Antioxidants

19 pages, 13952 KiB

Open AccessArticle

Antioxidant and Anti-Inflammatory Effects of Crude Gastrodia elata Polysaccharides in UVB-Induced Acute Skin Damage

by Jiajia Liu, Xiaoqi Yang, Xing Huang, Yuan Luo, Qilin Zhang, Feng Wang, Yicen Lin and Lianbing Lin

Antioxidants 2025, 14(7), 894; https://doi.org/10.3390/antiox14070894 - 21 Jul 2025

Abstract

Ultraviolet B (UVB) irradiation drives skin photodamage, prompting exploration of natural therapeutics. This study investigated the reparative effects and mechanisms of crude Gastrodia elata polysaccharides (GP) on UVB-induced acute skin damage. GP was extracted from fresh G. elata via water extraction and alcohol [...] Read more.

Ultraviolet B (UVB) irradiation drives skin photodamage, prompting exploration of natural therapeutics. This study investigated the reparative effects and mechanisms of crude Gastrodia elata polysaccharides (GP) on UVB-induced acute skin damage. GP was extracted from fresh G. elata via water extraction and alcohol precipitation. It is a homogeneous polysaccharide with a weight-average molecular weight of 808.863 kDa, comprising Ara, Glc, Fru, and GalA. Histopathological analysis revealed that topical application of GP on the dorsal skin of mice effectively restored normal physiological structure, suppressing epidermal hyperplasia and collagen degradation. Biochemical assays showed that GP significantly reduced the activities of MPO and MDA following UVB exposure while restoring the enzymatic activities of SOD and GSH, thereby mitigating oxidative stress. Moreover, GP treatment markedly upregulated the anti-inflammatory cytokines TGF-β and IL-10 and downregulated the pro-inflammatory mediators IL-6, IL-1β, and TNF-α, suggesting robust anti-inflammatory effects. Transcriptomics revealed dual-phase mechanisms: Early repair (day 5) involved GP-mediated suppression of hyper inflammation and accelerated necrotic tissue clearance via pathway network modulation. Late phase (day 18) featured enhanced anti-inflammatory, antioxidant, and tissue regeneration processes through energy-sufficient, low-inflammatory pathway networks. Through a synergistic response involving antioxidation, anti-inflammation, promotion of collagen synthesis, and acceleration of skin barrier repair, GP achieves comprehensive repair of UVB-induced acute skin damage. Our findings not only establish GP as a potent natural alternative to synthetic photoprotective agents but also reveal novel pathway network interactions governing polysaccharide-mediated skin regeneration. Full article

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

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18 pages, 2470 KiB

Open AccessArticle

Preventive Gastroprotective Effect of a Functional Food Based on Quinoa (Chenopodium quinoa Willd.) and Quercetin in a Murine Model of Ibuprofen-Induced Gastric Damage

by Maribel Valenzuela-González, José Luis Cárdenas-López, Armando Burgos-Hernández, Norma Julieta Salazar-López, Manuel Viuda-Martos, Mónica A. Villegas-Ochoa, Gustavo Martínez-Coronilla, J. Abraham Domínguez-Avila, Shela Gorinstein, Gustavo A. González-Aguilar and Rosario Maribel Robles-Sánchez

Antioxidants 2025, 14(7), 893; https://doi.org/10.3390/antiox14070893 - 21 Jul 2025

Abstract

Nonsteroidal anti-inflammatory drug-based therapies are the cause of 20–30% cases of gastric lesions in chronic users worldwide. Co-medication with omeprazole (OMP) is the most commonly used option to prevent these lesions, although this carries risks of its own; thus, alternatives are being explored, [...] Read more.

Nonsteroidal anti-inflammatory drug-based therapies are the cause of 20–30% cases of gastric lesions in chronic users worldwide. Co-medication with omeprazole (OMP) is the most commonly used option to prevent these lesions, although this carries risks of its own; thus, alternatives are being explored, such as dietary antioxidant therapies. The objective of this study was to evaluate the gastroprotective activity of quinoa (Chenopodium quinoa Willd.) on ibuprofen (IBP)-induced gastric ulcers in a rat model. Quinoa cookies were formulated with heat-treated quinoa using microwave radiation. The intestinal bioaccessibility of phenols and flavonoids, and the antioxidant activity of microwaved quinoa cookies (MQCs) were notably higher than quinoa cookies without thermal treatment (RQCs): 132% TPC, 52% TFC, 1564% TEAC vs. 67% TPC, 24% TFC, and 958% TEAC, respectively. Basal diets were supplemented with MQCs (20%) and quercetin (Q, 0.20%) as a reference flavonoid and administered for 30 days. Gastric lesions were induced by intragastric IBP doses, with OMP treatment as a positive control. Gastric damage index (macroscopic study), histological score (microscopic study), and plasma antioxidant enzyme activity (SOD and CAT) were evaluated. Macroscopic results showed that the addition of MQCs, Q, and OMP decreased the gastric damage index (GDI) by 50%, 40%, and 3%, respectively, as compared to IBP (GDI 100%). Histological analyses showed neutrophil infiltration and congested blood vessels in IBP-treated tissues; in contrast, the experimental diet groups showed lower infiltration for MQC > OMP > Q, respectively. A significant increase in SOD and CAT enzyme activity was observed in the MQC and Q groups as compared to the IBP group. We conclude that a reduction in the GDI and histological score was observed in IBP-induced murine models fed diets containing 20% MQC and 0.20% Q, demonstrating a preventive gastroprotective effect. Full article

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

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21 pages, 2702 KiB

Open AccessArticle

Piperine Induces Apoptosis and Cell Cycle Arrest via Multiple Oxidative Stress Mechanisms and Regulation of PI3K/Akt and MAPK Signaling in Colorectal Cancer Cells

by Wan-Ling Chang, Jyun-Yu Peng, Chain-Lang Hong, Pei-Ching Li, Soi Moi Chye, Fung-Jou Lu, Huei-Yu Lin and Ching-Hsein Chen

Antioxidants 2025, 14(7), 892; https://doi.org/10.3390/antiox14070892 - 21 Jul 2025

Abstract

Piperine, a phytochemical alkaloid, exhibits notable anticancer properties in several cancer cell types. In this study, we investigated the mechanisms by which piperine induces cell death and apoptosis in colorectal cancer (CRC) cells, focusing on oxidative stress and key signaling pathways. Using MTT [...] Read more.

Piperine, a phytochemical alkaloid, exhibits notable anticancer properties in several cancer cell types. In this study, we investigated the mechanisms by which piperine induces cell death and apoptosis in colorectal cancer (CRC) cells, focusing on oxidative stress and key signaling pathways. Using MTT assay, flow cytometry, gene overexpression, and Western blot analysis, we observed that piperine significantly reduced cell viability, triggered G1 phase cell cycle arrest, and promoted apoptosis in DLD-1 cells. In addition, piperine effectively suppressed cell viability and induced apoptosis in other CRC cell lines, including SW480, HT-29, and Caco-2 cells. These effects were associated with increased intracellular reactive oxygen species (ROS) generation, mediated by the regulation of mitochondrial complex III, NADPH oxidase, and xanthine oxidase. Additionally, piperine modulated signaling pathways by inhibiting phosphoinositide 3-kinase (PI3K)/Akt, activating p38 and p-extracellular signal-regulated kinase (ERK). Pretreatment with antimycin A, apocynin, allopurinol, and PD98059, and the overexpression of p-Akt significantly recovered cell viability and reduced apoptosis, confirming the involvement of these pathways. This study is the first to demonstrate piperine induces apoptosis in CRC cells through a multifaceted oxidative stress mechanism and by critically modulating PI3K/Akt and ERK signaling pathways. Full article

(This article belongs to the Special Issue The Janus Face of Oxidative Stress in Normal and Pathological Conditions)

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16 pages, 4128 KiB

Open AccessArticle

Pemafibrate Ameliorates Steatotic Liver Disease Regardless of Endothelial Dysfunction in Mice

by Tomoyo Hara, Hiroki Yamagami, Ryoko Uemoto, Akiko Sekine, Yousuke Kaneko, Kohsuke Miyataka, Taiki Hori, Mayuko Ichimura-Shimizu, Masafumi Funamoto, Takeshi Harada, Tomoyuki Yuasa, Shingen Nakamura, Itsuro Endo, Ken-ichi Matsuoka, Yutaka Kawano, Koichi Tsuneyama, Yasumasa Ikeda and Ken-ichi Aihara

Antioxidants 2025, 14(7), 891; https://doi.org/10.3390/antiox14070891 - 20 Jul 2025

Abstract

Endothelial dysfunction contributes to the progression of metabolic-dysfunction-associated steatotic liver disease (MASLD). Pemafibrate has been shown to ameliorate MASLD in basic and clinical studies, but it is unclear whether it is also effective in the status of endothelial dysfunction. An MASLD animal model [...] Read more.

Endothelial dysfunction contributes to the progression of metabolic-dysfunction-associated steatotic liver disease (MASLD). Pemafibrate has been shown to ameliorate MASLD in basic and clinical studies, but it is unclear whether it is also effective in the status of endothelial dysfunction. An MASLD animal model was induced in male wild-type (WT) and endothelial nitric oxide synthase (eNOS)-deficient (eNOSKO) mice by feeding them a high-fat/cholesterol/cholate diet, and they were administered either a vehicle or pemafibrate at 0.17 mg/kg/day for 10 weeks. Although pemafibrate treatment did not change plasma lipid profiles in either WT or eNOSKO mice, pemafibrate reduced plasma AST levels in both WT and eNOSKO mice compared to the levels in the vehicle-treated mice. Histopathological analysis of the liver showed that MASLD was improved in the pemafibrate-treated groups in both WT and eNOSKO mice. Compared to vehicle treatment, pemafibrate treatment significantly reduced the expression levels of hepatic NADPH oxidase subunit genes, M1 macrophages, inflammatory-cytokine-related genes and profibrotic genes in both WT and eNOSKO mice, along with reduction in hepatic oxidative stress assessed by dihydroethidium staining and 4-hydroxynonenal protein levels. Thus, pemafibrate ameliorated MASLD with reduction in oxidative stress and inflammation even in vascular endothelial dysfunction. Full article

(This article belongs to the Special Issue Metabolic Dysfunction and Oxidative Stress)

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37 pages, 1761 KiB

Open AccessReview

Iron–Immune Crosstalk at the Maternal–Fetal Interface: Emerging Mechanisms in the Pathogenesis of Preeclampsia

by Jieyan Zhong, Ruhe Jiang, Nan Liu, Qingqing Cai, Qi Cao, Yan Du and Hongbo Zhao

Antioxidants 2025, 14(7), 890; https://doi.org/10.3390/antiox14070890 - 19 Jul 2025

Abstract

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder characterized by systemic inflammation, endothelial dysfunction, and placental insufficiency. While inadequate trophoblast invasion and impaired spiral artery remodeling have long been recognized as central to its pathogenesis, emerging evidence underscores the critical roles of dysregulated iron [...] Read more.

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder characterized by systemic inflammation, endothelial dysfunction, and placental insufficiency. While inadequate trophoblast invasion and impaired spiral artery remodeling have long been recognized as central to its pathogenesis, emerging evidence underscores the critical roles of dysregulated iron metabolism and its crosstalk with immune responses, particularly macrophage-mediated inflammation, in driving PE development. This review systematically explores the dynamic changes in iron metabolism during pregnancy, including increased maternal iron demand, placental iron transport mechanisms, and the molecular regulation of placental iron homeostasis. We further explore the contribution of ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, to trophoblast dysfunction and pregnancy-related diseases, including PE. Macrophages, pivotal immune regulators at the maternal–fetal interface, exhibit distinct polarization states that shape tissue remodeling and immune tolerance. We outline their origin, distribution, and polarization in pregnancy, and emphasize their aberrant phenotype and function in PE. The bidirectional crosstalk between iron and macrophages is also dissected: iron shapes macrophage polarization and function, while macrophages reciprocally modulate iron homeostasis. Notably, excessive reactive oxygen species (ROS) and pro-inflammatory cytokines secreted by M1-polarized macrophages may exacerbate trophoblast ferroptosis, amplifying placental injury. Within the context of PE, we delineate how iron overload and macrophage dysfunction synergize to potentiate placental inflammation and oxidative stress. Key iron-responsive immune pathways, such as the HO-1/hepcidin axis and IL-6/TNF-α signaling, are discussed in relation to disease severity. Finally, we highlight promising therapeutic strategies targeting the iron–immune axis, encompassing three key modalities—iron chelation therapy, precision immunomodulation, and metabolic reprogramming interventions—which may offer novel avenues for PE prevention and treatment. Full article

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26 pages, 1330 KiB

Open AccessReview

Cardioprotection Reloaded: Reflections on 40 Years of Research

by Pasquale Pagliaro, Giuseppe Alloatti and Claudia Penna

Antioxidants 2025, 14(7), 889; https://doi.org/10.3390/antiox14070889 - 18 Jul 2025

Abstract

Over the past four decades, cardioprotective research has revealed an extraordinary complexity of cellular and molecular mechanisms capable of mitigating ischemia/reperfusion injury (IRI). Among these, ischemic conditioning has emerged as one of the most influential discoveries: brief episodes of ischemia followed by reperfusion [...] Read more.

Over the past four decades, cardioprotective research has revealed an extraordinary complexity of cellular and molecular mechanisms capable of mitigating ischemia/reperfusion injury (IRI). Among these, ischemic conditioning has emerged as one of the most influential discoveries: brief episodes of ischemia followed by reperfusion activate protective programs that reduce myocardial damage. These effects can be elicited locally (pre- or postconditioning) or remotely (remote conditioning), acting mainly through paracrine signaling and mitochondria-linked kinase pathways, with both early and delayed windows of protection. We have contributed to clarifying the roles of mitochondria, oxidative stress, prosurvival kinases, connexins, extracellular vesicles, and sterile inflammation, particularly via activation of the NLRP3 inflammasome. Despite robust preclinical evidence, clinical translation of these approaches has remained disappointing. The challenges largely stem from experimental models that poorly reflect real-world clinical settings—such as advanced age, comorbidities, and multidrug therapy—as well as the reliance on surrogate endpoints that do not reliably predict clinical outcomes. Nevertheless, interest in multi-target protective strategies remains strong. New lines of investigation are focusing on emerging mediators—such as gasotransmitters, extracellular vesicles, and endogenous peptides—as well as targeted modulation of inflammatory responses. Future perspectives point toward personalized cardioprotection tailored to patient metabolic and immune profiles, with special attention to high-risk populations in whom IRI continues to represent a major clinical challenge. Full article

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12 pages, 1174 KiB

Open AccessArticle

The Influence of Diabetes Mellitus and Kidney Dysfunction on Oxidative Stress, a Reflection of the Multisystem Interactions in Aortic Stenosis

by Laura Mourino-Alvarez, Inés Perales-Sánchez, Germán Hernández-Fernández, Gabriel Blanco-López, Emilio Blanco-López, Rocío Eiros, Cristian Herrera-Flores, Miryam González-Cebrian, Teresa Tejerina, Jesús Piqueras-Flores, Pedro Luis Sánchez, Luis F. López-Almodóvar, Luis R. Padial and Maria G. Barderas

Antioxidants 2025, 14(7), 888; https://doi.org/10.3390/antiox14070888 - 18 Jul 2025

Abstract

Progression of aortic stenosis (AS) is aggravated by type 2 Diabetes Mellitus (T2DM) and kidney dysfunction (KD). Oxidative stress is one of the main mechanisms that triggers AS and is also disturbed among subjects with T2DM and KD. Consequently, we studied the redox [...] Read more.

Progression of aortic stenosis (AS) is aggravated by type 2 Diabetes Mellitus (T2DM) and kidney dysfunction (KD). Oxidative stress is one of the main mechanisms that triggers AS and is also disturbed among subjects with T2DM and KD. Consequently, we studied the redox homeostasis in four groups of patients, also classifying each patient based on their kidney function: control subjects, T2DM, AS, and AS+T2DM. Free reduced thiols in plasma were analyzed using a colorimetric assay, and the redox state of human serum albumin (HSA) was assessed by immunodetection and PEG-PCMal labeling. Lower levels of thiols were evident in patients with AS and AS+T2DM, while reduced and mildly oxidized HSA was more abundant in T2DM and AS+T2DM patients, reflecting less protection against oxidation. Moreover, the thiol levels decreased as KD increased in patients with AS and AS+T2DM. Differences also exist in reduced and mildly oxidized HSA between patients with normal and severely impaired kidney function, whereas AS patients with severe KD had more strongly oxidized HSA. Our results confirm an imbalance in oxidative stress associated with AS that is aggravated by the coexistence of T2DM and KD. Moreover, T2DM treatment might mitigate this dysfunction, opening the door to new therapeutic approaches for these patients. 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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20 pages, 2314 KiB

Open AccessArticle

Effects of 2-Hydroxypropyl-β-Cyclodextrin on the Antioxidant Efficiency of Some Gallic Acid Derivatives in Soybean Oil-in-Water Emulsions

by Tamara Martínez-Senra, Sonia Losada-Barreiro and Carlos Bravo-Díaz

Antioxidants 2025, 14(7), 887; https://doi.org/10.3390/antiox14070887 - 18 Jul 2025

Abstract

Cyclodextrins (CDs) have been widely employed as natural host molecules to form inclusion complexes with bioactive molecules such as antioxidants. Their particular spatial configuration, in the form of truncated cones formed through α(1–4) ether linkages of glucopyranose units, makes them very appropriate for [...] Read more.

Cyclodextrins (CDs) have been widely employed as natural host molecules to form inclusion complexes with bioactive molecules such as antioxidants. Their particular spatial configuration, in the form of truncated cones formed through α(1–4) ether linkages of glucopyranose units, makes them very appropriate for the formation of host–guest complexes, modifying their physicochemical properties and their location in multiphasic systems. Here, we investigated the effects of 2-hydroxypropyl-β-cyclodextrin (HPCD) on the efficiency of a series of gallic acid derivatives (propyl (PG), butyl (BG), octyl (OG), and lauryl (LG) gallates) in inhibiting the oxidation of soybean oil-in-water emulsions. For this purpose, we investigated the effects of HPCD on both the kinetics of lipid oxidation and the distribution of antioxidants in the same intact emulsions. The results show that in an aqueous solution, the antioxidants form 1:1 inclusion complexes with HPCD, with inclusion constants ranging from 383 M⁻¹ (PG) to 1946 M⁻¹ (OG). The results also show that the addition of HPCD to emulsions containing antioxidants does not lead to significant changes in their antioxidant effectiveness, with their efficiency being similar to that when no HPCD molecules are present. The results are interpreted in terms of the blocking effect exerted by the Tween 20 molecules, which act as effective guest competitors capable of removing the antioxidants from the HPCD cavity. The Tween 20 surfactant molecules need to be employed to stabilize the emulsions kinetically. This blocking effect, as a primary consequence, indicates that the interfacial concentration of the antioxidants, which is the region where the inhibition reaction takes place, remains constant; thus, their efficiency is not altered. Full article

(This article belongs to the Special Issue Antioxidants for the Oxidative Stabilisation of Food Lipids)

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21 pages, 3223 KiB

Open AccessArticle

Roles of 670 nm Photobiomodulation on Rat Anterior Ischemic Optic Neuropathy: Enhancing RGC Survival, Mitochondrial Function, and Anti-Inflammatory Response

by Tu-Wen Chen, Yao-Tseng Wen, Pei-Kang Liu, Monir Hossen and Rong-Kung Tsai

Antioxidants 2025, 14(7), 886; https://doi.org/10.3390/antiox14070886 - 18 Jul 2025

Abstract

Non-arteritic anterior ischemic optic neuropathy (NAION) leads to retinal ganglion cell (RGC) loss and visual impairment, with no effective treatment. This study investigated the neuroprotective effect of 670 nm photobiomodulation (PBM) in a rat NAION model (rNAION). Wistar rats received 670 nm light [...] Read more.

Non-arteritic anterior ischemic optic neuropathy (NAION) leads to retinal ganglion cell (RGC) loss and visual impairment, with no effective treatment. This study investigated the neuroprotective effect of 670 nm photobiomodulation (PBM) in a rat NAION model (rNAION). Wistar rats received 670 nm light exposure (10-min, 3000 lux) twice daily for 3 days after rAION injury, followed by 4 days of light treatment once a day. This study evaluated the neuroprotective effects of 670 nm light in an rNAION model. Rats received 670 nm light therapy (10 min/day, 3000 lux) for seven days post-injury. Treatment improved visual function (a 3.36-fold increase in FVEP amplitude), enhanced RGC survival (1.55-fold), and reduced apoptosis (a 15.86-fold reduction in TUNEL-positive cells). Inflammatory cytokines and ED1+ macrophage infiltration were significantly decreased. Oxidative stress was attenuated, with increased ATP, Nrf2, and PGC-1α levels and improved mitochondrial dynamics. These findings support 670 nm light as a potential therapy for NAION. 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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20 pages, 1903 KiB

Open AccessArticle

Study on the Regulatory Effect of Water Extract of Artemisia annua L. on Antioxidant Function of Mutton Sheep via the Keap1/Nrf2 Signaling Pathway

by Gen Gang, Ruiheng Gao, Ruizhen Li, Xiao Jin, Yuanyuan Xing, Sumei Yan, Yuanqing Xu and Binlin Shi

Antioxidants 2025, 14(7), 885; https://doi.org/10.3390/antiox14070885 - 18 Jul 2025

Abstract

This study was conducted through in vivo and in vitro experiments and aimed to reveal the regulatory effect of water extract of Artemisia annua L. (WEAA) on the antioxidant function of mutton sheep and the underlying mechanism. In the in vivo experiment, 32 [...] Read more.

This study was conducted through in vivo and in vitro experiments and aimed to reveal the regulatory effect of water extract of Artemisia annua L. (WEAA) on the antioxidant function of mutton sheep and the underlying mechanism. In the in vivo experiment, 32 Dorper × Han female sheep (3 months old; avg. body weight: 24 ± 0.09 kg) were allocated to four groups (eight lambs/group) and fed a diet containing 0, 500, 1000, and 1500 mg/kg WEAA, respectively. In the in vitro experiments, peripheral blood lymphocytes (PBLs) were cultured with different doses of WEAA (0, 25, 50, 100, 200, 400 µg/mL) to determine the optimal concentration, followed by a 2 × 2 factorial experiment with four treatment groups (six replicates per treatment group): the ML385(−)/WEAA(−) group, the ML385(−)/WEAA(+) group, the ML385(+)/WEAA(−) group, and the ML385(+)/WEAA(+) group. The results showed that WEAA supplementation dose-dependently increased serum, liver and spleen tissue total antioxidant capacity, glutathione peroxidase (GSH-Px), and catalase (CAT) activity while reducing malondialdehyde level (p < 0.05). Moreover, WEAA supplementation significantly upregulated the liver and spleen expression of nuclear factor erythroid 2-related factor 2, superoxide dismutase 2, GSH-Px, CAT and NAD(P)H quinone dehydrogenase 1 (p < 0.05) while significantly downregulating the kelch-like ECH associated protein 1 expression in a dose-dependent manner (p < 0.05), thereby activating the Keap1/Nrf2 pathway with the peak effect observed in the 1000 mg/kg WEAA group. Additionally, supplementation with 100 µg/mL of WEAA had significant antioxidation activity in the culture medium of PBLs. Its action mechanism involved the Keap1/Nrf2 pathway; specifically, WEAA exerted its antioxidant effect by upregulating the gene expression related to the Keap1/Nrf2 pathway. In conclusion, WEAA enhances sheep’s antioxidant capacity by up-regulating Keap1/Nrf2 pathway genes and boosting antioxidant enzyme activity. The results provided experimental support for the potential application of WEAA in intensive mutton sheep farming. Full article

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17 pages, 3083 KiB

Open AccessArticle

Antioxidant and Photoprotective Activities of Viola philippica Polyol Extracts

by Jiang Li, Jiancheng Ma, Ya Li, Lan Luo, Wenhuan Zhang, Yong Tian, Yuncai Tian, Yi Li, Zhongjuan Wang and Mingyi Wu

Antioxidants 2025, 14(7), 884; https://doi.org/10.3390/antiox14070884 - 18 Jul 2025

Abstract

Viola philippica (VP), a traditional Chinese medicinal herb widely used for its antibacterial and antioxidant properties, has recently garnered attention for its potential in skin photoprotection. VP was extracted using glycerol (GLY), 1,3-propanediol (PDO), and 1,3-butanediol (BDO) at concentrations of 30%, 60%, and [...] Read more.

Viola philippica (VP), a traditional Chinese medicinal herb widely used for its antibacterial and antioxidant properties, has recently garnered attention for its potential in skin photoprotection. VP was extracted using glycerol (GLY), 1,3-propanediol (PDO), and 1,3-butanediol (BDO) at concentrations of 30%, 60%, and 90% (w/w) to evaluate its antioxidant and UV-protective properties. The total phenolic content (TPC) and total flavonoid content (TFC) of the nine extracts ranged from 34.73 to 71.45 mg GAEs/g and from 26.68 to 46.68 mg REs/g, respectively, with the highest TPC observed in 90% PDO and the highest TFC in 60% GLY. Antioxidant assays revealed IC₅₀ values of 0.49–1.26 mg/mL (DPPH), 0.10–0.19 mg/mL (ABTS), and 1.58–460.95 mg/mL (OH). Notably, the 60% GLY, 30% PDO, and 90% PDO extracts demonstrated notable protective effects against UVB-induced cell damage, reducing intracellular ROS levels and preventing DNA damage. RNA-seq analysis revealed that the protective effects were associated with the modulation of key molecular pathways, including neutrophil extracellular trap formation and TNF, IL-17, and HIF-1 signaling. These findings suggest that Viola philippica polyol extracts, particularly those using 60% GLY, 30% PDO, and 90% PDO, have promising potential for skin photoprotection and could be utilized as natural antioxidants in cosmetic formulations. Full article

(This article belongs to the Special Issue Antioxidants for Skin Health)

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19 pages, 5092 KiB

Open AccessArticle

Salvianolic Acid B Alleviates LPS-Induced Spleen Injury by Remodeling Redox Status and Suppressing NLRP3 Inflammasome

by Hao Wang, Xiao Dou, Ruixue Wang, Yuxin Jiang, Jinsong Zhang, Xianjuan Qiao, Yingjun Liu, Hao Zhang, Chenhuan Lai, Yanan Chen and Qiang Yong

Antioxidants 2025, 14(7), 883; https://doi.org/10.3390/antiox14070883 - 18 Jul 2025

Abstract

Background: The spleen is the primary reservoir of immune cells in mammals. Diverse stimuli can disrupt spleen homeostasis, resulting in spleen injury and immune dysfunction. This study employed a porcine model to assess the therapeutic potential of salvianolic acid B (SAB) against [...] Read more.

Background: The spleen is the primary reservoir of immune cells in mammals. Diverse stimuli can disrupt spleen homeostasis, resulting in spleen injury and immune dysfunction. This study employed a porcine model to assess the therapeutic potential of salvianolic acid B (SAB) against lipopolysaccharide (LPS)-induced splenic injury. Methods: Seventy-two male weanling piglets were randomly assigned to one of four groups: CON-SS, SAB-SS, CON-LPS, and SAB-LPS. The CON-SS and CON-LPS groups received a basal diet, while SAB-SS and SAB-LPS groups received a SAB-supplemented diet. After 14 d, the CON-SS and SAB-SS groups received an intraperitoneal injection of sterile saline, whereas the CON-LPS and SAB-LPS groups were injected with LPS. Blood and spleen tissues were harvested 6 h post-injection for biochemical analysis. Results: LPS induced systemic immune disorders in piglets, as evidenced by increased immune organ indices and decreased white blood cell, lymphocyte, and basophil counts in blood (p < 0.05). LPS also caused histoarchitectural disruption, cell apoptosis, oxidative stress, and inflammation in the spleen (p < 0.05). Conversely, SAB improved splenic histopathology and reduced splenic apoptosis and pro-inflammatory mediators in piglets (p < 0.05). SAB significantly mitigated peroxidation accumulation by facilitating the nuclear translocation of nuclear factor erythroid 2-related factor 2 and strengthening the antioxidant system, and inhibited nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome activation (p < 0.05). Mechanistically, SAB attenuated LPS-induced splenic oxidative stress and NLRP3 inflammasome activation by restoring mitochondrial structure and function (p < 0.05). Conclusions: This research unveils that SAB alleviates LPS-induced spleen disorder by reinforcing antioxidant system and suppressing NLRP3 inflammasome, highlighting SAB’s potential as a prospective therapeutic agent for spleen disorders. Full article

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

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25 pages, 6270 KiB

Open AccessArticle

Ethanolic Extract of Glycine Semen Preparata Prevents Oxidative Stress-Induced Muscle Damage in C2C12 Cells and Alleviates Dexamethasone-Induced Muscle Atrophy and Weakness in Experimental Mice

by Aeyung Kim, Jinhee Kim, Chang-Seob Seo, Yu Ri Kim, Kwang Hoon Song and No Soo Kim

Antioxidants 2025, 14(7), 882; https://doi.org/10.3390/antiox14070882 - 18 Jul 2025

Abstract

Skeletal muscle atrophy is a debilitating condition characterized by the loss of muscle mass and function. It is commonly associated with aging, chronic diseases, disuse, and prolonged glucocorticoid therapy. Oxidative stress and catabolic signaling pathways play significant roles in the progression of muscle [...] Read more.

Skeletal muscle atrophy is a debilitating condition characterized by the loss of muscle mass and function. It is commonly associated with aging, chronic diseases, disuse, and prolonged glucocorticoid therapy. Oxidative stress and catabolic signaling pathways play significant roles in the progression of muscle degradation. Despite its clinical relevance, few effective therapeutic options are currently available. In this study, we investigated the protective effects of an ethanolic extract of Glycine Semen Preparata (GSP), i.e., fermented black soybeans, using in vitro and in vivo models of dexamethasone (Dexa)-induced muscle atrophy. In C2C12 myoblasts and myotubes, GSP significantly attenuated both oxidative stress-induced and Dexa-induced damages by reducing reactive oxygen species levels and by suppressing the expression of the muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin-1. Moreover, GSP upregulated key genes involved in muscle regeneration (Myod1 and Myog) and mitochondrial biogenesis (PGC1α), indicating its dual role in muscle protection and regeneration. Oral administration of GSP to mice with Dexa-induced muscle atrophy resulted in improved muscle fiber integrity, increased proportion of large cross-sectional area fibers, and partial recovery of motor function. Isoflavone aglycones, such as daidzein and genistein, were identified as active compounds that contribute to the beneficial effects of GSP through antioxidant activity and gene promoter enhancement. Thus, GSP is a promising nutraceutical that prevents or mitigates muscle atrophy by targeting oxidative stress and promoting myogenesis and mitochondrial function. Further studies are warranted to standardize the bioactive components and explore their clinical applications. Full article

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

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16 pages, 5315 KiB

Open AccessArticle

Guarana, Selenium, and L-Carnitine Supplementation Improves the Oxidative Profile but Fails to Reduce Tissue Damage in Rats with Osteoarthritis

by Aline Zuanazzi Pasinato, José Eduardo Vargas, Julia Spanhol da Silva, Joana Grandó Moretto, Cibele Ferreira Teixeira, Verônica Farina Azzolin, Ivana Beatrice Mânica da Cruz, Camile da Rosa Trevisan, Emanuele Cristina Zub, Renato Puga, Verónica Inés Vargas, Grethel León-Mejía and Rômulo Pillon Barcelos

Antioxidants 2025, 14(7), 881; https://doi.org/10.3390/antiox14070881 - 18 Jul 2025

Abstract

Osteoarthritis (OA) is a progressive joint disease that is commonly managed with palliative drugs, many of which are associated with undesirable side effects. This study investigated the therapeutic potential of a novel supplementation with guarana, selenium, and L-carnitine (GSC) in a rat model [...] Read more.

Osteoarthritis (OA) is a progressive joint disease that is commonly managed with palliative drugs, many of which are associated with undesirable side effects. This study investigated the therapeutic potential of a novel supplementation with guarana, selenium, and L-carnitine (GSC) in a rat model of chemically induced OA. Forty male Wistar rats (8–9 weeks old) received intra-articular sodium monoiodoacetate (Mia) to induce OA, and were subsequently treated with GSC. Inflammatory and oxidative stress parameters were analyzed at the end of the experiment. GSC supplementation enhanced endogenous antioxidant defenses, suggesting systemic antioxidant activity. However, no histological improvement was observed. In silico analyses indicated that Mia-induced OA may involve a complex molecular environment that GSC, at the tested dose, failed to modulate at the site of injury. Despite the limited local effects, these findings support the systemic benefits of GSC and highlight the potential of natural compound-based strategies in OA management. Given the adverse effects of conventional pharmacotherapy, the development of alternative, naturally derived treatments remains a promising avenue for future research. Full article

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

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23 pages, 2748 KiB

Open AccessArticle

Relationships Between H₂S and OT/OTR Systems in Preeclampsia

by Tamara Merz, Sarah Ecker, Nicole Denoix, Oscar McCook, Stefanie Kranz, Ulrich Wachter, Edit Rottler, Thomas Papadopoulos, Christoph Fusch, Cosima Brucker, Jakob Triebel, Thomas Bertsch, Peter Radermacher and Christiane Waller

Antioxidants 2025, 14(7), 880; https://doi.org/10.3390/antiox14070880 - 18 Jul 2025

Abstract

Pre-eclampsia (PE) is a hypertensive pregnancy complication. Oxidative stress is hypothesized to contribute to the pathophysiology of PE. Both the hydrogen sulfide (H₂S) and oxytocin (OT) systems might play a role in the pathophysiology of PE, like their antioxidant and hypotensive [...] Read more.

Pre-eclampsia (PE) is a hypertensive pregnancy complication. Oxidative stress is hypothesized to contribute to the pathophysiology of PE. Both the hydrogen sulfide (H₂S) and oxytocin (OT) systems might play a role in the pathophysiology of PE, like their antioxidant and hypotensive effects. Thus, the role of the interaction of the OT and H₂S systems in the context of PE was further elucidated in the present clinical case–control study “NU-HOPE” (Nürnberg-Ulm: The role of H₂S and Oxytocin Receptor in Pre-Eclampsia; ethical approval by the Landesärztekammer Bayern, file number 19033, 29 August 2019), comparing uncomplicated pregnancies, early onset PE (ePE, onset < 34 weeks gestational age) and late onset PE (lPE, onset > 34 weeks gestational age). Routine clinical data, serum H₂S and homocysteine levels, and tissue protein expression, as well as nitrotyrosine formation, were determined. The main findings were (i) unchanged plasma sulfide levels, (ii) significantly elevated homocysteine levels in ePE, but not lPE, (iii) significantly elevated expression of H₂S enzymes and OT receptor in the placenta in lPE, and (iv) significantly elevated nitrotyrosine formation in the lPE myometrium. Taken together, these findings suggest a role for the interaction of the endogenous H₂S- and OT/OTR systems in the pathophysiology of pre-eclampsia, possibly linked to impaired antioxidant protection. Full article

(This article belongs to the Special Issue Nitric Oxide (NO) and Hydrogen Sulfide (H₂S) in Biology, Illness, and Therapies—2nd Edition)

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25 pages, 4169 KiB

Open AccessArticle

In Vitro Effects of Rumex confertus Extracts on Cell Viability and Molecular Pathways in MCF-7 Breast Cancer Cells

by Levent Gülüm, Emrah Güler, Fatma Lale Aktaş, Ayşe Büşranur Çelik, Hilal Yılmaz and Yusuf Tutar

Antioxidants 2025, 14(7), 879; https://doi.org/10.3390/antiox14070879 - 18 Jul 2025

Abstract

Rumex confertus (RC), a plant known for its traditional medicinal uses, has shown potential anticancer properties, particularly due to its rich phenolic content. Despite its promising bioactivity, its effects on breast cancer cells remain underexplored. Here, we investigated the cytotoxic effects of RC [...] Read more.

Rumex confertus (RC), a plant known for its traditional medicinal uses, has shown potential anticancer properties, particularly due to its rich phenolic content. Despite its promising bioactivity, its effects on breast cancer cells remain underexplored. Here, we investigated the cytotoxic effects of RC extracts on MCF-7 breast cancer cells, employing various solvents for extraction. This study revealed that the hexane extract significantly reduced the cell viability, with an IC₅₀ of 9.40 µg/mL after 96 h. The gene expression analysis indicated a substantial modulation of transcriptional networks, including the upregulation of pluripotency-related genes and the downregulation of differentiation markers. The findings suggest that the RC extract may induce a shift towards a less differentiated, stem-like state in cancer cells, potentially enhancing malignancy resistance. This study underscores the potential of RC as a candidate for breast cancer treatment, and a further investigation into its therapeutic applications is suggested. Full article

(This article belongs to the Special Issue Anti-Cancer Potential of Plant-Based Antioxidants)

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18 pages, 2792 KiB

Open AccessArticle

Anti-Inflammatory Pathways Modulated by Microbial Polysaccharides from Euganean Thermal Muds in Zebrafish

by Micol Caichiolo, Raffaella Margherita Zampieri, Francesca Terrin, Annachiara Tesoriere, Fabrizio Caldara, Nicoletta La Rocca, Paolo Martini and Luisa Dalla Valle

Antioxidants 2025, 14(7), 878; https://doi.org/10.3390/antiox14070878 - 17 Jul 2025

Abstract

Thermal mud produced by spas of the Euganean Thermal District (Italy) has been used since ancient times for therapeutic purposes. Recently, the anti-inflammatory activity of microbial polysaccharides (M-PS), extracted from traditionally maturated muds, was demonstrated using the zebrafish model organism. However, the downstream [...] Read more.

Thermal mud produced by spas of the Euganean Thermal District (Italy) has been used since ancient times for therapeutic purposes. Recently, the anti-inflammatory activity of microbial polysaccharides (M-PS), extracted from traditionally maturated muds, was demonstrated using the zebrafish model organism. However, the downstream signalling pathways regulated by M-PS remain largely unknown. In this study, to investigate the underlying mechanisms of inflammation resolution, we performed a transcriptome analysis on zebrafish larvae inflamed with copper sulphate and treated with M-PS. Our findings revealed that M-PS treatment down-regulated the expression of key genes involved in several inflammatory pathways. Gene Set Enrichment Analysis identified eleven up-regulated pathways (e.g., TNF-α signalling via NFκB, IL6–JAK–STAT signalling, p53 pathway, apoptosis, and interferon response) with components reduced in number and expression level in M-PS-treated larvae compared to the inflamed ones. Additionally, seven down-regulated pathways were identified (e.g., transcription factors E2F, MYC, and the G2M checkpoint). DEG-pseudotime analysis further confirmed the association of these genes with the pathways identified by GSEA. These results provide valuable insights into the anti-inflammatory properties of M-PS and the therapeutic potential of Euganean thermal muds for inflammatory diseases. Full article

(This article belongs to the Special Issue Bioactive Compounds: Antioxidant, Antibacterial, Anti-inflammatory Modulation)

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37 pages, 911 KiB

Open AccessReview

Expression of Free Radicals and Reactive Oxygen Species in Endometriosis: Current Knowledge and Its Implications

by Jeongmin Lee, Seung Geun Yeo, Jae Min Lee, Sung Soo Kim, Jin-Woo Lee, Namhyun Chung and Dong Choon Park

Antioxidants 2025, 14(7), 877; https://doi.org/10.3390/antiox14070877 - 17 Jul 2025

Abstract

This review explores the dual role of reactive oxygen species (ROS) and free radicals in the pathogenesis of endometriosis, aiming to deepen our understanding of these processes through a systematic literature review. To assess the induction and involvement of ROS in endometriosis, we [...] Read more.

This review explores the dual role of reactive oxygen species (ROS) and free radicals in the pathogenesis of endometriosis, aiming to deepen our understanding of these processes through a systematic literature review. To assess the induction and involvement of ROS in endometriosis, we conducted a comprehensive literature review using Cochrane Libraries, EMBASE, Google Scholar, PubMed, and SCOPUS databases. Of 30 qualifying papers ultimately reviewed, 28 reported a significant contribution of ROS to the pathogenesis of endometriosis, while two found no association. The presence of ROS in endometriosis is associated with infertility, irregular menstrual cycles, painful menstruation, and chronic pelvic discomfort. Among individual ROS types studied, hydrogen peroxide was most frequently investigated, followed by lipid peroxides and superoxide radicals. Notable polymorphisms associated with ROS in endometriosis include those for AT-rich interactive domain 1A (ARID1A) and quinone oxidoreductase 1 (NQO1) isoforms. Key enzymes for ROS scavenging and detoxification include superoxide dismutase, glutathione, and glutathione peroxidase. Effective inhibitors of ROS related to endometriosis are vitamins C and E, astaxanthin, fatty acid-binding protein 4, cerium oxide nanoparticles (nanoceria), osteopontin, sphingosine 1-phosphate, N-acetyl-L-cysteine, catalase, and a high-antioxidant diet. Elevated levels of ROS and free radicals are involved in the pathogenesis of endometriosis, suggesting that targeting these molecules could offer potential therapeutic strategies. Full article

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15 pages, 1866 KiB

Open AccessArticle

A High-Fat Diet Induces Oxidative Stress in OPA1^+/− Mouse Cortices: A Critical Double Challenge

by Camille Champigny, Marlène Botella, Djamaa Atamena, Sébastien Bullich, Corentin Coustham, Bruno Guiard, Pascale Belenguer and Noélie Davezac

Antioxidants 2025, 14(7), 876; https://doi.org/10.3390/antiox14070876 - 17 Jul 2025

Abstract

A high-fat diet (HFD) has significant effects on health, leading to cardiovascular, metabolic, neurodegenerative, and psychiatric conditions and contributing to obesity and type 2 diabetes. Mitochondria, essential for energy production and oxidative metabolism, are adversely affected by a HFD, causing oxidative stress and [...] Read more.

A high-fat diet (HFD) has significant effects on health, leading to cardiovascular, metabolic, neurodegenerative, and psychiatric conditions and contributing to obesity and type 2 diabetes. Mitochondria, essential for energy production and oxidative metabolism, are adversely affected by a HFD, causing oxidative stress and impaired cellular function. Mutations in the OPA1 (OPtic Atrophy 1) gene, crucial for mitochondrial dynamics and functions, are responsible for dominant optic atrophy (DOA), a mitochondrial neurodegenerative disease associated with increased reactive oxygen species (ROS). The expressivity of DOA is highly variable, even within the same family. This suggests that both modifying genetics and environmental factors could influence the penetrance of the disease. We previously demonstrated that genetic background modulates DOA expressivity and now ask if this is also the case for external cues. We thus explore how OPA1 deficiency interacts with HFD-induced metabolic disturbances, hypothesizing that long-term HFD consumption impairs brain mitochondrial function and disrupts oxidative metabolism. OPA1^+/− mice were thus subjected to a HFD for a period of 12 weeks, and ROS levels and the expression of antioxidant genes were evaluated by Western blot and spectrophotometry. Cortices from high-fat diet-fed OPA1^+/− mice showed lower aconitase activity than those of their wild-type (WT) litter mates, indicative of an unbalanced increase in mitochondrial ROS. Accordingly, OPA1^+/− mice present lower levels of the antioxidant enzyme superoxide dismutase 2 compared to WT mice. Therefore, this study (i) reveals the onset of oxidative stress in brain cortices from OPA1^+/− mice challenged with a HFD, (ii) shows that diet is a modifying factor for DOA, and (iii) suggests that food control could be used to moderate the severity of the disease. Full article

(This article belongs to the Special Issue Redox Signaling in Brain Aging and Neurodegeneration)

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