Antioxidants

18 pages, 3660 KiB

Open AccessArticle

Massa Medicata Fermentata, a Functional Food for Improving the Metabolic Profile via Prominent Anti-Oxidative and Anti-Inflammatory Effects

by Kyung-Mi Jung, Ga-Ram Yu, Da-Hoon Kim, Dong-Woo Lim and Won-Hwan Park

Antioxidants 2024, 13(10), 1271; https://doi.org/10.3390/antiox13101271 (registering DOI) - 19 Oct 2024

Abstract

Massa Medicata Fermentata (MMF) is a naturally fermented product used to treat indigestion and increase stomach activity in traditional medicine. This study examined the ability of the hydrothermal extract of MMF to scavenge free radicals corresponding to biological oxidative stresses, further protecting essential [...] Read more.

Massa Medicata Fermentata (MMF) is a naturally fermented product used to treat indigestion and increase stomach activity in traditional medicine. This study examined the ability of the hydrothermal extract of MMF to scavenge free radicals corresponding to biological oxidative stresses, further protecting essential biomolecules. The anti-inflammatory effects of MMF were evaluated in LPS-induced RAW264.7 macrophages and zebrafish. In addition, the effects of MMF on the body mass index (BMI) and cholesterol accumulation in adult zebrafish fed a high-cholesterol diet (HCD) for three weeks were examined. MMF prevented the DNA and lipid damage caused by oxidative stress, inhibited LDL oxidation, and reduced the expression of cytokines and related proteins (MAPK and NFκB), with prominent anti-oxidative pathway (NRF2-HO-1) activation properties. LPS-induced NO production was reduced, and the increase in BMI and TC caused by the HCD diet was suppressed by MMF in zebrafish embryos or adult zebrafish. The bioactive aglycone of quercetin may be contributing to the mechanisms of systemic effects. MMF has excellent antioxidant properties and is useful for improving inflammation status and metabolic profile, thus highlighting its potential as a healthy, functional food. Full article

(This article belongs to the Special Issue Natural Bioactive Compounds Exerting Health Promoting Effects through Ameliorating Oxidative Stress)

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21 pages, 5821 KiB

Open AccessReview

Modulation of NRF2/KEAP1 Signaling by Phytotherapeutics in Periodontitis

by Giovanni Tossetta, Sonia Fantone, Lucrezia Togni, Andrea Santarelli, Fabiola Olivieri, Daniela Marzioni and Maria Rita Rippo

Antioxidants 2024, 13(10), 1270; https://doi.org/10.3390/antiox13101270 (registering DOI) - 18 Oct 2024

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Abstract

Periodontitis affects up to 40% of adults over 60 years old and is a consequence of gingivitis. Periodontitis is characterized by a chronic inflammation, periodontal damage, and alveolar bone resorption. The nuclear factor erythroid 2-related factor 2 (NFE2L2 or NRF2)/Kelch-like ECH-Associated Protein 1 [...] Read more.

Periodontitis affects up to 40% of adults over 60 years old and is a consequence of gingivitis. Periodontitis is characterized by a chronic inflammation, periodontal damage, and alveolar bone resorption. The nuclear factor erythroid 2-related factor 2 (NFE2L2 or NRF2)/Kelch-like ECH-Associated Protein 1 (KEAP1) (NRF2/KEAP1) signaling pathway plays a key role in periodontitis by modulating redox balance and inflammation of the periodontium. However, NRF2 expression is decreased in gingival tissues of patients with periodontitis while oxidative stress is significantly increased in this pathology. Oxidative stress and lipopolysaccharide (LPS) produced by gram-negative bacteria favor the production of inflammatory causing periodontal inflammation and favoring alveolar bone. In this review, we analyzed the current literature regarding the role of natural and synthetic compounds in modulating the NRF2/KEAP1 pathway in in vitro and in vivo models of periodontitis in order to evaluate new potential treatments of periodontitis that can improve the outcome of this disease. Full article

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17 pages, 2874 KiB

Open AccessArticle

Astaxanthin Supplementation Effects in Right Ventricle of Rats Exposed to Chronic Intermittent Hypobaric Hypoxia

by Eduardo Pena, Samia El Alam, Constanza Gonzalez, Isaac Cortés, Diego Aguilera, Karen Flores and Karem Arriaza

Antioxidants 2024, 13(10), 1269; https://doi.org/10.3390/antiox13101269 (registering DOI) - 18 Oct 2024

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Abstract

In Chile, individuals are commonly exposed to high altitude due to the work shift system, involving days of exposure to high altitude followed by days at sea level over the long term, which can result in chronic intermittent hypobaric hypoxia (CIHH). CIHH can [...] Read more.

In Chile, individuals are commonly exposed to high altitude due to the work shift system, involving days of exposure to high altitude followed by days at sea level over the long term, which can result in chronic intermittent hypobaric hypoxia (CIHH). CIHH can cause high-altitude pulmonary hypertension (HAPH), the principal manifestation of which is right ventricular hypertrophy (RVH), in some cases leading to heart failure and eventually death. Studies have shown the contribution of oxidative stress and inflammation to RVH development. Recently, it was determined that the pigment astaxanthin has high antioxidant capacity and strong anti-inflammatory and cardioprotective effects. Therefore, the aim of this study was to determine the effects of astaxanthin on RVH development in rats subjected to CIHH. Methods: Thirty two male Wistar rats were randomly assigned to the following groups (n = 8 per group): the normoxia with vehicle (NX), normoxia with astaxanthin (NX + AS), chronic intermittent hypobaric hypoxia with vehicle (CIHH), and chronic intermittent hypobaric hypoxia with astaxanthin (CIHH + AS) groups. CIHH was simulated by 2 days in a hypobaric chamber followed by 2 days at sea level for 29 days. Results: Exposure to CIHH induced RVH and increased lipid peroxidation (MDA), Nox2 expression, and SOD activity, however, it decreased pro-IL-1β expression. Astaxanthin restored oxidative stress markers (Nox2 and MDA), increased GPx activity, and decreased RVH compared to CIHH. Conclusion: Astaxanthin alleviates RVH and reduces Nox2 and MDA levels while increasing GPx activity in rats subjected to CIHH. These findings provide new insights of astaxanthin as a new nutraceutical against high-altitude effects. Full article

(This article belongs to the Special Issue Innovative Therapeutic Approaches for Hypertension and Cardiovascular Diseases: Targeting Oxidative Stress Pathways)

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18 pages, 6935 KiB

Open AccessArticle

Microplastic-Enhanced Cadmium Toxicity: A Growing Threat to the Sea Grape, Caulerpa lentillifera

by Weilong Zhou, Haolong Zheng, Yingyin Wu, Junyi Lin, Xiaofei Ma, Yixuan Xing, Huilong Ou, Hebert Ely Vasquez, Xing Zheng, Feng Yu and Zhifeng Gu

Antioxidants 2024, 13(10), 1268; https://doi.org/10.3390/antiox13101268 (registering DOI) - 18 Oct 2024

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Abstract

The escalating impact of human activities has led to the accumulation of microplastics (MPs) and heavy metals in marine environments, posing serious threats to marine ecosystems. As essential components of oceanic ecosystems, large seaweeds such as Caulerpa lentillifera play a crucial role in [...] Read more.

The escalating impact of human activities has led to the accumulation of microplastics (MPs) and heavy metals in marine environments, posing serious threats to marine ecosystems. As essential components of oceanic ecosystems, large seaweeds such as Caulerpa lentillifera play a crucial role in maintaining ecological balance. This study investigated the effects of MPs and cadmium (Cd) on the growth, physiology, biochemistry, and Cd accumulation in C. lentillifera while elucidating the underlying molecular regulatory mechanisms. The results demonstrated that exposure to MPs alone significantly promoted the growth. In contrast, exposure to Cd either alone or in combination with MPs significantly suppressed growth by reducing stem and stolon length, bud count, weight gain, and specific growth rates. Combined exposure to MPs and Cd exhibited the most pronounced inhibitory effect on growth. MPs had negligible impact while Cd exposure either alone or combined with MPs impaired antioxidant defenses and exacerbated oxidative damage; with combined exposure being the most detrimental. Analysis of Cd content revealed that MPs significantly increased Cd accumulation in algae intensifying its toxic effects. Gene expression analysis revealed that Cd exposure down-regulated key genes involved in photosynthesis, impairing both photosynthetic efficiency and energy conversion. The combined exposure of MPs and Cd further exacerbated these effects. In contrast, MPs alone activated the ribosome pathway, supporting ribosomal stability and protein synthesis. Additionally, both Cd exposure alone or in combination with MPs significantly reduced chlorophyll B and soluble sugar content, negatively impacting photosynthesis and nutrient accumulation. In summary, low concentrations of MPs promoted C. lentillifera growth, but the presence of Cd hindered it by disrupting photosynthesis and antioxidant mechanisms. Furthermore, the coexistence of MPs intensified the toxic effects of Cd. These findings enhance our understanding of how both MPs and Cd impact large seaweed ecosystems and provide crucial insights for assessing their ecological risks. Full article

(This article belongs to the Special Issue The Role of Oxidative Stress in Aquaculture)

32 pages, 10079 KiB

Open AccessArticle

Deciphering the Landscape of GATA-Mediated Transcriptional Regulation in Gastric Cancer

by Rodiola Begolli, Anastasia Patouna, Periklis Vardakas, Anastasia Xagara, Kleanthi Apostolou, Demetrios Kouretas and Antonis Giakountis

Antioxidants 2024, 13(10), 1267; https://doi.org/10.3390/antiox13101267 - 18 Oct 2024

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Abstract

Gastric cancer (GC) is an asymptomatic malignancy in early stages, with an invasive and cost-ineffective diagnostic toolbox that contributes to severe global mortality rates on an annual basis. Ectopic expression of the lineage survival transcription factors (LS-TFs) GATA4 and 6 promotes stomach oncogenesis. [...] Read more.

Gastric cancer (GC) is an asymptomatic malignancy in early stages, with an invasive and cost-ineffective diagnostic toolbox that contributes to severe global mortality rates on an annual basis. Ectopic expression of the lineage survival transcription factors (LS-TFs) GATA4 and 6 promotes stomach oncogenesis. However, LS-TFs also govern important physiological roles, hindering their direct therapeutic targeting. Therefore, their downstream target genes are particularly interesting for developing cancer-specific molecular biomarkers or therapeutic agents. In this work, we couple inducible knockdown systems with chromatin immunoprecipitation and RNA-seq to thoroughly detect and characterize direct targets of GATA-mediated transcriptional regulation in gastric cancer cells. Our experimental and computational strategy provides evidence that both factors regulate the expression of several coding and non-coding RNAs that in turn mediate for their cancer-promoting phenotypes, including but not limited to cell cycle, apoptosis, ferroptosis, and oxidative stress response. Finally, the diagnostic and prognostic potential of four metagene signatures consisting of selected GATA4/6 target transcripts is evaluated in a multi-cancer panel of ~7000 biopsies from nineteen tumor types, revealing elevated specificity for gastrointestinal tumors. In conclusion, our integrated strategy uncovers the landscape of GATA-mediated coding and non-coding transcriptional regulation, providing insights regarding their molecular and clinical function in gastric cancer. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Carcinogenesis: A Multifaceted Approach)

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15 pages, 2636 KiB

Open AccessArticle

Radical Scavenging Capacity and In Vitro Cytoprotective Effects of Great Salt Lake-Derived Processed Mineral Water

by Takayuki Mokudai, Seiko Nakagawa, Hiroyasu Kanetaka, Kazuo Oda, Hiroya Abe and Yoshimi Niwano

Antioxidants 2024, 13(10), 1266; https://doi.org/10.3390/antiox13101266 - 18 Oct 2024

Viewed by 189

Abstract

The Great Salt Lake, located in Utah, USA, is a saltwater lake with no outlet and is surrounded by vast mountains and salt deserts. We aimed to use Great Salt Lake-derived processed mineral water (hereafter termed as GSL-MW) for maintaining oral health. Therefore, [...] Read more.

The Great Salt Lake, located in Utah, USA, is a saltwater lake with no outlet and is surrounded by vast mountains and salt deserts. We aimed to use Great Salt Lake-derived processed mineral water (hereafter termed as GSL-MW) for maintaining oral health. Therefore, we examined its radical scavenging activity as an antioxidant and its cytoprotective effect on human gingival fibroblasts (hGFs). The scavenging activity against O₂^•− radicals was determined by an electron spin resonance (ESR)-spin trapping technique using two kinds of O₂^•− generation systems; however, we could not reach any concrete conclusion because of the interference caused by GSL-MW in both systems. Detection of ·OH radicals using the ESR-spin trapping technique and kinetic analyses using double-reciprocal plots (corresponding to Lineweaver–Burk plots that are used to represent enzyme kinetics) revealed that GSL-MW has the ability to scavenge ·OH radicals. GSL-MW also showed a weak 2,2-diphenyl-1-picrylhydrazyl (DPPH; a stable radical)-scavenging activity. Regarding the cytoprotective effects, subconfluent hGFs pretreated with 10× and 100× dilutions of GSL-MW for 3 min and then exposed to harsh environmental conditions, such as pure water or 100 μM H₂O₂ for 3 min, showed enhanced cell viability rate. Moreover, 10× and 100× dilutions of GSL-MW reduced oxidative damage in confluent hGFs exposed to 12.5 and 25 mM H₂O₂. Our findings show that GSL-MW has antioxidant potential and cytoprotective effects on hGFs, suggesting that GSL-MW can be used to maintain oral health. Full article

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

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24 pages, 5596 KiB

Open AccessArticle

Rosmarinic Acid Attenuates Salmonella enteritidis-Induced Inflammation via Regulating TLR9/NF-κB Signaling Pathway and Intestinal Microbiota

by Dandan Yi, Menghui Wang, Xia Liu, Lanqian Qin, Yu Liu, Linyi Zhao, Ying Peng, Zhengmin Liang and Jiakang He

Antioxidants 2024, 13(10), 1265; https://doi.org/10.3390/antiox13101265 - 18 Oct 2024

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Abstract

Salmonella enteritidis (SE) infection disrupts the homeostasis of the intestinal microbiota, causing an intestinal inflammatory response and posing a great threat to human and animal health. The unreasonable use of antibiotics has led to an increase in the prevalence of drug-resistant [...] Read more.

Salmonella enteritidis (SE) infection disrupts the homeostasis of the intestinal microbiota, causing an intestinal inflammatory response and posing a great threat to human and animal health. The unreasonable use of antibiotics has led to an increase in the prevalence of drug-resistant SE, increasing the difficulty of controlling SE. Therefore, new drug strategies and research are urgently needed to control SE. Rosmarinic acid (RA) is a natural phenolic acid with various pharmacological activities, including antioxidant, anti-inflammatory and antibacterial properties. However, the protective effects and mechanism of RA on intestinal inflammation and the gut microbial disorders caused by SE have not been fully elucidated. In this study, RAW264.7 cells, MCECs and BALB/c mice were challenged with SE to assess the protective effects and mechanisms of RA. The results showed that RA enhanced the phagocytic ability of RAW264.7 cells, reduced the invasion and adhesion ability of SE in MCECs, and inhibited SE-induced inflammation in cells. Moreover, RA inhibited the activation of the NF-κB signaling pathway by upregulating TLR9 expression. Importantly, we found that RA provided protection against SE and increased the diversity and abundance of the intestinal microbiota in mice. Compared with infection control, RA significantly increased the abundance of Firmicutes and Acidibacteria and decreased the abundance of Proteobacteria, Epsilonbacteraeota and Bacteroidota. However, RA failed to alleviate SE-induced inflammation and lost its regulatory effects on the TLR9/NF-κB signaling pathway after destroying the gut microbiota with broad-spectrum antibiotics. These results indicated that RA attenuated SE-induced inflammation by regulating the TLR9/NF-κB signaling pathway and maintaining the homeostasis of the gut microbiota. Our study provides a new strategy for preventing SE-induced intestinal inflammation. Full article

(This article belongs to the Topic Recent Advances in Veterinary Pharmacology and Toxicology)

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13 pages, 1986 KiB

Open AccessPerspective

Antioxidants: A Hot Controversy Defused by Cool Semantics

by Ahmad Yaman Abdin, Muhammad Jawad Nasim and Claus Jacob

Antioxidants 2024, 13(10), 1264; https://doi.org/10.3390/antiox13101264 - 18 Oct 2024

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Abstract

Recent years have witnessed a rather controversial debate on what antioxidants are and how beneficial they may be in the context of human health. Despite a considerable increase in scientific evidence, the matter remains highly divisive as different pieces of new data seem [...] Read more.

Recent years have witnessed a rather controversial debate on what antioxidants are and how beneficial they may be in the context of human health. Despite a considerable increase in scientific evidence, the matter remains highly divisive as different pieces of new data seem to support both the pro- and the anti-antioxidant perspective. Here, we argue that the matter at the heart of this debate is not necessarily empirical but of semantics. Thus, the controversy cannot be resolved with the traditional tools of natural sciences and by the mere accumulation of new data. In fact, the term “antioxidants” has been part of the scientific language game for a few decades and is nowadays used differently in the context of different scientific disciplines active at different levels of scientific complexity. It, therefore, represents not a single expression but an entire family of words with distinctively different connotations and associations. The transcendent use of this expression from a basic to a more complex discipline, such as going from chemistry to physiology, is problematic as it assigns the term with connotations that are not corroborated empirically. This may lead to false claims and aspirations not warranted by empirical data. Initially, health claims may not even be indented, yet, on occasion, they are welcome for reasons other than scientific ones. To resolve this debate, one may need to refrain from using the term “antioxidants” in disciplines and contexts where its meaning is unclear, limit its use to disciplines where it is essential and beneficial, and, in any case, become more specific in such contexts where its use is warranted, for instance, in the case of “dietary antioxidants”. Full article

(This article belongs to the Special Issue Something is Rotten in the State of Redox)

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18 pages, 2532 KiB

Open AccessArticle

Role of Callistemon citrinus Leaf Phytosomes Against Oxidative Stress and Inflammation in Rats Fed with a High-Fat-Fructose Diet

by Luis Gerardo Ortega-Pérez, José Armando Hernández-Soto, Osvaldo Padilla-Avalos, Luis Alberto Ayala-Ruiz, Oliver Rafid Magaña-Rodríguez, Jonathan Saúl Piñón-Simental, Asdrúbal Aguilera-Méndez, Daniel Godínez-Hernández and Patricia Rios-Chavez

Antioxidants 2024, 13(10), 1263; https://doi.org/10.3390/antiox13101263 - 18 Oct 2024

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Abstract

Phytosomes are used as vehicles that carry plant extracts. They exhibit biological activities and possess better bioavailability, bioabsorption, and lower toxicity than drugs. Obesity is an inflammatory state in which oxidative stress is present, which triggers severe effects on the body’s organs. This [...] Read more.

Phytosomes are used as vehicles that carry plant extracts. They exhibit biological activities and possess better bioavailability, bioabsorption, and lower toxicity than drugs. Obesity is an inflammatory state in which oxidative stress is present, which triggers severe effects on the body’s organs. This study aimed to evaluate the impact of the extract and phytosomes of Callistemon citrinus on oxidative stress and inflammation in the liver and heart of Wistar rats fed with a high-fat-fructose diet. Phytosomes containing the extract of leaves of C. citrinus were prepared. The antioxidant, pro-inflammatory enzymes, and biomarkers of oxidative stress were evaluated. Among the groups, only the high-fat-fructose group presented an increase in the COX-2, 5-LOX, and MPO inflammatory enzymes, while the XO enzyme exhibited decreased activity. The groups were fed a hypercaloric diet for 15 weeks while orlistat, C. citrinus extract, and phytosomes were administered at three different concentrations, exhibiting enzyme activities similar to those of the control group. It was also observed that the lowest concentration of phytosomes had a comparable effect to the other concentrations. Callistemon citrinus extract can modulate the activities of enzymes involved in the inflammation process. Furthermore, small doses of phytosomes can serve as anti-inflammatory agents. Full article

(This article belongs to the Special Issue Antioxidant and Antimicrobial Activity of Plant Extracts and Their Pharmacological Applications)

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2 pages, 417 KiB

Open AccessCorrection

Correction: Xu et al. Use of Optical Redox Imaging to Quantify Alveolar Macrophage Redox State in Infants: Proof of Concept Experiments in a Murine Model and Human Tracheal Aspirates Samples. Antioxidants 2024, 13, 546

by He N. Xu, Diego Gonzalves, Jonathan H. Hoffman, Joseph A. Baur, Lin Z. Li and Erik A. Jensen

Antioxidants 2024, 13(10), 1262; https://doi.org/10.3390/antiox13101262 - 18 Oct 2024

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Abstract

In the original publication [...] Full article

5 pages, 200 KiB

Open AccessEditorial

The Ubiquitous and Multifaceted Coenzyme Q

by Luca Tiano and Plácido Navas

Antioxidants 2024, 13(10), 1261; https://doi.org/10.3390/antiox13101261 - 17 Oct 2024

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Abstract

Coenzyme Q₁₀ (CoQ₁₀) is composed of a benzoquinone ring and an isoprenoid side chain attached to carbon 3 of the ring [...] Full article

(This article belongs to the Special Issue The Ubiquitous and Multifaceted Coenzyme Q)

16 pages, 2885 KiB

Open AccessArticle

Association Between NOX2-Mediated Oxidative Stress, Low-Grade Endotoxemia, Hypoalbuminemia, and Clotting Activation in COVID-19

by Roberto Carnevale, Cristina Nocella, Raffaella Marocco, Paola Zuccalà, Anna Carraro, Vittorio Picchio, Alessandra Oliva, Roberto Cangemi, Maria Claudia Miele, Massimiliano De Angelis, Francesca Cancelli, Giovanni Enrico Casciaro, Luca Cristiano, Pasquale Pignatelli, Giacomo Frati, Mario Venditti, Francesco Pugliese, Claudio Maria Mastroianni, Francesco Violi, Lorenzo Ridola, Cosmo Del Borgo, Silvia Palmerio, Emiliano Valenzi, Rita Carnevale, Domenico Alvaro, Miriam Lichtner and Vincenzo Cardinale Show full author list Hide full author list

Antioxidants 2024, 13(10), 1260; https://doi.org/10.3390/antiox13101260 - 17 Oct 2024

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Abstract

Low-grade endotoxemia by lipopolysaccharide (LPS) has been detected in COVID-19 and could favor thrombosis via eliciting a pro-inflammatory and pro-coagulant state. The aim of this study was to analyze the mechanism accounting for low-grade endotoxemia and its relationship with oxidative stress and clotting [...] Read more.

Low-grade endotoxemia by lipopolysaccharide (LPS) has been detected in COVID-19 and could favor thrombosis via eliciting a pro-inflammatory and pro-coagulant state. The aim of this study was to analyze the mechanism accounting for low-grade endotoxemia and its relationship with oxidative stress and clotting activation thrombosis in COVID-19. We measured serum levels of sNOX2-dp, zonulin, LPS, D-dimer, and albumin in 175 patients with COVID-19, classified as having or not acute respiratory distress syndrome (ARDS), and 50 healthy subjects. Baseline levels of sNOX2-dp, LPS, zonulin, D-dimer, albumin, and hs-CRP were significantly higher in COVID-19 compared to controls. In COVID-19 patients with ARDS, sNOX2-dp, LPS, zonulin, D-dimer, and hs-CRP were significantly higher compared to COVID-19 patients without ARDS. Conversely, concentration of albumin was lower in patients with ARDS compared with those without ARDS and inversely associated with LPS. In the COVID-19 cohort, the number of patients with ARDS progressively increased according to sNOX2-dp and LPS quartiles; a significant correlation between LPS and sNOX2-dp and LPS and D-dimer was detected in COVID-19. In a multivariable logistic regression model, LPS/albumin levels and D-dimer predicted thrombotic events. In COVID-19 patients, LPS is significantly associated with a hypercoagulation state and disease severity. In vitro, LPS can increase endothelial oxidative stress and coagulation biomarkers that were reduced by the treatment with albumin. In conclusion, impaired gut barrier permeability, increased NOX2 activation, and low serum albumin may account for low-grade endotoxemia and may be implicated in thrombotic events in COVID-19. Full article

(This article belongs to the Special Issue Roles of NADPH Oxidase in Modulation of Signal Transduction and Cellular Metabolism—2nd Edition)

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19 pages, 6139 KiB

Open AccessArticle

Solid-State Fermentation of Wheat Bran with Clostridium butyricum: Impact on Microstructure, Nutrient Release, Antioxidant Capacity, and Alleviation of Ulcerative Colitis in Mice

by Heng Zhang, Min Zhang, Xin Zheng, Xiaofang Xu, Jiawen Zheng, Yuanliang Hu, Yuxia Mei, Yangyang Liu and Yunxiang Liang

Antioxidants 2024, 13(10), 1259; https://doi.org/10.3390/antiox13101259 - 17 Oct 2024

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Abstract

This study investigated the effects of solid-state fermentation with Clostridium butyricum on the microstructure of wheat bran, the release of dietary fiber and phenolic compounds, and antioxidant capacity. Compared with unfermented wheat bran, insoluble dietary fiber and phytic acid content decreased, whereas soluble [...] Read more.

This study investigated the effects of solid-state fermentation with Clostridium butyricum on the microstructure of wheat bran, the release of dietary fiber and phenolic compounds, and antioxidant capacity. Compared with unfermented wheat bran, insoluble dietary fiber and phytic acid content decreased, whereas soluble dietary fiber and water-extractable arabinoxylan content increased in C. butyricum culture. Because of the increased release of phenolic compounds, such as ferulic acid and apigenin, and organic acids, such as isobutyric acid, the antioxidant capacity of the culture was considerably improved. Furthermore, the culture of C. butyricum treated with dextran sulfate sodium-induced ulcerative colitis in mice enhanced the expression of intestinal mucus and tight-junction proteins, modulating the gut microbiota structure, increasing the levels of short-chain fatty acids in the intestine, and restoring the essential functions of the gut microbiota. These anti-inflammatory effects stemmed from the combined action of various effective components. Full article

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14 pages, 2818 KiB

Open AccessArticle

α-Terpineol Induces Shelterin Components TRF1 and TRF2 to Mitigate Senescence and Telomere Integrity Loss via A Telomerase-Independent Pathway

by Marianna Kapetanou, Sophia Athanasopoulou, Andreas Goutas, Dimitra Makatsori, Varvara Trachana and Efstathios Gonos

Antioxidants 2024, 13(10), 1258; https://doi.org/10.3390/antiox13101258 - 17 Oct 2024

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Abstract

Cellular senescence is a hallmark of aging characterized by irreversible growth arrest and functional decline. Progressive telomeric DNA shortening in dividing somatic cells, programmed during development, leads to critically short telomeres that trigger replicative senescence and thereby contribute to aging. Therefore, protecting telomeres [...] Read more.

Cellular senescence is a hallmark of aging characterized by irreversible growth arrest and functional decline. Progressive telomeric DNA shortening in dividing somatic cells, programmed during development, leads to critically short telomeres that trigger replicative senescence and thereby contribute to aging. Therefore, protecting telomeres from DNA damage is essential in order to avoid entry into senescence and organismal aging. In several organisms, including mammals, telomeres are protected by a protein complex named shelterin that prevents DNA damage at the chromosome ends through the specific function of its subunits. Here, we reveal that the nuclear protein levels of shelterin components TRF1 and TRF2 decline in fibroblasts reaching senescence. Notably, we identify α-terpineol as an activator that effectively enhances TRF1 and TRF2 levels in a telomerase-independent manner, counteracting the senescence-associated decline in these crucial proteins. Moreover, α-terpineol ameliorates the cells’ response to oxidative DNA damage, particularly at the telomeric regions, thus preserving telomere length and delaying senescence. More importantly, our findings reveal the significance of the PI3K/AKT pathway in the regulation of shelterin components responsible for preserving telomere integrity. In conclusion, this study deepens our understanding of the molecular pathways involved in senescence-associated telomere dysfunction and highlights the potential of shelterin components to serve as targets of therapeutic interventions, aimed at promoting healthy aging and combating age-related diseases. Full article

(This article belongs to the Special Issue Antioxidants as Anti-Aging Interventions)

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19 pages, 3857 KiB

Open AccessArticle

Biological Response of Treatment with Saffron Petal Extract on Cytokine-Induced Oxidative Stress and Inflammation in the Caco-2/Human Leukemia Monocytic Co-Culture Model

by Federica De Cecco, Sara Franceschelli, Valeria Panella, Maria Anna Maggi, Silvia Bisti, Arturo Bravo Nuevo, Damiano D’Ardes, Francesco Cipollone and Lorenza Speranza

Antioxidants 2024, 13(10), 1257; https://doi.org/10.3390/antiox13101257 - 17 Oct 2024

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Abstract

The pathogenesis of Inflammatory Bowel Disease (IBD) involves complex mechanisms, including immune dysregulation, gut microbiota imbalances, oxidative stress, and defects in the gastrointestinal mucosal barrier. Current treatments for IBD often have significant limitations and adverse side effects, prompting a search for alternative therapeutic [...] Read more.

The pathogenesis of Inflammatory Bowel Disease (IBD) involves complex mechanisms, including immune dysregulation, gut microbiota imbalances, oxidative stress, and defects in the gastrointestinal mucosal barrier. Current treatments for IBD often have significant limitations and adverse side effects, prompting a search for alternative therapeutic strategies. Natural products with anti-inflammatory and antioxidant properties have demonstrated potential for IBD management. There is increasing interest in exploring food industry waste as a source of bioactive molecules with healthcare applications. In this study, a co-culture system of Caco-2 cells and PMA-differentiated THP-1 macrophages was used to simulate the human intestinal microenvironment. Inflammation was induced using TNF-α and IFN-γ, followed by treatment with Saffron Petal Extract (SPE). The results demonstrated that SPE significantly attenuated oxidative stress and inflammation by downregulating the expression of pro-inflammatory mediators such as iNOS, COX-2, IL-1β, and IL-6 via modulation of the NF-κB pathway. Given that NF-κB is a key regulator of macrophage-driven inflammation, our findings support further investigation of SPE as a potential complementary therapeutic agent for IBD treatment. Full article

(This article belongs to the Special Issue Antioxidants as Adjuvants for Inflammatory Bowel Disease Treatment)

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36 pages, 9902 KiB

Open AccessReview

Particulate Matter-Induced Emerging Health Effects Associated with Oxidative Stress and Inflammation

by Eun Yeong Lim and Gun-Dong Kim

Antioxidants 2024, 13(10), 1256; https://doi.org/10.3390/antiox13101256 - 17 Oct 2024

Viewed by 279

Abstract

Environmental pollution continues to increase with industrial development and has become a threat to human health. Atmospheric particulate matter (PM) was designated as a Group 1 carcinogen by the International Agency for Research on Cancer in 2013 and is an emerging global environmental [...] Read more.

Environmental pollution continues to increase with industrial development and has become a threat to human health. Atmospheric particulate matter (PM) was designated as a Group 1 carcinogen by the International Agency for Research on Cancer in 2013 and is an emerging global environmental risk factor that is a major cause of death related to cardiovascular and respiratory diseases. PM is a complex composed of highly reactive organic matter, chemicals, and metal components, which mainly cause excessive production of reactive oxygen species (ROS) that can lead to DNA and cell damage, endoplasmic reticulum stress, inflammatory responses, atherosclerosis, and airway remodeling, contributing to an increased susceptibility to and the exacerbation of various diseases and infections. PM has various effects on human health depending on the particle size, physical and chemical characteristics, source, and exposure period. PM smaller than 5 μm can penetrate and accumulate in the alveoli and circulatory system, causing harmful effects on the respiratory system, cardiovascular system, skin, and brain. In this review, we describe the relationship and mechanism of ROS-mediated cell damage, oxidative stress, and inflammatory responses caused by PM and the health effects on major organs, as well as comprehensively discuss the harmfulness of PM. Full article

(This article belongs to the Special Issue Environmental Pollution and Oxidative Stress)

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26 pages, 3745 KiB

Open AccessArticle

Exploring the 3,5-Dibromo-4,6-dimethoxychalcones and Their Flavone Derivatives as Dual α-Glucosidase and α-Amylase Inhibitors with Antioxidant and Anticancer Potential

by Jackson K. Nkoana, Malose J. Mphahlele, Garland K. More and Yee Siew Choong

Antioxidants 2024, 13(10), 1255; https://doi.org/10.3390/antiox13101255 - 17 Oct 2024

Viewed by 367

Abstract

The rising levels of type 2 diabetes mellitus (T2DM) and the poor medical effects of the commercially available antidiabetic drugs necessitate the development of potent analogs to treat this multifactorial metabolic disorder. It has been demonstrated that targeting two or more biochemical targets [...] Read more.

The rising levels of type 2 diabetes mellitus (T2DM) and the poor medical effects of the commercially available antidiabetic drugs necessitate the development of potent analogs to treat this multifactorial metabolic disorder. It has been demonstrated that targeting two or more biochemical targets associated with the onset and progression of diabetes along with oxidative stress and/or cancer could be a significant strategy for treating complications related to this metabolic disorder. The 3,5-dibromo-4,6-dimethoxychalcones (2a–f) and the corresponding flavone derivatives (3a–f) were synthesized and characterized using spectroscopic (NMR, HR-MS and FT-IR) techniques. The inhibitory effect of both series of compounds against α-glucosidase and α-amylase was evaluated in vitro through enzymatic assays. Selected compounds were also evaluated for potential to activate or inhibit superoxide dismutase. Compound 3c was selected as a representative model for the flavone series and evaluated spectrophotometrically for potential to coordinate Cu(II) and/or Zn(II) ions implicated in the metal-catalyzed free radical generation. A plausible mechanism for metal-chelation of the test compounds is presented. Furthermore, the most active compounds from each series against the test carbohydrate-hydrolyzing enzymes were selected and evaluated for their antigrowth effect on the human breast (MCF-7) and lung (A549) cancer cell lines and for cytotoxicity against the African Green Monkey kidney (Vero) cell line. The parent chalcone 2a and flavone derivatives 3a, 3c and 3e exhibited relatively high inhibitory activity against the MCF-7 cells with IC₅₀ values of 4.12 ± 0.55, 8.50 ± 0.82, 5.10 ± 0.61 and 6.96 ± 0.66 μM, respectively. The chalcones 2a and 2c exhibited significant cytotoxicity against the A549 cells with IC₅₀ values of 7.40 ± 0.67 and 9.68 ± 0.80 μM, respectively. Only flavone 3c exhibited relatively strong and comparable cytotoxicity against the MCF-7 and A549 cell lines with IC₅₀ values of 6.96 ± 0.66 and 6.42 ± 0.79 μM, respectively. Both series of compounds exhibited strong activity against the MCF-7 and A549 cell lines compared to the analogous quercetin (IC₅₀ = 35.40 ± 1.78 and 35.38 ± 1.78 μM, respectively) though moderate compared to nintedanib (IC₅₀ = 0.53 ± 0.11 and 0.74 ± 0.15 μM, respectively). The test compounds generally exhibited reduced cytotoxicity against the Vero cells compared to this anticancer drug. Molecular docking revealed strong alignment of the test compounds with the enzyme backbone to engage in hydrogen bonding interaction/s and hydrophobic contacts with the residues in the active sites of α-glucosidase and α-amylase. The test compounds possess favorable drug-likeness properties, supporting their potential as therapeutic candidates against T2DM. Full article

(This article belongs to the Special Issue From Natural to Synthetic Small-Molecule Antioxidants: New Candidates in Drug Discovery—Second Edition)

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18 pages, 13349 KiB

Open AccessReview

Innovations in Nuclear Medicine Imaging for Reactive Oxygen Species: Applications and Radiopharmaceuticals

by Joo Yeon Park, Sun Mi Park, Tae Sup Lee, Sang Ju Lee, Ji-Young Kim, Seung Jun Oh, Hai-Jeon Yoon, Bom Sahn Kim and Byung Seok Moon

Antioxidants 2024, 13(10), 1254; https://doi.org/10.3390/antiox13101254 - 17 Oct 2024

Viewed by 217

Abstract

Reactive oxygen species (ROS) are generated during normal cellular energy production and play a critical role in maintaining cellular function. However, excessive ROS can damage cells and tissues, contributing to the development of diseases such as cardiovascular, inflammatory, and neurodegenerative disorders. This review [...] Read more.

Reactive oxygen species (ROS) are generated during normal cellular energy production and play a critical role in maintaining cellular function. However, excessive ROS can damage cells and tissues, contributing to the development of diseases such as cardiovascular, inflammatory, and neurodegenerative disorders. This review explores the potential of nuclear medicine imaging techniques for detecting ROS and evaluates various radiopharmaceuticals used in these applications. Radiopharmaceuticals, which are drugs labeled with radionuclides, can bind to specific biomarkers, facilitating their identification in vivo using nuclear medicine equipment, i.e., positron emission tomography and single photon emission computed tomography, for diagnostic purposes. This review includes a comprehensive search of PubMed, covering radiopharmaceuticals such as analogs of fluorescent probes and antioxidant vitamin C, and biomarkers targeting mitochondrial complex I or cystine/glutamate transporter. Full article

(This article belongs to the Special Issue Development and Validation of Methods for Analysis of Oxidative Stress in Humans and Animals—2nd Edition)

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41 pages, 38449 KiB

Open AccessArticle

Metabolome and Metagenome Integration Unveiled Synthesis Pathways of Novel Antioxidant Peptides in Fermented Lignocellulosic Biomass of Palm Kernel Meal

by Hammad Qamar, Rong He, Yuanfei Li, Min Song, Dun Deng, Yiyan Cui, Miao Yu and Xianyong Ma

Antioxidants 2024, 13(10), 1253; https://doi.org/10.3390/antiox13101253 - 17 Oct 2024

Viewed by 206

Abstract

Approximately one-third of the entire world’s food resources are deemed to be wasted. Palm kernel meal (PKM), a product that is extensively generated by the palm oil industry, exhibits a unique nutrient-rich composition. However, its recycling is seldom prioritized due to numerous factors. [...] Read more.

Approximately one-third of the entire world’s food resources are deemed to be wasted. Palm kernel meal (PKM), a product that is extensively generated by the palm oil industry, exhibits a unique nutrient-rich composition. However, its recycling is seldom prioritized due to numerous factors. To evaluate the impact of enzymatic pretreatment and Lactobacillus plantarum and Lactobacillus reuteri fermentation upon the antioxidant activity of PKM, we implemented integrated metagenomics and metabolomics approaches. The substantially enhanced (p < 0.05) property of free radicals scavenging, as well as total flavonoids and polyphenols, demonstrated that the biotreated PKM exhibited superior antioxidant capacity. Non-targeted metabolomics disclosed that the Lactobacillus fermentation resulted in substantial (p < 0.05) biosynthesis of 25 unique antioxidant biopeptides, along with the increased (p < 0.05) enrichment ratio of the isoflavonoids and secondary metabolites biosynthesis pathways. The 16sRNA sequencing and correlation analysis revealed that Limosilactobacillus reuteri, Pediococcus acidilactici, Lacticaseibacillus paracasei, Pediococcus pentosaceus, Lactiplantibacillus plantarum, Limosilactobacillus fermentum, and polysaccharide lyases had significantly dominated (p < 0.05) proportions in PMEL, and these bacterial species were strongly (p < 0.05) positively interrelated with antioxidants peptides. Fermented PKM improves nutritional value by enhancing beneficial probiotics, enzymes, and antioxidants and minimizing anti-nutritional factors, rendering it an invaluable feed ingredient and gut health promoter for animals, multifunctional food elements, or as an ingredient in sustainable plant-based diets for human utilization, and functioning as a culture substrate in the food sector. Full article

(This article belongs to the Special Issue Methodologies for Improving Antioxidant Properties and Absorption)

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20 pages, 6780 KiB

Open AccessArticle

AIBP Protects Müller Glial Cells Against Oxidative Stress-Induced Mitochondrial Dysfunction and Reduces Retinal Neuroinflammation

by Seunghwan Choi, Soo-Ho Choi, Tonking Bastola, Keun-Young Kim, Sungsik Park, Robert N. Weinreb, Yury I. Miller and Won-Kyu Ju

Antioxidants 2024, 13(10), 1252; https://doi.org/10.3390/antiox13101252 - 17 Oct 2024

Viewed by 281

Abstract

Glaucoma, an optic neuropathy with the loss of retinal ganglion cells (RGCs), is a leading cause of irreversible vision loss. Oxidative stress and mitochondrial dysfunction have a significant role in triggering glia-driven neuroinflammation and subsequent glaucomatous RGC degeneration in the context of glaucoma. [...] Read more.

Glaucoma, an optic neuropathy with the loss of retinal ganglion cells (RGCs), is a leading cause of irreversible vision loss. Oxidative stress and mitochondrial dysfunction have a significant role in triggering glia-driven neuroinflammation and subsequent glaucomatous RGC degeneration in the context of glaucoma. It has previously been shown that apolipoprotein A-I binding protein (APOA1BP or AIBP) has an anti-inflammatory function. Moreover, Apoa1bp^−/− mice are characterized by retinal neuroinflammation and RGC loss. In this study, we found that AIBP deficiency exacerbated the oxidative stress-induced disruption of mitochondrial dynamics and function in the retina, leading to a further decline in visual function. Mechanistically, AIBP deficiency-induced oxidative stress triggered a reduction in glycogen synthase kinase 3β and dynamin-related protein 1 phosphorylation, optic atrophy type 1 and mitofusin 1 and 2 expression, and oxidative phosphorylation, as well as the activation of mitogen-activated protein kinase (MAPK) in Müller glia dysfunction, leading to cell death and inflammatory responses. In vivo, the administration of recombinant AIBP (rAIBP) effectively protected the structural and functional integrity of retinal mitochondria under oxidative stress conditions and prevented vision loss. In vitro, incubation with rAIBP safeguarded the structural integrity and bioenergetic performance of mitochondria and concurrently suppressed MAPK activation, apoptotic cell death, and inflammatory response in Müller glia. These findings support the possibility that AIBP promotes RGC survival and restores visual function in glaucomatous mice by ameliorating glia-driven mitochondrial dysfunction and neuroinflammation. Full article

(This article belongs to the Special Issue Cellular Responses of Antioxidants Related to Degenerative Eye Disease Research)

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18 pages, 2269 KiB

Open AccessArticle

Recovery of Selenium-Enriched Polysaccharides from Cardamine violifolia Residues: Comparison on Structure and Antioxidant Activity by Different Extraction Methods

by Yong Liang, Jiali Yu, Lulu Wu, Xin Cong, Haiyuan Liu, Xu Chen, Shuyi Li and Zhenzhou Zhu

Antioxidants 2024, 13(10), 1251; https://doi.org/10.3390/antiox13101251 - 17 Oct 2024

Viewed by 259

Abstract

The residues from selenium-enriched Cardamine violifolia after the extraction of protein were still rich in polysaccharides. Thus, the recovery of selenium polysaccharides (SePSs) was compared using hot water extraction and ultrasonic-assisted extraction techniques. The yield, extraction rate, purity, specific energy consumption, and content [...] Read more.

The residues from selenium-enriched Cardamine violifolia after the extraction of protein were still rich in polysaccharides. Thus, the recovery of selenium polysaccharides (SePSs) was compared using hot water extraction and ultrasonic-assisted extraction techniques. The yield, extraction rate, purity, specific energy consumption, and content of total and organic selenium from different SePS extracts were determined. The results indicated that at conditions of 250 W (ultrasonic power), 30 °C, and a liquid-to-material ratio of 30:1 extracted for 60 min, the yield of SePSs was 3.97

\pm

0.07%, the extraction rate was 22.76

\pm

0.40%, and the purity was 65.56

\pm

0.35%, while the total and organic selenium content was 749.16

\pm

6.91 mg/kg and 628.37

\pm

5.93 mg/kg, respectively. Compared to traditional hot water extraction, ultrasonic-assisted extraction significantly improves efficiency, reduces energy use, and boosts both total and organic selenium content in the extract. Measurements of particle size, molecular weight, and monosaccharide composition, along with infrared and ultraviolet spectroscopy, revealed that ultrasonic-assisted extraction breaks down long-chain structures, decreases particle size, and changes monosaccharide composition in SePSs, leading to lower molecular weight and reduced dispersity. The unique structure of SePSs, which integrates selenium with polysaccharide groups, results in markedly improved antioxidant activity and reducing power, even at low concentrations, due to the synergistic effects of selenium and polysaccharides. This study establishes a basis for using SePSs in functional foods. Full article

(This article belongs to the Special Issue Antioxidant and Protective Effects of Plant Extracts—2nd Edition)

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23 pages, 17221 KiB

Open AccessArticle

Aged Gut Microbiome Induces Metabolic Impairment and Hallmarks of Vascular and Intestinal Aging in Young Mice

by Chak-Kwong Cheng, Lianwei Ye, Yuanyuan Zuo, Yaling Wang, Li Wang, Fuyong Li, Sheng Chen and Yu Huang

Antioxidants 2024, 13(10), 1250; https://doi.org/10.3390/antiox13101250 - 17 Oct 2024

Viewed by 232

Abstract

Aging, an independent risk factor for cardiometabolic diseases, refers to a progressive deterioration in physiological function, characterized by 12 established hallmarks. Vascular aging is driven by endothelial dysfunction, telomere dysfunction, oxidative stress, and vascular inflammation. This study investigated whether aged gut microbiome promotes [...] Read more.

Aging, an independent risk factor for cardiometabolic diseases, refers to a progressive deterioration in physiological function, characterized by 12 established hallmarks. Vascular aging is driven by endothelial dysfunction, telomere dysfunction, oxidative stress, and vascular inflammation. This study investigated whether aged gut microbiome promotes vascular aging and metabolic impairment. Fecal microbiome transfer (FMT) was conducted from aged (>75 weeks old) to young C57BL/6 mice (8 weeks old) for 6 weeks. Wire myography was used to evaluate endothelial function in aortas and mesenteric arteries. ROS levels were measured by dihydroethidium (DHE) staining and lucigenin-enhanced chemiluminescence. Vascular and intestinal telomere function, in terms of relative telomere length, telomerase reverse transcriptase expression and telomerase activity, were measured. Systemic inflammation, endotoxemia and intestinal integrity of mice were assessed. Gut microbiome profiles were studied by 16S rRNA sequencing. Some middle-aged mice (40–42 weeks old) were subjected to chronic metformin treatment and exercise training for 4 weeks to evaluate their anti-aging benefits. Six-week FMT impaired glucose homeostasis and caused vascular dysfunction in aortas and mesenteric arteries in young mice. FMT triggered vascular inflammation and oxidative stress, along with declined telomerase activity and shorter telomere length in aortas. Additionally, FMT impaired intestinal integrity, and triggered AMPK inactivation and telomere dysfunction in intestines, potentially attributed to the altered gut microbial profiles. Metformin treatment and moderate exercise improved integrity, AMPK activation and telomere function in mouse intestines. Our data highlight aged microbiome as a mechanism that accelerates intestinal and vascular aging, suggesting the gut-vascular connection as a potential intervention target against cardiovascular aging and complications. Full article

(This article belongs to the Special Issue Free Radicals, Antioxidants, and Oxidative Stress in Aging and Age-Related Diseases—2nd Edition)

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22 pages, 2358 KiB

Open AccessReview

Oxidative Stress in Cataract Formation: Is There a Treatment Approach on the Horizon?

by Jingyan Li, Francesco Buonfiglio, Ying Zeng, Norbert Pfeiffer and Adrian Gericke

Antioxidants 2024, 13(10), 1249; https://doi.org/10.3390/antiox13101249 - 16 Oct 2024

Viewed by 485

Abstract

Cataracts, a leading cause of blindness worldwide, are closely linked to oxidative stress-induced damage to lens epithelial cells (LECs). Key factors contributing to cataract formation include aging, arterial hypertension, and diabetes mellitus. Given the high global prevalence of cataracts, the burden of cataract-related [...] Read more.

Cataracts, a leading cause of blindness worldwide, are closely linked to oxidative stress-induced damage to lens epithelial cells (LECs). Key factors contributing to cataract formation include aging, arterial hypertension, and diabetes mellitus. Given the high global prevalence of cataracts, the burden of cataract-related visual impairment is substantial, highlighting the need for pharmacological strategies to supplement surgical interventions. Understanding the molecular pathways involved in oxidative stress during cataract development may offer valuable insights for designing novel therapeutic approaches. This review explores the role of oxidative stress in cataract formation, focusing on critical mechanisms, such as mitochondrial dysfunction, endoplasmic reticulum stress, loss of gap junctions, and various cell death pathways in LECs. Additionally, we discuss emerging therapeutic strategies and potential targeting options, including antioxidant-based treatments. Full article

(This article belongs to the Special Issue Oxidative Stress in Cataracts: Mechanisms and Therapies)

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28 pages, 10692 KiB

Open AccessArticle

Design, Synthesis, and Anti-Melanogenic Activity of 2-Mercaptomethylbenzo[d]imidazole Derivatives Serving as Tyrosinase Inhibitors: An In Silico, In Vitro, and In Vivo Exploration

by Hee Jin Jung, Hyeon Seo Park, Hye Jin Kim, Hye Soo Park, Yujin Park, Pusoon Chun, Hae Young Chung and Hyung Ryong Moon

Antioxidants 2024, 13(10), 1248; https://doi.org/10.3390/antiox13101248 - 16 Oct 2024

Viewed by 267

Abstract

2-Mercaptomethylbenzo[d]imidazole (2-MMBI) derivatives were designed and synthesized as tyrosinase (TYR) chelators using 2-mercaptomethylimidazole scaffolds. Seven of the ten 2-MMBI derivatives exhibited stronger inhibition of mushroom TYR activity than kojic acid. Their ability to chelate copper ions was demonstrated through experiments using [...] Read more.

2-Mercaptomethylbenzo[d]imidazole (2-MMBI) derivatives were designed and synthesized as tyrosinase (TYR) chelators using 2-mercaptomethylimidazole scaffolds. Seven of the ten 2-MMBI derivatives exhibited stronger inhibition of mushroom TYR activity than kojic acid. Their ability to chelate copper ions was demonstrated through experiments using the copper chelator pyrocatechol violet and assays measuring TYR activity in the presence or absence of exogenous CuSO₄. The inhibition mechanisms of derivatives 1, 3, 8, and 9, which showed excellent TYR inhibitory activity, were elucidated through kinetic studies and supported by the docking simulation results. Derivatives 3, 7, 8, and 10 significantly inhibited cellular TYR activity and melanin production in B16F10 cells in a dose-dependent manner, with stronger potency than kojic acid. Furthermore, in situ, derivatives 7 and 10 showed stronger inhibitory effects on B16F10 cell TYR activity than kojic acid. Six derivatives, including 8, showed highly potent depigmentation in zebrafish larvae, outpacing kojic acid even at 200–670 times lower concentrations. Additionally, all derivatives could scavenge for reactive oxygen species without causing cytotoxicity in epidermal cells. These results suggested that 2-MMBI derivatives are promising anti-melanogenic agents. Full article

(This article belongs to the Special Issue From Natural to Synthetic Small-Molecule Antioxidants: New Candidates in Drug Discovery—Second Edition)

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4 pages, 176 KiB

Open AccessEditorial

Achievements in Applications of Antioxidants and Bioactive Compounds in Food: From Agriculture to Health Benefits

by Mia Kurek, Frédéric Debeaufort and Andrée Voilley

Antioxidants 2024, 13(10), 1247; https://doi.org/10.3390/antiox13101247 - 16 Oct 2024

Viewed by 268

Abstract

Natural foods and food components are becoming increasingly popular worldwide because people are concerned about eating healthy diets [...] Full article

(This article belongs to the Special Issue Application of Antioxidants and Bioactive Compounds in Food from Agriculture to Health Benefits, 2nd Edition)

25 pages, 8574 KiB

Open AccessArticle

Baicalein Ameliorates Insulin Resistance of HFD/STZ Mice through Activating PI3K/AKT Signal Pathway of Liver and Skeletal Muscle in a GLP-1R-Dependent Manner

by Na Liu, Xin Cui, Tingli Guo, Xiaotong Wei, Yuzhuo Sun, Jieyun Liu, Yangyang Zhang, Weina Ma, Wenhui Yan and Lina Chen

Antioxidants 2024, 13(10), 1246; https://doi.org/10.3390/antiox13101246 - 16 Oct 2024

Viewed by 328

Abstract

Insulin resistance (IR) is the principal pathophysiological change occurring in diabetes mellitus (DM). Baicalein, a bioactive flavonoid primarily extracted from the medicinal plant Scutellaria baicalensis Georgi, has been shown in our previous research to be a potential natural glucagon-like peptide-1 receptor (GLP-1R) [...] Read more.

Insulin resistance (IR) is the principal pathophysiological change occurring in diabetes mellitus (DM). Baicalein, a bioactive flavonoid primarily extracted from the medicinal plant Scutellaria baicalensis Georgi, has been shown in our previous research to be a potential natural glucagon-like peptide-1 receptor (GLP-1R) agonist. However, the exact therapeutic effect of baicalein on DM and its underlying mechanisms remain elusive. In this study, we investigated the therapeutic effects of baicalein on diabetes and sought to clarify its underlying molecular mechanisms. Our results demonstrated that baicalein improves hyperglycemic, hyperinsulinemic, and glucometabolic disorders in mice with induced diabetes via GLP-1R. This was confirmed by the finding that baicalein’s effects on improving IR were largely diminished in mice with whole-body Glp1r ablation. Complementarily, network pharmacology analysis highlighted the pivotal involvement of the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) insulin signaling pathway in the therapeutic actions of baicalein on IR. Our mechanism research significantly confirmed that baicalein mitigates hepatic and muscular IR through the PI3K/AKT signal pathway, both in vitro and in vivo. Furthermore, we demonstrated that baicalein enhances glucose uptake in skeletal muscle cells under IR conditions through the Ca²⁺/calmodulin-dependent protein kinase II (CaMKII)-adenosine 5′-monophosphate-activated protein kinase (AMPK)-glucose transporter 4 (GLUT4) signaling pathway in a GLP-1R-dependent manner. In conclusion, our findings confirm the therapeutic effects of baicalein on IR and reveal that it improves IR in liver and muscle tissues through the PI3K/AKT insulin signaling pathway in a GLP-1R dependent manner. Moreover, we clarified that baicalein enhances the glucose uptake in skeletal muscle tissue through the Ca²⁺/CaMKII-AMPK-GLUT4 signal pathway. Full article

(This article belongs to the Special Issue Natural Products: Biological, Antioxidant Properties and Health Effects—3rd Edition)

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12 pages, 3758 KiB

Open AccessArticle

Physiological and Microstructure Analysis Reveals the Mechanism by Which Formic Acid Delays Postharvest Physiological Deterioration of Cassava

by Yannian Che, Zhongping Ding, Chen Shen, Alisdair R. Fernie, Xiangning Tang, Yuan Yao, Jiao Liu, Yajie Wang, Ruimei Li and Jianchun Guo

Antioxidants 2024, 13(10), 1245; https://doi.org/10.3390/antiox13101245 - 16 Oct 2024

Viewed by 246

Abstract

Formic acid is reported to act as a food preservative and feed additive, but its effects on controlling postharvest physiological deterioration (PPD) development in cassava are unclear. In this study, we assessed the effectiveness of different concentrations of formic acid in attenuating PPD [...] Read more.

Formic acid is reported to act as a food preservative and feed additive, but its effects on controlling postharvest physiological deterioration (PPD) development in cassava are unclear. In this study, we assessed the effectiveness of different concentrations of formic acid in attenuating PPD occurrence in fresh-cut cassava. The results showed that the concentration of 0.1% (v/v) formic acid could significantly delay the occurrence of PPD, and that the higher the concentration of formic acid supplied, the later the occurrence of PPD symptoms. The physiological and biochemical analysis of 0.5%-formic-acid-treated cassava slices revealed that formic acid decreased the degradation of starch, inhibited the accumulation of hydrogen peroxide (H₂O₂), malondialdehyde (MDA), and water-soluble pectin in cassava slices with PPD development, and increased the activities of the antioxidant enzymes ascorbate peroxidase (APX) and glutathione reductase (GR). A microscopic observation showed that the formic acid treatment inhibited the enlargement of the intercellular space during the cassava PPD process, which suggests that the formation of an intercellular layer of the cell wall was inhibited by formic acid. This study thus revealed the mechanism used by formic acid to extend the cassava shelf life; however, a detailed evaluation of the possible side effects on, for example, the cyanide content will be needed to categorically ensure the safety of this method. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidant Defense in Crop Plants)

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18 pages, 1505 KiB

Open AccessArticle

Comparative Bioaccesibility Study of Cereal-Based Nutraceutical Ingredients Using INFOGEST Static, Semi-Dynamic and Dynamic In Vitro Gastrointestinal Digestion

by Iván Jesús Jiménez-Pulido, Ana Belén Martín-Diana, Daniel de Luis and Daniel Rico

Antioxidants 2024, 13(10), 1244; https://doi.org/10.3390/antiox13101244 - 16 Oct 2024

Viewed by 290

Abstract

Efficient development of effective functional foods and nutraceuticals requires adequate estimation methods of the bioaccessibility of their bioactive compounds. Specially grain-based nutraceuticals and functional ingredients are often enriched in bound/low bioavailable bioactive phytochemicals. The objective of this work was to evaluate the differences [...] Read more.

Efficient development of effective functional foods and nutraceuticals requires adequate estimation methods of the bioaccessibility of their bioactive compounds. Specially grain-based nutraceuticals and functional ingredients are often enriched in bound/low bioavailable bioactive phytochemicals. The objective of this work was to evaluate the differences in applying static or dynamic digestion models for the estimation of bioaccessibility of antioxidants present in cereal grain-based/fiber-rich ingredients produced using enzymatic hydrolysis and sprouting processes. Main liberated phenolic compounds, antioxidant activity (ABTS^•+ and ORAC) and ferric reducing capacity were evaluated in the samples following three digestion protocols with differences based on their dynamism: static, semi-dynamic and dynamic. The samples digested with the dynamic method showed higher antioxidant and reducing capacities than those digested with the static and semi-dynamic protocols. The results obtained from the digests with the dynamic model showed a total phenol content (TPs) ranging from 1068.22 to 1456.65 μmol GAE 100 g⁻¹ and antioxidant capacity values from 7944.62 to 15,641.90 μmol TE 100 g⁻¹ (ORAC) and from 8454.08 to 11,002.64 μmol TE 100 g⁻¹ (ABTS^•+), with a reducing power ranging from 2103.32 to 2679.78 mmol Fe reduced 100 g⁻¹ (FRAP). The dynamic character of the protocols used for developing bioactive cereal-based foods significantly affects the estimation of their bioaccessibility, probably giving a better approach to their potential bioavailability in in vivo systems. Full article

(This article belongs to the Special Issue Valorization of the Antioxidant Power of Natural Compounds)

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3 pages, 163 KiB

Open AccessEditorial

On the Therapeutic Potential of Heme Oxygenase-1 and Its Metabolites

by David E. Stec

Antioxidants 2024, 13(10), 1243; https://doi.org/10.3390/antiox13101243 - 16 Oct 2024

Viewed by 297

Abstract

Over the past 55 years, the heme oxygenase (HO) system has emerged as a pivotal player in a myriad of cellular, tissue, and integrative physiological processes [...] Full article

(This article belongs to the Special Issue Pharmacological and Clinical Significance of Heme Oxygenase-1 2022)

42 pages, 1858 KiB

Open AccessReview

Vitamin C in the Management of Thyroid Cancer: A Highway to New Treatment?

by Francesca Gorini and Alessandro Tonacci

Antioxidants 2024, 13(10), 1242; https://doi.org/10.3390/antiox13101242 - 15 Oct 2024

Viewed by 466

Abstract

Thyroid cancer (TC) is the most common endocrine malignancy, with an increased global incidence in recent decades, despite a substantially unchanged survival. While TC has an excellent overall prognosis, some types of TC are associated with worse patient outcomes, depending on the genetic [...] Read more.

Thyroid cancer (TC) is the most common endocrine malignancy, with an increased global incidence in recent decades, despite a substantially unchanged survival. While TC has an excellent overall prognosis, some types of TC are associated with worse patient outcomes, depending on the genetic setting. Furthermore, oxidative stress is related to more aggressive features of TC. Vitamin C, an essential nutrient provided with food or as a dietary supplement, is a well-known antioxidant and a scavenger of reactive oxygen species; however, at high doses, it can induce pro-oxidant effects, acting through multiple biological mechanisms that play a crucial role in killing cancer cells. Although experimental data and, less consistently, clinical studies, suggest the possibility of antineoplastic effects of vitamin C at pharmacological doses, the antitumor efficacy of this nutrient in TC remains at least partly unexplored. Therefore, this review discusses the current state of knowledge on the role of vitamin C, alone or in combination with other conventional therapies, in the management of TC, the mechanisms underlying this association, and the perspectives that may emerge in TC treatment strategies, and, also, in light of the development of novel functional foods useful to this extent, by implementing novel sensory analysis strategies. Full article

(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Carcinogenesis: A Multifaceted Approach)

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