Antioxidants

22 pages, 2710 KiB

Open AccessArticle

Arctigenin from Fructus arctii Exhibits Antiaging Effects via Autophagy Induction, Antioxidative Stress, and Increase in Telomerase Activity in Yeast

by Siqi Chen, Yajing Li, Enchan Wu, Qing Li, Lan Xiang and Jianhua Qi

Antioxidants 2024, 13(6), 684; https://doi.org/10.3390/antiox13060684 (registering DOI) - 2 Jun 2024

Abstract

Aging is often accompanied by irreversible decline in body function, which causes a large number of age-related diseases and brings a huge economic burden to society and families. Many traditional Chinese medicines have been known to extend lifespan, but it has still been [...] Read more.

Aging is often accompanied by irreversible decline in body function, which causes a large number of age-related diseases and brings a huge economic burden to society and families. Many traditional Chinese medicines have been known to extend lifespan, but it has still been a challenge to isolate a single active molecule from them and verify the mechanism of anti-aging action. Drugs that inhibit senescence-associated secretory phenotypes (SASPs) are called “senomorphics”. In this study, arctigenin (ATG), a senomorphic, was screened from the Chinese medicine Fructus arctii using K6001 yeast replicative lifespan. Autophagy, oxidative stress, and telomerase activity are key mechanisms related to aging. We found that ATG may act through multiple mechanisms to become an effective anti-aging molecule. In exploring the effect of ATG on autophagy, it was clearly observed that ATG significantly enhanced autophagy in yeast. We further verified that ATG can enhance autophagy by targeting protein phosphatase 2A (PP2A), leading to an increased lifespan. Meanwhile, we evaluated the antioxidant capacity of ATG and found that ATG increased the activities of the antioxidant enzymes, thereby reducing reactive oxygen species (ROS) and malondialdehyde (MDA) levels to improve the survival of yeast under oxidative stress. In addition, ATG was able to increase telomerase activity by enhancing the expression of EST1, EST2, and EST3 genes in yeast. In conclusion, ATG exerts anti-aging effects through induction of autophagy, antioxidative stress, and enhancement of telomerase activity in yeast, which is recognized as a potential molecule with promising anti-aging effects, deserving in-depth research in the future. Full article

(This article belongs to the Collection Advances in Antioxidant Ingredients from Natural Products)

19 pages, 838 KiB

Open AccessArticle

Formulation and Physical–Chemical Analysis of Functional Muffin Made with Inulin, Moringa, and Cacao Adapted for Elderly People with Parkinson’s Disease

by Paula García-Milla, Rocío Peñalver and Gema Nieto

Antioxidants 2024, 13(6), 683; https://doi.org/10.3390/antiox13060683 (registering DOI) - 31 May 2024

Abstract

Parkinson’s disease (PD) is a neurodegenerative disorder that affects people’s health. Constipation is probably one of the most prominent gastrointestinal symptoms (non-motor symptoms) of PD with devastating consequences. The aim of this research work is to formulate a functional food product, supplemented with [...] Read more.

Parkinson’s disease (PD) is a neurodegenerative disorder that affects people’s health. Constipation is probably one of the most prominent gastrointestinal symptoms (non-motor symptoms) of PD with devastating consequences. The aim of this research work is to formulate a functional food product, supplemented with inulin, cocoa, and Moringa, which can be an adjuvant in the treatment of constipation. The product was prepared according to a muffin or “Chilean cake” recipe; this basic muffin was prepared with additions of inulin (MI), inulin + cacao (MIC), and inulin + Moringa (MIM). A physical–chemical analysis of the macronutrients and an antioxidant capacity assessment of the samples were conducted, as well as a sensory evaluation performed by a group of people suffering from Parkinson’s disease. A statistically significant difference was observed in the soluble (p = 0.0023) and insoluble (p = 0.0015) fiber values between the control samples and all samples. Furthermore, inulin + cacao improved the antioxidant capacity and folate intake compared to the control. Inulin alone has been shown to have antioxidant capacity according to ABTS (262.5728 ± 34.74 μmol TE/g) and DPPH (9.092518 ± 10.43 μmol TE/g) assays. A sensory evaluation showed a preference for the product with inulin and for the product with inulin + cacao, with a 78% purchase intention being reported by the subjects who evaluated the products. The incorporation of inulin and cacao improved the nutritional value of the muffins; the dietary fiber, antioxidant capacity and folate content are some of the features that stood out. A bakery product enriched with inulin, cocoa and Moringa could serve as a nutritional strategy to enhance nutritional value, thus helping in the treatment of constipation. Full article

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

18 pages, 4987 KiB

Open AccessArticle

Palm Kernel Cake Extracts Obtained from the Combination of Bacterial Fermentation and Enzymic Hydrolysis Promote Swine Small Intestine IPEC-J2 Cell Proliferation and Alleviate LPS-Induced Inflammation In Vitro

by Hui Zeng, Jingna Miao, Jinghong Liao, Zhiyuan Sui, Meixin Hou and Suqin Hang

Antioxidants 2024, 13(6), 682; https://doi.org/10.3390/antiox13060682 (registering DOI) - 31 May 2024

Abstract

Co-fermentation with bacteria and enzymes can reduce sugar content in palm kernel cake (PKC); however, the chemical changes and their effects on cell functionality are unclear. This study investigated the active components in pre-treated PKC extracts and their effects on pig small intestine [...] Read more.

Co-fermentation with bacteria and enzymes can reduce sugar content in palm kernel cake (PKC); however, the chemical changes and their effects on cell functionality are unclear. This study investigated the active components in pre-treated PKC extracts and their effects on pig small intestine IPEC-J2 cell proliferation and LPS-induced inflammation. The extracts contained 60.75% sugar, 36.80% mannose, 1.75% polyphenols and 0.59% flavone, as determined by chemical analyses, suggesting that the extracts were palm kernel cake oligosaccharides (PKCOS). Then, we found that 1000 µg/mL PKCOS counteracted the decrease in cell viability (CCK8 kit) caused by LPS induction by 5 µg/mL LPS (p < 0.05). Mechanistic studies conducted by RNA-seq and qPCR analyses suggested PKCOS promoted cell proliferation through the upregulation of TNF-α, PI3KAP1, MAP3K5 and Fos in the PI3K/MAPK signalling pathway; alleviated inflammation caused by LPS via the downregulation of the target genes Casp3 and TNF-α in association with apoptosis; and regulated the expression of the antioxidant genes SOD1, SOD2 and GPX4 to exert positive antioxidant effects (p < 0.05). Furthermore, PKCOS upregulated SLC5A1 (encoding SLGT1), HK and MPI in the glycolytic pathway (p < 0.05), suggesting cell survival. In summary, PKCOS has positive effects on promoting swine intestine cell proliferation against inflammation. Full article

33 pages, 1158 KiB

Open AccessReview

Protein Oxidative Modifications in Neurodegenerative Diseases: From Advances in Detection and Modelling to Their Use as Disease Biomarkers

by Sandra I. Anjo, Zhicheng He, Zohaib Hussain, Aruba Farooq, Alan McIntyre, Charles A. Laughton, Andreia Neves Carvalho and Mattéa J. Finelli

Antioxidants 2024, 13(6), 681; https://doi.org/10.3390/antiox13060681 (registering DOI) - 31 May 2024

Abstract

Oxidation–reduction post-translational modifications (redox-PTMs) are chemical alterations to amino acids of proteins. Redox-PTMs participate in the regulation of protein conformation, localization and function, acting as signalling effectors that impact many essential biochemical processes in the cells. Crucially, the dysregulation of redox-PTMs of proteins [...] Read more.

Oxidation–reduction post-translational modifications (redox-PTMs) are chemical alterations to amino acids of proteins. Redox-PTMs participate in the regulation of protein conformation, localization and function, acting as signalling effectors that impact many essential biochemical processes in the cells. Crucially, the dysregulation of redox-PTMs of proteins has been implicated in the pathophysiology of numerous human diseases, including neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. This review aims to highlight the current gaps in knowledge in the field of redox-PTMs biology and to explore new methodological advances in proteomics and computational modelling that will pave the way for a better understanding of the role and therapeutic potential of redox-PTMs of proteins in neurodegenerative diseases. Here, we summarize the main types of redox-PTMs of proteins while providing examples of their occurrence in neurodegenerative diseases and an overview of the state-of-the-art methods used for their detection. We explore the potential of novel computational modelling approaches as essential tools to obtain insights into the precise role of redox-PTMs in regulating protein structure and function. We also discuss the complex crosstalk between various PTMs that occur in living cells. Finally, we argue that redox-PTMs of proteins could be used in the future as diagnosis and prognosis biomarkers for neurodegenerative diseases. Full article

(This article belongs to the Special Issue Protein Oxidative Modification in Brain function, Brain Ageing and Neurological Diseases)

18 pages, 4369 KiB

Open AccessArticle

Co-Microencapsulation of Cushuro (Nostoc sphaericum) Polysaccharide with Sacha Inchi Oil (Plukenetia huayllabambana) and Natural Antioxidant Extracts

by Nancy Chasquibol, Axel Sotelo, Mateo Tapia, Rafael Alarcón, Francisco Goycoolea and María del Carmen Perez-Camino

Antioxidants 2024, 13(6), 680; https://doi.org/10.3390/antiox13060680 (registering DOI) - 31 May 2024

Abstract

Cushuro (Nostoc sphaericum) polysaccharide was used to co-microencapsulate sacha inchi oil, natural antioxidant extracts from the oleoresin of charapita chili peppers (Capsicum frutescens L.) and grape orujo (Vitis vinifera L.). Encapsulation efficiency, moisture, particle size, morphology, oxidative stability, shelf-life, [...] Read more.

Cushuro (Nostoc sphaericum) polysaccharide was used to co-microencapsulate sacha inchi oil, natural antioxidant extracts from the oleoresin of charapita chili peppers (Capsicum frutescens L.) and grape orujo (Vitis vinifera L.). Encapsulation efficiency, moisture, particle size, morphology, oxidative stability, shelf-life, solubility, essential fatty acid profile, sterol content and antioxidant capacity were evaluated. The formulations with grape orujo extract showed higher oxidative stability (4908 ± 184 h), antioxidant capacity (4835.33 ± 40.02 µg Trolox/g ms), higher phenolic contents (960.11 ± 53.59 µg AGE/g ms) and a smaller particle size (7.55 µm) than the other formulations, as well as good solubility and a low moisture content. Therefore, grape orujo extracts can be used as natural antioxidants. The fatty acid composition (ω-3) remained quite stable in all the formulations carried out, which also occurred for sterols and tocopherols. In combination with gum arabic, grape orujo extract offered oxidative protection to sacha inchi oil during the first week of storage. Full article

(This article belongs to the Section Extraction and Industrial Applications of Antioxidants)

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24 pages, 8312 KiB

Open AccessArticle

Lovastatin-Induced Mitochondrial Oxidative Stress Leads to the Release of mtDNA to Promote Apoptosis by Activating cGAS-STING Pathway in Human Colorectal Cancer Cells

by Xiaoming Huang, Ning Liang, Fuming Zhang, Wanjun Lin and Wenzhe Ma

Antioxidants 2024, 13(6), 679; https://doi.org/10.3390/antiox13060679 (registering DOI) - 31 May 2024

Abstract

Statins are 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors widely used in the treatment of hyperlipidemia. The inhibition of HMG-CoA reductase in the mevalonate pathway leads to the suppression of cell proliferation and induction of apoptosis. The cyclic GMP-AMP synthase (cGAS) stimulator of the interferon [...] Read more.

Statins are 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase inhibitors widely used in the treatment of hyperlipidemia. The inhibition of HMG-CoA reductase in the mevalonate pathway leads to the suppression of cell proliferation and induction of apoptosis. The cyclic GMP-AMP synthase (cGAS) stimulator of the interferon genes (STING) signaling pathway has been suggested to not only facilitate inflammatory responses and the production of type I interferons (IFN), but also activate other cellular processes, such as apoptosis. It has not been studied, however, whether cGAS-STING activation is involved in the apoptosis induced by statin treatment in human colorectal cancer cells. In this study, we reported that lovastatin impaired mitochondrial function, including the depolarization of mitochondrial membrane potential, reduction of oxygen consumption, mitochondrial DNA (mtDNA) integrity, and mtDNA abundance in human colorectal cancer HCT116 cells. The mitochondrial dysfunction markedly induced ROS production in mitochondria, whereas the defect in mitochondria respiration or depletion of mitochondria eliminated reactive oxygen species (ROS) production. The ROS-induced oxidative DNA damage by lovastatin treatment was attenuated by mitochondrial-targeted antioxidant mitoquinone (mitoQ). Upon DNA damage, mtDNA was released into the cytosol and bound to DNA sensor cGAS, thus activating the cGAS-STING signaling pathway to trigger a type I interferon response. This effect was not activated by nuclear DNA (nuDNA) or mitochondria RNA, as the depletion of mitochondria compromised this effect, but not the knockdown of retinoic acid-inducible gene-1/melanoma differentiation-associated protein 5 (RIG-I/MDA5) adaptor mitochondrial antiviral signaling protein (MAVS). Moreover, lovastatin-induced apoptosis was partly dependent on the cGAS-STING signaling pathway in HCT116 cells as the knockdown of cGAS or STING expression rescued cell viability and mitigated apoptosis. Similarly, the knockdown of cGAS or STING also attenuated the antitumor effect of lovastatin in the HCT116 xenograft model in vivo. Our findings suggest that lovastatin-induced apoptosis is at least partly mediated through the cGAS-STING signaling pathway by triggering mtDNA accumulation in the cytosol in human colorectal cancer HCT116 cells. Full article

(This article belongs to the Section ROS, RNS and RSS)

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20 pages, 1978 KiB

Open AccessReview

The Coming Age of Antisense Oligos for the Treatment of Hepatic Ischemia/Reperfusion (IRI) and Other Liver Disorders: Role of Oxidative Stress and Potential Antioxidant Effect

by Siyuan Yao, Aanchal Kasargod, Richard Chiu, Taylor R. Torgerson, Jerzy W. Kupiec-Weglinski and Kenneth J. Dery

Antioxidants 2024, 13(6), 678; https://doi.org/10.3390/antiox13060678 (registering DOI) - 31 May 2024

Abstract

Imbalances in the redox state of the liver arise during metabolic processes, inflammatory injuries, and proliferative liver disorders. Acute exposure to intracellular reactive oxygen species (ROS) results from high levels of oxidative stress (OxS) that occur in response to hepatic ischemia/reperfusion injury (IRI) [...] Read more.

Imbalances in the redox state of the liver arise during metabolic processes, inflammatory injuries, and proliferative liver disorders. Acute exposure to intracellular reactive oxygen species (ROS) results from high levels of oxidative stress (OxS) that occur in response to hepatic ischemia/reperfusion injury (IRI) and metabolic diseases of the liver. Antisense oligonucleotides (ASOs) are an emerging class of gene expression modulators that target RNA molecules by Watson–Crick binding specificity, leading to RNA degradation, splicing modulation, and/or translation interference. Here, we review ASO inhibitor/activator strategies to modulate transcription and translation that control the expression of enzymes, transcription factors, and intracellular sensors of DNA damage. Several small-interfering RNA (siRNA) drugs with N-acetyl galactosamine moieties for the liver have recently been approved. Preclinical studies using short-activating RNAs (saRNAs), phosphorodiamidate morpholino oligomers (PMOs), and locked nucleic acids (LNAs) are at the forefront of proof-in-concept therapeutics. Future research targeting intracellular OxS-related pathways in the liver may help realize the promise of precision medicine, revolutionizing the customary approach to caring for and treating individuals afflicted with liver-specific conditions. Full article

(This article belongs to the Special Issue New Strategies in Preventing Inflammatory and/or Oxidative-Stress-Induced Damages in Ischemia–Reperfusion Injury)

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15 pages, 2453 KiB

Open AccessArticle

TNFα Induces DNA and Histone Hypomethylation and Pulmonary Artery Smooth Muscle Cell Proliferation Partly via Excessive Superoxide Formation

by Patrick Crosswhite and Zhongjie Sun

Antioxidants 2024, 13(6), 677; https://doi.org/10.3390/antiox13060677 (registering DOI) - 31 May 2024

Abstract

Objective: The level of tumor necrosis factor-α (TNF-α) is upregulated during the development of pulmonary vascular remodeling and pulmonary hypertension. A hallmark of pulmonary arterial (PA) remodeling is the excessive proliferation of PA smooth muscle cells (PASMCs). The purpose of this study is [...] Read more.

Objective: The level of tumor necrosis factor-α (TNF-α) is upregulated during the development of pulmonary vascular remodeling and pulmonary hypertension. A hallmark of pulmonary arterial (PA) remodeling is the excessive proliferation of PA smooth muscle cells (PASMCs). The purpose of this study is to investigate whether TNF-α induces PASMC proliferation and explore the potential mechanisms. Methods: PASMCs were isolated from 8-week-old male Sprague-Dawley rats and treated with 0, 20, or 200 ng/mL TNF-α for 24 or 48 h. After treatment, cell number, superoxide production, histone acetylation, DNA methylation, and histone methylation were assessed. Results: TNF-α treatment increased NADPH oxidase activity, superoxide production, and cell numbers compared to untreated controls. TNF-α-induced PASMC proliferation was rescued by a superoxide dismutase mimetic tempol. TNF-α treatment did not affect histone acetylation at either dose but did significantly decrease DNA methylation. DNA methyltransferase 1 activity was unchanged by TNF-α treatment. Further investigation using QRT-RT-PCR revealed that GADD45-α, a potential mediator of DNA demethylation, was increased after TNF-α treatment. RNAi inhibition of GADD45-α alone increased DNA methylation. TNF-α impaired the epigenetic mechanism leading to DNA hypomethylation, which can be abolished by a superoxide scavenger tempol. TNF-α treatment also decreased H3-K4 methylation. TNF-α-induced PASMC proliferation may involve the H3-K4 demethylase enzyme, lysine-specific demethylase 1 (LSD1). Conclusions: TNF-α-induced PASMC proliferation may be partly associated with excessive superoxide formation and histone and DNA methylation. Full article

(This article belongs to the Special Issue Understanding Oxidative Stress in Cardiovascular Disorders)

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12 pages, 1097 KiB

Open AccessArticle

Occupational Exposure to Metal-Based Nanomaterials: A Possible Relationship between Chemical Composition and Oxidative Stress Biomarkers

by Valeria Bellisario, Giacomo Garzaro, Giulia Squillacioti, Marco Panizzolo, Federica Ghelli, Giuseppe Mariella, Roberto Bono, Irina Guseva Canu and Enrico Bergamaschi

Antioxidants 2024, 13(6), 676; https://doi.org/10.3390/antiox13060676 (registering DOI) - 31 May 2024

Abstract

Nanomaterials (NMs) are in high demand for a wide range of practical applications; however, comprehensively understanding the toxicity of these materials is a complex challenge, due to the limited availability of epidemiological evidence on the human health effects arising from workplace exposures. The [...] Read more.

Nanomaterials (NMs) are in high demand for a wide range of practical applications; however, comprehensively understanding the toxicity of these materials is a complex challenge, due to the limited availability of epidemiological evidence on the human health effects arising from workplace exposures. The aim of this work is to assess whether and how urinary metal concentrations could be reliable and useful in NM biomonitoring. In the framework of “NanoExplore Project” [EU LIFE17 Grant ENV/GR/000285], 43 not-exposed subjects and 40 exposed workers were recruited to measure exposure to NMs (PCN and LDSA) in the proximity of the workstations and biological biomarkers (urinary metal concentrations—Aluminum (Al), Silica (Si), Titanium (Ti), and Chromium (Cr); urinary OS biomarkers—TAP, Isop, and MDA). The results showed that Si and Ti were directly associated with NM exposure (both PCN and LDSA), as well as with OS biomarkers, especially in exposed workers. Moreover, the mediation analyses showed that Si could account for about 2.8% in the relationship between LDSA and OS biomarkers, possibly by decreasing OS antioxidant defenses in exposed people. In conclusion, our study provides evidence that occupational exposure to mixtures containing NMs can represent an underestimated hazard for exposed people, increasing the body burden and the oxidative balance. Full article

(This article belongs to the Special Issue Oxidative Stress Induced by Air Pollution)

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18 pages, 7004 KiB

Open AccessArticle

Senegenin Attenuates Pulmonary Fibrosis by Inhibiting Oxidative-Stress-Induced Epithelial Cell Senescence through Activation of the Sirt1/Pgc-1α Signaling Pathway

by Qian Zeng, Yuyang Luo, Xiaoxue Sang, Minlin Liao, Binbin Wen, Zhengang Hu, Mei Sun, Ziqiang Luo, Xiaoting Huang, Wei Liu and Siyuan Tang

Antioxidants 2024, 13(6), 675; https://doi.org/10.3390/antiox13060675 (registering DOI) - 31 May 2024

Abstract

Idiopathic pulmonary fibrosis is a fatal interstitial lung disease for which effective drug therapies are lacking. Senegenin, an effective active compound from the traditional Chinese herb Polygala tenuifolia Willd, has been shown to have a wide range of pharmacological effects. In this [...] Read more.

Idiopathic pulmonary fibrosis is a fatal interstitial lung disease for which effective drug therapies are lacking. Senegenin, an effective active compound from the traditional Chinese herb Polygala tenuifolia Willd, has been shown to have a wide range of pharmacological effects. In this study, we investigated the therapeutic effects of senegenin on pulmonary fibrosis and their associated mechanisms of action. We found that senegenin inhibited the senescence of epithelial cells and thus exerted anti-pulmonary-fibrosis effects by inhibiting oxidative stress. In addition, we found that senegenin promoted the expression of Sirt1 and Pgc-1α and that the antioxidative and antisenescent effects of senegenin were suppressed by specific silencing of the Sirt1 and Pgc–1α genes, respectively. Moreover, the senegenin-induced effects of antioxidation, antisenescence of epithelial cells, and antifibrosis were inhibited by treatment with Sirt1 inhibitors in vivo. Thus, the Sirt1/Pgc-1α pathway exerts its antifibrotic effect on lung fibrosis by mediating the antioxidative and antisenescent effects of senegenin. Full article

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21 pages, 1365 KiB

Open AccessArticle

Identification of New, Translatable ProtectomiRs against Myocardial Ischemia/Reperfusion Injury and Oxidative Stress: The Role of MMP/Biglycan Signaling Pathways

by Tamara Szabados, Arnold Molnár, Éva Kenyeres, Kamilla Gömöri, Judit Pipis, Bence Pósa, András Makkos, Bence Ágg, Zoltán Giricz, Péter Ferdinandy, Anikó Görbe and Péter Bencsik

Antioxidants 2024, 13(6), 674; https://doi.org/10.3390/antiox13060674 (registering DOI) - 30 May 2024

Abstract

Introduction: Ischemic conditionings (ICon) were intensively investigated and several protective signaling pathways were identified. Previously, we have shown the role of matrix metalloproteinases (MMP) in myocardial ischemia/reperfusion injury (MIRI) and the cardioprotective role of biglycan (BGN), a small leucine-rich proteoglycan in vitro. Here, [...] Read more.

Introduction: Ischemic conditionings (ICon) were intensively investigated and several protective signaling pathways were identified. Previously, we have shown the role of matrix metalloproteinases (MMP) in myocardial ischemia/reperfusion injury (MIRI) and the cardioprotective role of biglycan (BGN), a small leucine-rich proteoglycan in vitro. Here, we hypothesized that cardiac MMP and BGN signaling are involved in the protective effects of ICon. Methods: A reverse target-microRNA prediction was performed by using the miRNAtarget™ 2.0 software to identify human microRNAs with a possible regulatory effect on MMP and BGN, such as on related genes. To validate the identified 1289 miRNAs in the predicted network, we compared them to two cardioprotective miRNA omics datasets derived from pig and rat models of MIRI in the presence of ICons. Results: Among the experimentally measured miRNAs, we found 100% sequence identity to human predicted regulatory miRNAs in the case of 37 porcine and 24 rat miRNAs. Upon further analysis, 42 miRNAs were identified as MIRI-associated miRNAs, from which 24 miRNAs were counter-regulated due to ICons. Conclusions: Our findings highlight 24 miRNAs that potentially regulate cardioprotective therapeutic targets associated with MMPs and BGN in a highly translatable porcine model of acute myocardial infarction. Full article

(This article belongs to the Special Issue New Strategies in Preventing Inflammatory and/or Oxidative-Stress-Induced Damages in Ischemia–Reperfusion Injury)

21 pages, 2419 KiB

Open AccessArticle

Ozone Therapy in the Integrated Treatment of Female Dogs with Mammary Cancer: Oxidative Profile and Quality of Life

by Laís Pereira Silva, Ricardo Wagner Portela, Marília Carneiro Machado, Gisele André Baptista Canuto, João Moreira Costa-Neto, Vitor de Moraes Pina de Carvalho, Hanna Carvalho de Sá, Karine Araújo Damasceno, Vinicius Ricardo Cuña de Souza, Clarisse Simões Coelho and Alessandra Estrela-Lima

Antioxidants 2024, 13(6), 673; https://doi.org/10.3390/antiox13060673 (registering DOI) - 30 May 2024

Abstract

Considering the high frequency of malignant breast tumors, there is a growing search for new therapeutic strategies that control neoplastic growth and dissemination, combined with fewer adverse reactions. Therefore, this study evaluated the effects of ozone therapy in female dogs with mammary cancer [...] Read more.

Considering the high frequency of malignant breast tumors, there is a growing search for new therapeutic strategies that control neoplastic growth and dissemination, combined with fewer adverse reactions. Therefore, this study evaluated the effects of ozone therapy in female dogs with mammary cancer undergoing chemotherapy treatment. Twenty-five canines diagnosed with malignant mammary neoplasia were divided into two groups: one treated with carboplatin alone (n = 11) and the other with carboplatin associated with ozone therapy (n = 14). Clinical and laboratory evaluations, mastectomy, analysis of the oxidative profile based on total antioxidant capacity (TAC) and serum concentrations of malondialdehyde (MDA), survival rate, and quality of life were performed. Animals in the ozone therapy group had higher concentrations of red blood cells and platelets, significantly improving the survival rate and quality of life. Furthermore, adverse reactions were less intense and frequent in this group, which was associated with an increase in TAC and a reduction in MDA. These results indicate that the combination of carboplatin and ozone therapy represents a promising complementary treatment for female dogs with mammary cancer, as it was associated with fewer adverse reactions and a better oxidative profile. Full article

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

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18 pages, 4226 KiB

Open AccessArticle

Effects of MnTBAP on Porcine Semen Cryopreservation and Capacitation

by Eunji Kim, Il-Jeoung Yu, Joohyeong Lee and Yubyeol Jeon

Antioxidants 2024, 13(6), 672; https://doi.org/10.3390/antiox13060672 (registering DOI) - 30 May 2024

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Abstract

Antioxidants protect cellular function and structure by neutralizing the oxidative stress caused by increased reactive oxygen species (ROS) during sperm freezing. Studies on cryopreservation using various antioxidants have demonstrated encouraging results. Many studies have used antioxidants to increase the efficiency of sperm freezing [...] Read more.

Antioxidants protect cellular function and structure by neutralizing the oxidative stress caused by increased reactive oxygen species (ROS) during sperm freezing. Studies on cryopreservation using various antioxidants have demonstrated encouraging results. Many studies have used antioxidants to increase the efficiency of sperm freezing and to improve the success rate of artificial insemination and pregnancy. Manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) is a newly synthesized antioxidant with positive effects on sperm morphology and capacitation in humans, rams, and stallions. In this study, porcine semen was treated with 0, 50, 100, and 150 μM of MnTBAP based on a Tris–egg-yolk extender and frozen to determine whether MnTBAP can assist the status of sperm during cryopreservation. First, motility was assessed using the computer-assisted sperm analysis (CASA) system, with the 100 μM treatment group showing the highest motile rate (66.8%) compared with that of the other groups (control, 51.1%; 50 μM and 150 μM, 59.6%); therefore, the remaining analyses were conducted comparing the two groups (control vs. 100 μM group; p < 0.01). Second, fluorescence staining was applied to examine the control and 100 μM groups using fluorescence microscopy. The viability (41.7% vs. 62.4%) and the acrosome integrity (77.9% vs. 86.4%) differed significantly (p < 0.05). In addition, the mitochondrial membrane potential (MMP) was 46.5% vs. 51.9%; the fragmentation rate, estimated using the Sperm-sus-Halomax kit, was 63.4% vs. 57.4%; and the detected caspase activity was 30.1% vs. 22.9%. These tended to be higher in the treated group but did not differ significantly. Third, measurements using FACSLyric revealed that the 100 μM treatment group exhibited a state of elevated normal lipid arrangement within the plasma membrane and diminished levels of apoptosis and ROS (p < 0.01). We assessed the expression of genes relevant to antioxidant effectiveness using real-time RT-qPCR. Our findings indicated significant alterations in the expression levels of various mRNA species, with the exception of NOX5 (p < 0.05). Finally, the straws were dissolved and used to treat matured denuded oocytes to investigate the effect on fertilization and embryo development in vitro. The cleavage rate was (77.6% vs. 84.1%), and the blastocyst rate was 9.7% vs. 11.4% (p < 0.05). In conclusion, these results suggest that MnTBAP positively affected sperm freeze–thawing, improving the fertilization capacity, and leading to increased embryo development. Full article

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17 pages, 5073 KiB

Open AccessArticle

Empagliflozin Alleviates Carfilzomib-Induced Cardiotoxicity in Mice by Modulating Oxidative Stress, Inflammatory Response, Endoplasmic Reticulum Stress, and Autophagy

by Mina Y. George, Mohamed S. Dabour, Eman Rashad and Beshay N. Zordoky

Antioxidants 2024, 13(6), 671; https://doi.org/10.3390/antiox13060671 (registering DOI) - 30 May 2024

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Abstract

Carfilzomib is an irreversible proteasome inhibitor used for multiple myeloma patients. However, carfilzomib treatment is associated with cardiovascular complications. Empagliflozin, an Sodium Glucose Co-transporter 2 inhibitor (SGLT-2) inhibitor, is an oral antidiabetic drug with proven antioxidant and anti-inflammatory properties. The aim of the [...] Read more.

Carfilzomib is an irreversible proteasome inhibitor used for multiple myeloma patients. However, carfilzomib treatment is associated with cardiovascular complications. Empagliflozin, an Sodium Glucose Co-transporter 2 inhibitor (SGLT-2) inhibitor, is an oral antidiabetic drug with proven antioxidant and anti-inflammatory properties. The aim of the present study was to determine the cardioprotective effects of empagliflozin against carfilzomib-induced cardiotoxicity. C57BL/6 mice were randomly divided into four groups: control, empagliflozin, carfilzomib, and carfilzomib + empagliflozin. Empagliflozin prevented carfilzomib-induced cardiotoxicity by ameliorating histological alterations, CK-MB, and troponin-I. Moreover, it inhibited carfilzomib-induced oxidative damage and inflammation via its action on catalase activity, reduced glutathione levels and superoxide dismutase activity, and reduced nuclear factor-κB (p65) and cytokine levels. Mechanistically, empagliflozin abrogated endoplasmic reticulum stress induced by carfilzomib, as evidenced by the effect on the Glucose Regulated Protein-78 (GRP-78)/Activating Transcription Factor 6 (ATF6)/C/EBP homologous protein (CHOP) axis. Intriguingly, carfilzomib significantly induced autophagy, an effect that was further enhanced by empagliflozin, evidenced by increased LC3B and beclin-1 mRNA expression and reduced p62 expression. The effect of empagliflozin on apoptosis was confirmed by reduced expression of active caspase-3. Importantly, empagliflozin did not alter the cytotoxic effect of carfilzomib on human U266B1 multiple myeloma cells. our findings suggest that empagliflozin may provide a new therapeutic strategy to mitigate carfilzomib-induced cardiotoxicity in multiple myeloma patients. Full article

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

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12 pages, 1199 KiB

Open AccessArticle

The Interplay between Nitrosative Stress, Inflammation, and Antioxidant Defense in Patients with Lichen Planus

by Mircea Tampa, Ilinca Nicolae, Corina Daniela Ene, Cristina Iulia Mitran, Madalina Irina Mitran, Clara Matei and Simona Roxana Georgescu

Antioxidants 2024, 13(6), 670; https://doi.org/10.3390/antiox13060670 (registering DOI) - 30 May 2024

Viewed by 72

Abstract

Background: Lichen planus (LP) is a chronic inflammatory skin disease of unelucidated etiology. LP immunopathogenesis is mainly governed by cytotoxic T lymphocytes that mediate an immune response in basal keratinocytes, which may transform into a reservoir of antigens able to initiate an autoimmune [...] Read more.

Background: Lichen planus (LP) is a chronic inflammatory skin disease of unelucidated etiology. LP immunopathogenesis is mainly governed by cytotoxic T lymphocytes that mediate an immune response in basal keratinocytes, which may transform into a reservoir of antigens able to initiate an autoimmune reaction. However, other pathogenic pathways complement these mechanisms. Recent studies highlight the involvement of nitrosative stress in the pathogenesis of chronic inflammatory skin diseases. Current data on its role in the pathogenesis of LP are scarce. Methods: In this article, we investigated nitrosative stress in 40 cutaneous LP (CLP) patients compared to 40 healthy subjects using serum markers including nitrosative stress markers—direct nitrite, total nitrite, nitrate and symmetric dimethylarginine (SDMA), total antioxidant status (TAS), and hsCRP, a marker of inflammation, and analyzed the relationship between nitrosative stress, antioxidant defense, and inflammation to offer new insights into the role of the NO pathway in LP pathogenesis. Results: We identified significantly higher serum levels of direct nitrite, total nitrite, nitrate, SDMA and hsCRP, and significantly lower levels of TAS in CLP patients versus controls. There were significant negative correlations between the serum levels of TAS and significantl positive correlations between the serum levels of hsCRP and the analyzed nitrosative stress markers in patients with CLP. Conclusion: Our results indicate an increased level of nitrosative stress in LP patients that correlates with a pro-inflammatory status and altered antioxidant defense. Full article

(This article belongs to the Special Issue Nitric Oxide and Redox Mechanisms)

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16 pages, 11304 KiB

Open AccessArticle

Osthole Suppresses Cell Growth of Prostate Cancer by Disrupting Redox Homeostasis, Mitochondrial Function, and Regulation of tiRNA^HisGTG

by Jisoo Song, Jiyeon Ham, Gwonhwa Song and Whasun Lim

Antioxidants 2024, 13(6), 669; https://doi.org/10.3390/antiox13060669 (registering DOI) - 30 May 2024

Viewed by 77

Abstract

Prostate cancer remains a significant global health concern, posing a substantial threat to men’s well-being. Despite advancements in treatment modalities, the progression of prostate cancer still presents challenges, warranting further exploration of novel therapeutic strategies. In this study, osthole, a natural coumarin derivative, [...] Read more.

Prostate cancer remains a significant global health concern, posing a substantial threat to men’s well-being. Despite advancements in treatment modalities, the progression of prostate cancer still presents challenges, warranting further exploration of novel therapeutic strategies. In this study, osthole, a natural coumarin derivative, inhibited cell viability in cancer cells but not in the normal prostate cell line. Moreover, osthole disrupted cell cycle progression. Furthermore, osthole reduces mitochondrial respiration with mitochondrial membrane potential (ΔΨm) depolarization and reactive oxygen species (ROS) generation, indicating mitochondrial dysfunction. In particular, osthole-induced ROS generation was reduced by N-acetyl-L-cysteine (NAC) in prostate cancer. In addition, using calcium inhibitors (2-APB and ruthenium red) and endoplasmic reticulum (ER) stress inhibitor (4-PBA), we confirmed that ER stress-induced calcium overload by osthole causes mitochondrial dysfunction. Moreover, we verified that the osthole-induced upregulation of tiRNA^HisGTG expression is related to mechanisms that induce permeabilization of the mitochondrial membrane and calcium accumulation. Regarding intracellular signaling, osthole inactivated the PI3K and ERK pathways while activating the expression of the P38, JNK, ER stress, and autophagy-related proteins. In conclusion, the results suggest that osthole can be used as a therapeutic or adjuvant treatment for the management of prostate cancer. Full article

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13 pages, 2238 KiB

Open AccessArticle

Vitamin E Attenuates Red-Light-Mediated Vasodilation: The Benefits of a Mild Oxidative Stress

by Agnes Keszler, Dorothee Weihrauch, Brian Lindemer, Grant Broeckel and Nicole L. Lohr

Antioxidants 2024, 13(6), 668; https://doi.org/10.3390/antiox13060668 (registering DOI) - 29 May 2024

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Abstract

Red light (670 nm) energy controls vasodilation via the formation of a transferable endothelium-derived nitric oxide (NO)-precursor-containing substance, its intracellular traffic, and exocytosis. Here we investigated the underlying mechanistic effect of oxidative stress on light-mediated vasodilation by using pressure myography on dissected murine [...] Read more.

Red light (670 nm) energy controls vasodilation via the formation of a transferable endothelium-derived nitric oxide (NO)-precursor-containing substance, its intracellular traffic, and exocytosis. Here we investigated the underlying mechanistic effect of oxidative stress on light-mediated vasodilation by using pressure myography on dissected murine arteries and immunofluorescence on endothelial cells. Treatment with antioxidants Trolox and catalase decreased vessel dilation. In the presence of catalase, a lower number of exosomes were detected in the vessel bath. Light exposure resulted in increased cellular free radical levels. Mitochondrial reactive oxygen species were also more abundant but did not alter cellular ATP production. Red light enhanced the co-localization of late exosome marker CD63 and cellular S-nitrosoprotein to a greater extent than high glucose, suggesting that a mild oxidative stress favors the localization of NO precursor in late exosomes. Exocytosis regulating protein Rab11 was more abundant after irradiation. Our findings conclude that red-light-induced gentle oxidative stress facilitates the dilation of blood vessels, most likely through empowering the traffic of vasodilatory substances. Application of antioxidants disfavors this mechanism. Full article

(This article belongs to the Special Issue Impact of Oxidative Stress and Mitochondrial Dysfunction on the Regulation of Brain, Heart, Lung and Vascular Functions)

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28 pages, 3236 KiB

Open AccessArticle

Pitavastatin Calcium Confers Fungicidal Properties to Fluconazole by Inhibiting Ubiquinone Biosynthesis and Generating Reactive Oxygen Species

by Wanqian Li, Yanru Feng, Zhe Feng, Li Wang, Malcolm Whiteway, Hui Lu and Yuanying Jiang

Antioxidants 2024, 13(6), 667; https://doi.org/10.3390/antiox13060667 - 29 May 2024

Viewed by 164

Abstract

Fluconazole (FLC) is extensively employed for the prophylaxis and treatment of invasive fungal infections (IFIs). However, the fungistatic nature of FLC renders pathogenic fungi capable of developing tolerance towards it. Consequently, converting FLC into a fungicidal agent using adjuvants assumes significance to circumvent [...] Read more.

Fluconazole (FLC) is extensively employed for the prophylaxis and treatment of invasive fungal infections (IFIs). However, the fungistatic nature of FLC renders pathogenic fungi capable of developing tolerance towards it. Consequently, converting FLC into a fungicidal agent using adjuvants assumes significance to circumvent FLC resistance and the perpetuation of fungal infections. This drug repurposing study has successfully identified pitavastatin calcium (PIT) as a promising adjuvant for enhancing the fungicidal activity of FLC from a comprehensive library of 2372 FDA-approved drugs. PIT could render FLC fungicidal even at concentrations as low as 1 μM. The median lethal dose (LD₅₀) of PIT was determined to be 103.6 mg/kg. We have discovered that PIT achieves its synergistic effect by inhibiting the activity of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, thereby impeding ubiquinone biosynthesis, inducing reactive oxygen species (ROS) generation, triggering apoptosis, and disrupting Golgi function. We employed a Candida albicans strain that demonstrated a notable tolerance to FLC to infect mice and found that PIT effectively augmented the antifungal efficacy of FLC against IFIs. This study is an illustrative example of how FDA-approved drugs can effectively eliminate fungal tolerance to FLC. Full article

(This article belongs to the Section ROS, RNS and RSS)

21 pages, 2334 KiB

Open AccessReview

Nitric Oxide Binding Geometry in Heme-Proteins: Relevance for Signal Transduction

by Giovanna De Simone, Alessandra di Masi, Diego Sbardella, Paolo Ascenzi and Massimiliano Coletta

Antioxidants 2024, 13(6), 666; https://doi.org/10.3390/antiox13060666 - 29 May 2024

Viewed by 146

Abstract

Nitric oxide (NO) synthesis, signaling, and scavenging is associated to relevant physiological and pathological events. In all tissues and organs, NO levels and related functions are regulated at different levels, with heme proteins playing pivotal roles. Here, we focus on the structural changes [...] Read more.

Nitric oxide (NO) synthesis, signaling, and scavenging is associated to relevant physiological and pathological events. In all tissues and organs, NO levels and related functions are regulated at different levels, with heme proteins playing pivotal roles. Here, we focus on the structural changes related to the different binding modes of NO to heme-Fe(II), as well as the modulatory effects of this diatomic messenger on heme-protein functions. Specifically, the ability of heme proteins to bind NO at either the distal or proximal side of the heme and the transient interchanging of the binding site is reported. This sheds light on the regulation of O₂ supply to tissues with high metabolic activity, such as the retina, where a precise regulation of blood flow is necessary to meet the demand of nutrients. Full article

(This article belongs to the Special Issue Nitric Oxide and Redox Mechanisms)

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17 pages, 2009 KiB

Open AccessArticle

Studies on the Increasing Saltiness and Antioxidant Effects of Peanut Protein Maillard Reaction Products

by Wenjing Xing, Chunmin Ma, Yang Yu, Fenglian Chen, Chunhua Yang and Na Zhang

Antioxidants 2024, 13(6), 665; https://doi.org/10.3390/antiox13060665 - 29 May 2024

Viewed by 195

Abstract

The salt taste-enhancing and antioxidant effect of the Maillard reaction on peanut protein hydrolysates (PPH) was explored. The multi-spectroscopic and sensory analysis results showed that the Maillard reaction products (MRPs) of hexose (glucose and galactose) had slower reaction rates than those of pentose [...] Read more.

The salt taste-enhancing and antioxidant effect of the Maillard reaction on peanut protein hydrolysates (PPH) was explored. The multi-spectroscopic and sensory analysis results showed that the Maillard reaction products (MRPs) of hexose (glucose and galactose) had slower reaction rates than those of pentose (xylose and arabinose), but stronger umami and increasing saltiness effects. The Maillard reaction can improve the flavor of PPH, and the galactose-Maillard reaction product (Ga-MRP) has the best umami and salinity-enhancing effects. The measured molecular weight of Ga-MRP were all below 3000 Da, among which the molecular weights between 500–3000 Da accounted for 46.7%. The products produced during the Maillard reaction process resulted in a decrease in brightness and an increase in red value of Ga-MRP. The amino acid analysis results revealed that compared with PPH, the content of salty and umami amino acids in Ga-MRPs decreased, but their proportion in total free amino acids increased, and the content of bitter amino acids decreased. In addition, the Maillard reaction enhances the reducing ability, DPPH radical scavenging ability, and Fe²⁺ chelating ability of PPH. Therefore, the Maillard reaction product of peanut protein can be expected to be used as a substitute for salt seasoning, with excellent antioxidant properties. Full article

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19 pages, 5630 KiB

Open AccessArticle

A Novel Foodstuff Mixture Improves the Gut–Liver Axis in MASLD Mice and the Gut Microbiota in Overweight/Obese Patients

by Rebeca Rosas-Campos, Ana Soledad Sandoval-Rodríguez, Jonathan Samael Rodríguez-Sanabria, Ángel Omar Vazquéz-Esqueda, Carlos Roberto Alfaro-Martinez, Rebeca Escutia-Gutiérrez, Natali Vega-Magaña, Marcela Peña-Rodríguez, José Sergio Zepeda-Nuño, Mauricio Andrade-Marcial, Yolanda Campos-Uscanga, Luis Felipe Jave-Suárez, Arturo Santos, Eira Cerda-Reyes, Mónica Almeida-López, Erika Martínez-López, Luis Alonso Herrera and Juan Armendariz-Borunda

Antioxidants 2024, 13(6), 664; https://doi.org/10.3390/antiox13060664 - 29 May 2024

Viewed by 172

Abstract

Microbial community control is crucial for maintaining homeostasis of the gut–liver axis in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we show that supplementation with a mixture of Mexican foodstuffs (MexMix)—Opuntia ficus indica (nopal), Theobroma cacao (cocoa) and Acheta domesticus (crickets)—enriches several [...] Read more.

Microbial community control is crucial for maintaining homeostasis of the gut–liver axis in metabolic dysfunction-associated steatotic liver disease (MASLD). Here, we show that supplementation with a mixture of Mexican foodstuffs (MexMix)—Opuntia ficus indica (nopal), Theobroma cacao (cocoa) and Acheta domesticus (crickets)—enriches several beneficial taxa in MASLD mice and overweight/obese humans. Thus, MexMix induces an important prebiotic effect. In mice, a restoration of intestinal health was observed due to the increased short-chain fatty acids (SCFAs) and intestinal crypt depth, Ocln and Cldn1 expression, and decreased Il6 and Tnfa expression. MexMix significantly reduced steatosis in the mice’s liver and modified the expression of 1668 genes. By PCR, we corroborated a Tnfa and Pparg decrease, and a Cat and Sod increase. In addition, MexMix increased the hepatic NRF2 nuclear translocation and miRNA-34a, miRNA-103, and miRNA-33 decline. In overweight/obese humans, MexMix improved the body image satisfaction and reduced the fat intake. These findings indicate that this new food formulation has potential as a therapeutic approach to treat conditions associated with excessive consumption of fats and sugars. Full article

(This article belongs to the Special Issue Microbiota, Oxidative Stress and Epithelial Diseases)

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26 pages, 2486 KiB

Open AccessReview

Melatonin Interaction with Other Phytohormones in the Regulation of Abiotic Stresses in Horticultural Plants

by Shanxia Huang and Songheng Jin

Antioxidants 2024, 13(6), 663; https://doi.org/10.3390/antiox13060663 (registering DOI) - 28 May 2024

Viewed by 206

Abstract

Horticultural crops play a vital role in global food production, nutrition, and the economy. Horticultural crops are highly vulnerable to abiotic stresses. These abiotic stresses hinder plant growth and development by affecting seed germination, impairing photosynthetic activity, and damaging root development, thus leading [...] Read more.

Horticultural crops play a vital role in global food production, nutrition, and the economy. Horticultural crops are highly vulnerable to abiotic stresses. These abiotic stresses hinder plant growth and development by affecting seed germination, impairing photosynthetic activity, and damaging root development, thus leading to a decrease in fruit yield, quality, and productivity. Scientists have conducted extensive research to investigate the mechanisms of resilience and the ability to cope with environmental stresses. In contrast, the use of phytohormones to alleviate the detrimental impacts of abiotic stresses on horticulture plants has been generally recognized as an effective method. Among phytohormones, melatonin (MT) is a novel plant hormone that regulates various plants’ physiological functions such as seedling development, root system architecture, photosynthetic efficiency, balanced redox homeostasis, secondary metabolites production, accumulation of mineral nutrient uptake, and activated antioxidant defense system. Importantly, MT application significantly restricted heavy metals (HMs) uptake and increased mineral nutrient accumulation by modifying the root architecture system. In addition, MT is a naturally occurring, multifunctional, nontoxic biomolecule having antioxidant properties. Furthermore, this review described the hormonal interaction between MT and other signaling molecules in order to enhance abiotic stress tolerance in horticulture crops. This review focuses on current research advancements and prospective approaches for enhancing crop tolerance to abiotic stress. Full article

(This article belongs to the Special Issue Function, Mechanism, and Application of ROS and Phytohormones in Plants under Hostile Conditions)

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15 pages, 2469 KiB

Open AccessArticle

Purification of Phenolic Compounds from Camellia polyodonta Flower: Composition Analysis, Antioxidant Property, and Hypolipidemic Activity In Vitro and In Vivo

by Zhuoya Xiang, Li Liu, Zhou Xu, Qingbo Kong, Heng Liang, Shiling Feng, Tao Chen, Lijun Zhou, Hongyu Yang and Chunbang Ding

Antioxidants 2024, 13(6), 662; https://doi.org/10.3390/antiox13060662 - 28 May 2024

Viewed by 224

Abstract

Camellia polyodonta flowers are rich sources of phenolics and less attention has been paid to their potential biological activity. This study aims to explore the crude extracts and resulting purified fractions (CPFP-I, II, III, and IV) through compositional analysis and antioxidant and hypolipidemic [...] Read more.

Camellia polyodonta flowers are rich sources of phenolics and less attention has been paid to their potential biological activity. This study aims to explore the crude extracts and resulting purified fractions (CPFP-I, II, III, and IV) through compositional analysis and antioxidant and hypolipidemic activities in vitro and in vivo. Among four fractions, CPFP-II contained the highest total phenolic content and flavonoid content, while CPFP-III exhibited the greatest total proanthocyanidin content. Among the 14 phenolic compounds, CPFP-II displayed the highest content of procyanidin B2, B4, and C1, whereas CPFP-III contained the highest amount of 1,2,3,6-tetragalloylglucose. The DPPH, ABTS, and FRAP assessments demonstrated a consistent trend: CPFP-II > CPFP-III > CPFP-I > CPFP-IV. In vivo experiments showed that that all four fractions significantly reduced lipid levels in hyperlipidemic C. elegans (p < 0.05), with CPFP-II exhibiting the most potent effect. Furthermore, CPFP-II effectively bound to bile acids and inhibited the enzymatic activity of pancreatic lipase in vitro. Consequently, CPFP-II should be prioritized as a promising fraction for further exploration and should provide substantial support for the feasibility of the C. polyodonta flower as a natural alternative. Full article

(This article belongs to the Section Extraction and Industrial Applications of Antioxidants)

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22 pages, 10883 KiB

Open AccessArticle

Lianweng Granules Alleviate Intestinal Barrier Damage via the IL-6/STAT3/PI3K/AKT Signaling Pathway with Dampness-Heat Syndrome Diarrhea

by Jianyu Lv, Yuchen Fu, Yu Ga, Chao Han, Yimeng Fan, Yuanyuan Wei, Sijia Hao and Zhihui Hao

Antioxidants 2024, 13(6), 661; https://doi.org/10.3390/antiox13060661 - 28 May 2024

Viewed by 244

Abstract

Dampness-heat syndrome diarrhea (DHSD) is a common clinical disease with a high prevalence but still has no satisfactory therapeutic medicine, so the search for a safe and effective drug candidate is ongoing. This study aims to explore the efficacy and mechanisms of Lianweng [...] Read more.

Dampness-heat syndrome diarrhea (DHSD) is a common clinical disease with a high prevalence but still has no satisfactory therapeutic medicine, so the search for a safe and effective drug candidate is ongoing. This study aims to explore the efficacy and mechanisms of Lianweng granules (LWG) in the treatment of DHSD and to identify the blood transport components of LWG. We assessed the efficacy of LWG in DHSD by various in vivo metrics such as body weight, disease activity index (DAI), histopathologic examination, intestinal barrier function, levels of inflammatory, apoptotic biomarkers, and oxidative stress. We identified the blood components of LWG using ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS), and the resolved key components were used to explore the relevant targets. We next predicted the potential mechanisms of LWG in treating DHSD using network pharmacology and molecular docking based on the relevant targets. Finally, the mechanisms were validated in vivo using RT-qPCR, Western blotting, ELISA, and immunofluorescence and evaluated in vitro using Cell Counting Kit-8 (CCK-8), small interfering RNA, cellular enthusiasm transfer assay (CETSA), and drug affinity response target stability (DARTS). Ninety-one pharmacodynamic components of LWG enter the bloodstream and exert possible therapeutic effects. In vivo, LWG treatment improved body weight, reduced colonic injury and DAI scores, lowered inflammation, oxidative stress, and apoptosis markers, and partially restored intestinal barrier function in DHSD mice. Guided by network pharmacology and molecular docking, it is suggested that LWG may exert therapeutic effects by inhibiting IL-6/STAT3/PI3K/AKT signaling. LWG significantly decreased the expression of IL-6, p-STAT3, p-PI3K, p-AKT, and other proteins. These findings were supported by in vitro experiments, where CETSA, DARTS, and siRNA evidenced LWG’s targeting of STAT3. LWG targeted STAT3 to inhibit inflammation, oxidative stress, and apoptosis in the colon, thereby restoring the intestinal barrier function to some extent and exerting a therapeutic effect on DHSD. Full article

(This article belongs to the Special Issue Natural Antioxidants and Oxidative Stress in Livestock and Poultry)

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22 pages, 2238 KiB

Open AccessSystematic Review

The Role of Curcumin in Oral Health and Diseases: A Systematic Review

by Francesco Inchingolo, Alessio Danilo Inchingolo, Giulia Latini, Irma Trilli, Laura Ferrante, Paola Nardelli, Giuseppina Malcangi, Angelo Michele Inchingolo, Antonio Mancini, Andrea Palermo and Gianna Dipalma

Antioxidants 2024, 13(6), 660; https://doi.org/10.3390/antiox13060660 - 28 May 2024

Viewed by 387

Abstract

Curcumin (Curcumin) belongs to the polyphenol family. It is extracted by drying the root of a plant of Asian origin, belonging to the Zingiberaceae family. The best-known species is Curcumincuma Longa. Curcumin has been recognized as having great therapeutic powers since ancient [...] Read more.

Curcumin (Curcumin) belongs to the polyphenol family. It is extracted by drying the root of a plant of Asian origin, belonging to the Zingiberaceae family. The best-known species is Curcumincuma Longa. Curcumin has been recognized as having great therapeutic powers since ancient times. Studies on curcumin have since confirmed its powerful antioxidant properties, preventing both the formation of free radicals and their neutralization, having anti-inflammatory, antibacterial, immunological, and neuroprotective properties, as well as being a regulator of the intestinal microbiota with beneficial effects on the clinical manifestations of metabolic syndrome. Our study aimed to highlight how all these therapeutic aspects could benefit oral health, both preventing and improving the course of pathological processes. The effect of mouthwashes, and curcumin-based gels on the regulation of bacterial plaque and in the control of gingivitis, was largely comparable to that of using 0.20% chlorhexidine, with fewer side effects. Being a highly hydrophobic substance, it has a high permeability to cross the cell membrane. Bioavailability increases when combined with liposoluble substances (e.g., olive oil) and piperine, which improves absorption. Curcumin also has a negligible degree of toxicity, making it an excellent alternative to the use of gold standard products for oral disinfection. Full article

(This article belongs to the Special Issue Regulatory Effects of Curcumin, 2nd Edition)

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32 pages, 1944 KiB

Open AccessReview

Advance in Iron Metabolism, Oxidative Stress and Cellular Dysfunction in Experimental and Human Kidney Diseases

by Tiancheng Xie, Li Yao and Xiaogang Li

Antioxidants 2024, 13(6), 659; https://doi.org/10.3390/antiox13060659 - 27 May 2024

Viewed by 183

Abstract

Kidney diseases pose a significant global health issue, frequently resulting in the gradual decline of renal function and eventually leading to end-stage renal failure. Abnormal iron metabolism and oxidative stress-mediated cellular dysfunction facilitates the advancement of kidney diseases. Iron homeostasis is strictly regulated [...] Read more.

Kidney diseases pose a significant global health issue, frequently resulting in the gradual decline of renal function and eventually leading to end-stage renal failure. Abnormal iron metabolism and oxidative stress-mediated cellular dysfunction facilitates the advancement of kidney diseases. Iron homeostasis is strictly regulated in the body, and disturbance in this regulatory system results in abnormal iron accumulation or deficiency, both of which are associated with the pathogenesis of kidney diseases. Iron overload promotes the production of reactive oxygen species (ROS) through the Fenton reaction, resulting in oxidative damage to cellular molecules and impaired cellular function. Increased oxidative stress can also influence iron metabolism through upregulation of iron regulatory proteins and altering the expression and activity of key iron transport and storage proteins. This creates a harmful cycle in which abnormal iron metabolism and oxidative stress perpetuate each other, ultimately contributing to the advancement of kidney diseases. The crosstalk of iron metabolism and oxidative stress involves multiple signaling pathways, such as hypoxia-inducible factor (HIF) and nuclear factor erythroid 2-related factor 2 (Nrf2) pathways. This review delves into the functions and mechanisms of iron metabolism and oxidative stress, along with the intricate relationship between these two factors in the context of kidney diseases. Understanding the underlying mechanisms should help to identify potential therapeutic targets and develop novel and effective therapeutic strategies to combat the burden of kidney diseases. Full article

29 pages, 6164 KiB

Open AccessArticle

Nanoemulsions Based on Soluble Chenopodin/Alginate Complex for Colonic Delivery of Quercetin

by Arturo Intiquilla, Migdalia Arazo, Alexander Gamboa, Nelson Caro, Martin Gotteland, Alan Palomino-Calderón, Lilian Abugoch and Cristian Tapia

Antioxidants 2024, 13(6), 658; https://doi.org/10.3390/antiox13060658 - 27 May 2024

Viewed by 424

Abstract

Inflammatory bowel disease (IBD) is an autoimmune disorder caused by uncontrolled immune activation and the subsequent destruction of the colon tissue. Quercetin (Qt) is a natural antioxidant and anti-inflammatory agent proposed as an alternative to mitigate IBD. However, its use is limited by [...] Read more.

Inflammatory bowel disease (IBD) is an autoimmune disorder caused by uncontrolled immune activation and the subsequent destruction of the colon tissue. Quercetin (Qt) is a natural antioxidant and anti-inflammatory agent proposed as an alternative to mitigate IBD. However, its use is limited by its low oral bioavailability. This study aimed to develop nanoemulsions (NEs) based on a soluble chenopodin/alginate (QPA) complex and Tween 80 (T80), intended for the colonic release of Qt, activated by the pH (5.4) and bacteria present in the human colonic microbiota. NEs with different ratios of QPA/Tw80 (F1-F6) were prepared, where F4Qt (60/40) and F5Qt (70/30) showed sizes smaller than 260 nm, PDI < 0.27, and high encapsulation efficiency (>85%). The stability was evaluated under different conditions (time, temperature, pH, and NaCl). The DSC and FTIR analyses indicated hydrophobic and hydrogen bonding interactions between QPA and Qt. F4Qt and F5Qt showed the greater release of Qt in PBS1X and Krebs buffer at pH 5.4 (diseased condition), compared to the release at pH 7.4 (healthy condition) at 8 h of study. In the presence of E. coli and B. thetaiotaomicron, they triggered the more significant release of Qt (ƒ2 < 50) compared to the control (without bacteria). The NEs (without Qt) did not show cytotoxicity in HT-29 cells (cell viability > 80%) and increased the antioxidant capacity of encapsulated Qt. Therefore, these NEs are promising nanocarriers for the delivery of flavonoids to the colon to treat IBD. Full article

(This article belongs to the Special Issue Antioxidant Potential and Bioactivity of Sustainable Green Nanoparticles)

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18 pages, 2393 KiB

Open AccessArticle

Impact of a Novel Valerian Extract on Sleep Quality, Relaxation, and GABA/Serotonin Receptor Activity in a Murine Model

by Kazim Sahin, Hasan Gencoglu, Ahmet Kayhan Korkusuz, Cemal Orhan, İsmail Ertuğ Aldatmaz, Fusun Erten, Besir Er, Abhijeet Morde, Muralidhara Padigaru and Ertugrul Kilic

Antioxidants 2024, 13(6), 657; https://doi.org/10.3390/antiox13060657 - 27 May 2024

Viewed by 417

Abstract

Insomnia is a major global health issue, highlighting the need for treatments that are both effective and safe. Valerian extract, a traditional remedy for sleep problems, offers potential therapeutic options. This research examined the potential sleep-enhancing effects of VA (Valerian Pdr%2) in mice. [...] Read more.

Insomnia is a major global health issue, highlighting the need for treatments that are both effective and safe. Valerian extract, a traditional remedy for sleep problems, offers potential therapeutic options. This research examined the potential sleep-enhancing effects of VA (Valerian Pdr%2) in mice. The study evaluated sleep quality by comparing the impact of the VA extract against melatonin on brain activity, using electrocorticography (ECoG) to assess changes in brain waves. For this purpose, the study utilized two experimental models on BALB/c mice to explore the effects of caffeine-induced insomnia and pentobarbital-induced sleep. In the first model, 25 mice were assigned to five groups to test the effects of caffeine (caffeine, 7.5 mg/kg i.p) alone, caffeine with melatonin (2 mg/kg), or caffeine with different doses of valerian extract (100 or 300 mg/kg) given orally on brain activity, assessed via electrocorticography (ECoG) and further analyses on the receptor proteins and neurotransmitters. In the second model, a different set of 25 mice were divided into five groups to examine the impact of pentobarbital (42 mg/kg) alone, with melatonin, or with the valerian extract on sleep induction, observing the effects 45 min after administration. The study found that ECoG frequencies were lower in groups treated with melatonin and two doses of valerian extract (100 and 300 mg/kg), with 300 mg/kg showing the most significant effect in reducing frequencies compared to the caffeine control group, indicating enhanced sleep quality (p < 0.05). This was supported by increased levels of serotonin, melatonin, and dopamine and higher levels of certain brain receptors in the melatonin and valerian extract groups (p < 0.05). Modulatory efficacy for the apoptotic markers in the brain was also noted (p < 0.05). Additionally, melatonin and both doses of VA increased sleep duration and reduced sleep onset time compared to the pentobarbital control, which was particularly notable with high doses. In conclusion, the findings suggest that high doses (300 mg/kg) of valerian extract enhance both the quantity and quality of sleep through the GABAergic pathway and effectively increase sleep duration while reducing the time to fall asleep in a pentobarbital-induced sleep model in mice. Full article

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31 pages, 776 KiB

Open AccessReview

Cardiovascular Disease and miRNAs: Possible Oxidative Stress-Regulating Roles of miRNAs

by Seahyoung Lee

Antioxidants 2024, 13(6), 656; https://doi.org/10.3390/antiox13060656 - 27 May 2024

Viewed by 319

Abstract

MicroRNAs (miRNAs) have been highlighted as key players in numerous diseases, and accumulating evidence indicates that pathological expressions of miRNAs contribute to both the development and progression of cardiovascular diseases (CVD), as well. Another important factor affecting the development and progression of CVD [...] Read more.

MicroRNAs (miRNAs) have been highlighted as key players in numerous diseases, and accumulating evidence indicates that pathological expressions of miRNAs contribute to both the development and progression of cardiovascular diseases (CVD), as well. Another important factor affecting the development and progression of CVD is reactive oxygen species (ROS), as well as the oxidative stress they may impose on the cells. Considering miRNAs are involved in virtually every biological process, it is not unreasonable to assume that miRNAs also play critical roles in the regulation of oxidative stress. This narrative review aims to provide mechanistic insights on possible oxidative stress-regulating roles of miRNAs in cardiovascular diseases based on differentially expressed miRNAs reported in various cardiovascular diseases and their empirically validated targets that have been implicated in the regulation of oxidative stress. Full article

(This article belongs to the Special Issue Non-Coding RNAs and Reactive Oxygen Species)

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16 pages, 684 KiB

Open AccessArticle

Pseudomonas aeruginosa Activates Quorum Sensing, Antioxidant Enzymes and Type VI Secretion in Response to Oxidative Stress to Initiate Biofilm Formation and Wound Chronicity

by Jane H. Kim, Julianna Dong, Brandon H. Le, Zachery R. Lonergan, Weifeng Gu, Thomas Girke, Wei Zhang, Dianne K. Newman and Manuela Martins-Green

Antioxidants 2024, 13(6), 655; https://doi.org/10.3390/antiox13060655 - 27 May 2024

Viewed by 266

Abstract

Pseudomonas aeruginosa (PA) is an opportunistic pathogen frequently isolated from cutaneous chronic wounds. How PA, in the presence of oxidative stress (OS), colonizes chronic wounds and forms a biofilm is still unknown. The purpose of this study is to investigate [...] Read more.

Pseudomonas aeruginosa (PA) is an opportunistic pathogen frequently isolated from cutaneous chronic wounds. How PA, in the presence of oxidative stress (OS), colonizes chronic wounds and forms a biofilm is still unknown. The purpose of this study is to investigate the changes in gene expression seen when PA is challenged with the high levels of OS present in chronic wounds. We used a biofilm-forming PA strain isolated from the chronic wounds of our murine model (RPA) and performed a qPCR to obtain gene expression patterns as RPA developed a biofilm in vitro in the presence of high levels of OS, and then compared the findings in vivo, in our mouse model of chronic wounds. We found that the planktonic bacteria under OS conditions overexpressed quorum sensing genes that are important for the bacteria to communicate with each other, antioxidant stress genes important to reduce OS in the microenvironment for survival, biofilm formation genes and virulence genes. Additionally, we performed RNAseq in vivo and identified the activation of novel genes/pathways of the Type VI Secretion System (T6SS) involved in RPA pathogenicity. In conclusion, RPA appears to survive the high OS microenvironment in chronic wounds and colonizes these wounds by turning on virulence, biofilm-forming and survival genes. These findings reveal pathways that may be promising targets for new therapies aimed at disrupting PA-containing biofilms immediately after debridement to facilitate the treatment of chronic human wounds. Full article

(This article belongs to the Special Issue Oxidative Stress in Wound Healing)

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Antioxidants, Volume 13, Issue 6 (June 2024) – 64 articles

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