of a Melissa officinalis L. (MO) phytocomplex, obtained from plant cell cultures and enriched in its main polyphenolic constituent, rosmarinic acid (RA), in attenuating hyperglycemia-induced neuroinflammation in microglia. A time-course morphological analysis of BV2 microglial cells exposed to high glucose (HG) levels showed a shift towards a proinflammatory phenotype, peaking after 48 h, which was reversed by pretreatment with MO. Biochemical assays revealed increased expression of the microglial marker CD11b (187%), activation of the NF-κB pathway (179%), expression of iNOS (225%), enhanced phosphorylation of ERK1/2 (180%), and increased expression of the proinflammatory cytokine IL-6 (173%). Pretreatment with MO prevented the aberrant expression of these proinflammatory mediators and restored SIRT1 levels. Exposure of neuronal SH-SY5Y cells to the conditioned medium from HG-exposed microglia significantly reduced cell viability. MO counteracted this effect, exhibiting neuroprotective activity. RA showed efficacy comparable to that of MO. In conclusion, MO and RA attenuated microglia-mediated oxidative imbalance and neuroinflammation under HG exposure by inhibiting the morphological shift toward a proinflammatory phenotype induced by HG and abrogating the subsequent activation of the downstream ERK1/2–NF-κB–iNOS pathway. Full article

(This article belongs to the Special Issue Plant Antioxidants, Inflammation, and Chronic Disease)

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19 pages, 5996 KiB

Open AccessArticle

Effect of Photoperiod on Ascorbic Acid Metabolism Regulation and Accumulation in Rapeseed (Brassica napus L.) Seedlings

by Chao Wang, Lieqiong Kuang, Ze Tian, Xinfa Wang, Jinxing Tu, Hanzhong Wang and Xiaoling Dun

Antioxidants 2025, 14(2), 160; https://doi.org/10.3390/antiox14020160 - 29 Jan 2025

Abstract

Ascorbic acid (AsA) is an important antioxidant for human health. The concept of “oil-vegetable-duel-purpose” can significantly enhance the economic benefits of the rapeseed industry. Rapeseed, when utilized as a vegetable, serves as a valuable food source of AsA. In this study, we integrated [...] Read more.

Ascorbic acid (AsA) is an important antioxidant for human health. The concept of “oil-vegetable-duel-purpose” can significantly enhance the economic benefits of the rapeseed industry. Rapeseed, when utilized as a vegetable, serves as a valuable food source of AsA. In this study, we integrated transcriptome and metabolome analyses, along with substrate feeding, to identify the L-galactose pathway as the primary source for AsA production, which is primarily regulated by light. Through seven different photoperiod treatments from 12 h/12 h (light/dark) to 24 h/0 h, we found that AsA content increased with longer photoperiods, as well as chlorophyll, carotenoids, and soluble sugars. However, an excessively long photoperiod led to photooxidative stress, which negatively affected biomass accumulation in rapeseed seedlings and subsequently impacted the total accumulation of AsA. Furthermore, different enzymes respond differently to different photoperiods. Analysis of the correlation between the expression levels of AsA biosynthesis-related genes and AsA content highlighted a dynamic balancing mechanism of AsA metabolism in response to different photoperiods. The study revealed that the 16 h/8 h photoperiod is optimal for long-term AsA accumulation in rapeseed seedlings. However, extending the photoperiod before harvest can enhance AsA content without compromising yield. These findings offer novel insights into an effective strategy for the biofortification of AsA in rapeseed. Full article

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22 pages, 1127 KiB

Open AccessArticle

Elevated Serum Levels of Acid Sphingomyelinase in Female Patients with Episodic and Chronic Migraine

by Alberto Ouro, Mónica Castro-Mosquera, Mariña Rodríguez-Arrizabalaga, Manuel Debasa-Mouce, Antía Custodia, Marta Aramburu-Núñez, Daniel Romaus-Sanjurjo, Josefina Casas, Isabel Lema, José Castillo, Rogelio Leira and Tomás Sobrino

Antioxidants 2025, 14(2), 159; https://doi.org/10.3390/antiox14020159 - 29 Jan 2025

Abstract

Migraine is one of the most common neurological disorders and the second most disabling human condition. The molecular mechanisms of migraine have been linked to neuropeptide release, endothelial dysfunction, oxidative stress and inflammatory processes. Acid sphingomyelinase (aSMase) is a secreted enzyme that leads [...] Read more.

Migraine is one of the most common neurological disorders and the second most disabling human condition. The molecular mechanisms of migraine have been linked to neuropeptide release, endothelial dysfunction, oxidative stress and inflammatory processes. Acid sphingomyelinase (aSMase) is a secreted enzyme that leads to sphingomyelin degradation to produce ceramide. Its activity has been associated with several molecular processes involved in migraine. Therefore, this cross-sectional study aims to study the potential role of aSMase in patients with episodic and chronic migraine. In this cross-sectional pilot study, serum samples from female healthy controls (n = 23), episodic migraine (EM) patients (n = 31), and chronic migraine (CM) patients (n = 28) were studied. The total serum levels of aSMase were determined by ELISA. In addition, the serum levels of sphingomyelin (SM), dihydro-sphingomyelin (dhSM), ceramide (Cer), and dihydro-ceramide (dhCer) were determined by mass spectrometry as biomarkers involved in the main molecular pathways associated with aSMase. aSMase serum levels were found significantly elevated in both EM (3.62 ± 1.25 ng/mL) and CM (3.07 ± 0.95 ng/mL) compared with controls (1.58 ± 0.72 ng/mL) (p < 0.0001). ROC analysis showed an area under the curve (AUC) of 0.94 (95% CI: 0.89–0.99, p < 0.0001) and 0.90 (95% CI: 0.81–0.99, p < 0.0001) for EM and CM compared to controls, respectively. Regarding other biomarkers associated with aSMase’s pathways, total SM serum levels were significantly decreased in both EM (173,534 ± 39,096 pmol/mL, p < 0.01) and CM (158,459 ± 40,010 pmol/mL, p < 0.0001) compared to the control subjects (219,721 ± 36,950 pmol/mL). Elevated serum levels of aSMase were found in EM and CM patients compared to the control subjects. The decreased SM levels found in both EM and CM indicate that aSMase activity plays a role in migraine. Therefore, aSMase may constitute a new therapeutic target in migraine that should be further investigated. Full article

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