Antioxidants

Editorial

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6 pages, 226 KiB

Open AccessEditorial

New Mechanisms of Action of Natural Antioxidants in Health and Disease II

by Silvana Hrelia and Cristina Angeloni

Antioxidants 2021, 10(8), 1200; https://doi.org/10.3390/antiox10081200 - 27 Jul 2021

Cited by 5 | Viewed by 2030

Abstract

Epidemiological studies have demonstrated an association between natural antioxidants and human health [...] Full article

(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease II)

Research

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16 pages, 3711 KiB

Open AccessArticle

Antioxidant Properties of Alpha-Lipoic (Thioctic) Acid Treatment on Renal and Heart Parenchyma in a Rat Model of Hypertension

by Ilenia Martinelli, Daniele Tomassoni, Proshanta Roy, Lorenzo Di Cesare Mannelli, Francesco Amenta and Seyed Khosrow Tayebati

Antioxidants 2021, 10(7), 1006; https://doi.org/10.3390/antiox10071006 - 23 Jun 2021

Cited by 16 | Viewed by 2894

Abstract

Renal and cardiac impairments are frequent events in the presence of hypertension. Organ damage is mainly linked to oxidative stress due to high blood pressure and may be reduced by antioxidant supplementation. Alpha-lipoic acid (ALA) is one of most effective antioxidants. It is [...] Read more.

Renal and cardiac impairments are frequent events in the presence of hypertension. Organ damage is mainly linked to oxidative stress due to high blood pressure and may be reduced by antioxidant supplementation. Alpha-lipoic acid (ALA) is one of most effective antioxidants. It is widely used as a nutritional supplement in a racemic mixture (+/–), even though the (+)-enantiomer is biologically active. This study was designed to investigate the effect of treatment with (+/–)-ALA and its enantiomers on renal and heart parenchyma in spontaneously hypertensive rats (SHR), using immunochemical and immunohistochemical techniques. The results confirmed that the oxidative mechanisms of organ alterations, due to hypertension, and characterized by glomerular and tubular lesions, left ventricular hypertrophy, and fibrosis but not by apoptosis were accompanied by proteins’ and nucleic acids’ oxidation. We found greater effectiveness of (+)-ALA compared to (+/−)-ALA in reducing oxidative stress, cardiac and renal damages in SHR. To conclude, these data propose (+)-ALA as one of the more appropriate antioxidant molecules to prevent renal and cardiac alterations associated with hypertension. Full article

(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease II)

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16 pages, 324 KiB

Open AccessArticle

Association between Food Intake, Clinical and Metabolic Markers and DNA Damage in Older Subjects

by Cristian Del Bo’, Daniela Martini, Stefano Bernardi, Letizia Gigliotti, Mirko Marino, Giorgio Gargari, Tomas Meroño, Nicole Hidalgo-Liberona, Cristina Andres-Lacueva, Paul A. Kroon, Antonio Cherubini, Simone Guglielmetti, Marisa Porrini and Patrizia Riso

Antioxidants 2021, 10(5), 730; https://doi.org/10.3390/antiox10050730 - 06 May 2021

Cited by 4 | Viewed by 2272

Abstract

The use of DNA damage as marker of oxidative stress, metabolic dysfunction and age-related diseases is debated. The present study aimed at assessing the level of DNA damage (evaluated as DNA strand-breaks, endogenous and oxidatively-induced DNA damage) in a group of older subjects [...] Read more.

The use of DNA damage as marker of oxidative stress, metabolic dysfunction and age-related diseases is debated. The present study aimed at assessing the level of DNA damage (evaluated as DNA strand-breaks, endogenous and oxidatively-induced DNA damage) in a group of older subjects with intestinal permeability enrolled within the MaPLE (Gut and Blood Microbiomics for Studying the Effect of a Polyphenol-Rich Dietary Pattern on Intestinal Permeability in the Elderly) intervention trial, to evaluate its association with clinical, metabolic and dietary markers. DNA damage in peripheral blood mononuclear cells was assessed by the comet assay in 49 older subjects participating in the study. Clinical and metabolic markers, markers of inflammation, vascular function and intestinal permeability were determined in serum. Food intake was estimated by weighted food diaries. On the whole, a trend towards higher levels of DNA damage was observed in men compared to women (p = 0.071). A positive association between DNA damage and clinical/metabolic markers (e.g., uric acid, lipid profile) and an inverse association with dietary markers (e.g., vitamin C, E, B₆, folates) were found and differed based on sex. By considering the importance of DNA stability during aging, the results obtained on sex differences and the potential role of dietary and metabolic factors on DNA damage underline the need for further investigations in a larger group of older adults to confirm the associations found and to promote preventive strategies. Full article

(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease II)

24 pages, 2470 KiB

Open AccessArticle

Antioxidant and Neuroprotective Activity of Extra Virgin Olive Oil Extracts Obtained from Quercetano Cultivar Trees Grown in Different Areas of the Tuscany Region (Italy)

by Maria Cristina Barbalace, Lorenzo Zallocco, Daniela Beghelli, Maurizio Ronci, Serena Scortichini, Maria Digiacomo, Marco Macchia, Maria Rosa Mazzoni, Dennis Fiorini, Antonio Lucacchini, Silvana Hrelia, Laura Giusti and Cristina Angeloni

Antioxidants 2021, 10(3), 421; https://doi.org/10.3390/antiox10030421 - 10 Mar 2021

Cited by 14 | Viewed by 3103

Abstract

Neurodegenerative diseases are driven by several mechanisms such as inflammation, abnormal protein aggregation, excitotoxicity, mitochondrial dysfunction and oxidative stress. So far, no therapeutic strategies are available for neurodegenerative diseases and in recent years the research is focusing on bioactive molecules present in food. [...] Read more.

Neurodegenerative diseases are driven by several mechanisms such as inflammation, abnormal protein aggregation, excitotoxicity, mitochondrial dysfunction and oxidative stress. So far, no therapeutic strategies are available for neurodegenerative diseases and in recent years the research is focusing on bioactive molecules present in food. In particular, extra-virgin olive oil (EVOO) phenols have been associated to neuroprotection. In this study, we investigated the potential antioxidant and neuroprotective activity of two different EVOO extracts obtained from Quercetano cultivar trees grown in two different areas (plain and hill) of the Tuscany region (Italy). The different geographical origin of the orchards influenced phenol composition. Plain extract presented a higher content of phenyl ethyl alcohols, cinnammic acids, oleacein, oleocanthal and flavones; meanwhile, hill extract was richer in lignans. Hill extract was more effective in protecting differentiated SH-SY5Y cells from peroxide stress thanks to a marked upregulation of the antioxidant enzymes heme oxygenase 1, NADPH quinone oxidoreductase 1, thioredoxin Reductase 1 and glutathione reductase. Proteomic analysis revealed that hill extract plays a role in the regulation of proteins involved in neuronal plasticity and activation of neurotrophic factors such as BDNF. In conclusion, these data demonstrate that EVOOs can have important neuroprotective activities, but these effects are strictly related to their specific phenol composition. Full article

(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease II)

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21 pages, 3124 KiB

Open AccessArticle

Fermented Soy-Derived Bioactive Peptides Selected by a Molecular Docking Approach Show Antioxidant Properties Involving the Keap1/Nrf2 Pathway

by Federica Tonolo, Laura Moretto, Alessandro Grinzato, Federico Fiorese, Alessandra Folda, Valeria Scalcon, Stefania Ferro, Giorgio Arrigoni, Marco Bellamio, Emiliano Feller, Alberto Bindoli, Oriano Marin and Maria Pia Rigobello

Antioxidants 2020, 9(12), 1306; https://doi.org/10.3390/antiox9121306 - 19 Dec 2020

Cited by 44 | Viewed by 3931

Abstract

Bioactive peptides are a group of molecules with health beneficial properties, deriving from food matrices. They are protein fragments consisting of 2–20 amino acids that can be released by microbial fermentation, food processing and gastrointestinal digestion. Once hydrolyzed from their native proteins, they [...] Read more.

Bioactive peptides are a group of molecules with health beneficial properties, deriving from food matrices. They are protein fragments consisting of 2–20 amino acids that can be released by microbial fermentation, food processing and gastrointestinal digestion. Once hydrolyzed from their native proteins, they can have different functions including antioxidant activity, which is important for cell protection by oxidant agents. In this work, fermented soy products were digested in vitro in order to improve the release of bioactive peptides. These were extracted, purified and analyzed in vitro and in a cellular model to assess their antioxidant activity. Peptide sequences were identified by LC-MS/MS analysis and a molecular docking approach was used to predict their ability to interact with Keap1, one of the key proteins of the Keap1/Nrf2 pathway, the major system involved in redox regulation. Peptides showing a high score of interaction were selected and tested for their antioxidant properties in a cellular environment using the Caco-2 cell line and examined for their capability to defend cells against oxidative stress. Our results indicate that several of the selected peptides were indeed able to activate the Keap1/Nrf2 pathway with the consequent overexpression of antioxidant and phase II enzymes. Full article

(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease II)

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16 pages, 3514 KiB

Open AccessArticle

Salvia sclarea L. Essential Oil Extract and Its Antioxidative Phytochemical Sclareol Inhibit Oxytocin-Induced Uterine Hypercontraction Dysmenorrhea Model by Inhibiting the Ca²⁺–MLCK–MLC20 Signaling Cascade: An Ex Vivo and In Vivo Study

by Jennifer Wong, Yi-Fen Chiang, Yin-Hwa Shih, Chun-Hui Chiu, Hsin-Yuan Chen, Tzong-Ming Shieh, Kai-Lee Wang, Tsui-Chin Huang, Yong-Han Hong and Shih-Min Hsia

Antioxidants 2020, 9(10), 991; https://doi.org/10.3390/antiox9100991 - 14 Oct 2020

Cited by 26 | Viewed by 3952

Abstract

Salvia sclarea essential oil is used as an aromatic therapy for dysmenorrhea. Sclareol—one of the natural products isolated from S. sclarea—displays anti-inflammatory and antioxidant activities; however, researchers have not yet evaluated the mechanism related to the pain-relieving effect of sclareol. In the [...] Read more.

Salvia sclarea essential oil is used as an aromatic therapy for dysmenorrhea. Sclareol—one of the natural products isolated from S. sclarea—displays anti-inflammatory and antioxidant activities; however, researchers have not yet evaluated the mechanism related to the pain-relieving effect of sclareol. In the present study, we aimed to investigate the potential effect of sclareol in ex vivo and in vivo dysmenorrhea models, as well as its possible mechanism. In the ex vivo study of uterine tissue from Sprague Dawley (SD) rats, the uterine contraction amplitude was observed and recorded. In the in vivo study, we measured the uterine contraction pressure of SD rats and performed writhing tests on mice. The uterine tissues from the writhing test subjects were collected and analyzed by Western blot. The results demonstrated that sclareol inhibited prostaglandin (PG) F_2α-, oxytocin-, acetylcholine-, carbachol-, KCl-, and Bay K 8644-induced uterine contraction and possessed an analgesic effect in the writhing test. Sclareol affects the Ca²⁺ level and regulates oxytocin receptor (OTR), myosin light chain kinase (MLCK), extracellular signal-regulated kinase, p-p38, cyclooxygenase-2 (COX-2), and phospho-myosin light chain 20 (p-MLC20) protein expression. Integrating these results, we suggest that sclareol is a potential alternative supplement for dysmenorrhea. Full article

(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease II)

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15 pages, 3899 KiB

Open AccessArticle

Pharmacokinetics and Protective Effects of Tartary Buckwheat Flour Extracts against Ethanol-Induced Liver Injury in Rats

by Hye-Rin Jin, Suyong Lee and Soo-Jin Choi

Antioxidants 2020, 9(10), 913; https://doi.org/10.3390/antiox9100913 - 24 Sep 2020

Cited by 8 | Viewed by 3002

Abstract

The grains of Tartary buckwheat (Fagopyrum esculentum) are traditionally consumed on a daily basis and are used in the preparation of diverse processed foods owing to the high concentration of rutin, an antioxidant compound. However, rutin is highly concentrated in hull [...] Read more.

The grains of Tartary buckwheat (Fagopyrum esculentum) are traditionally consumed on a daily basis and are used in the preparation of diverse processed foods owing to the high concentration of rutin, an antioxidant compound. However, rutin is highly concentrated in hull and bran, but not in edible flour fractions. Rutin-enriched TB flour extracts (TBFEs) were obtained by hydrothermal treatment (autoclaving, boiling, or steaming) and their pharmacokinetic profiles were evaluated following a single-dose oral administration in rats. The antioxidant and protective activities of the extracts against alcoholic liver disease (ALD) were investigated after repetitive oral administration of TBFEs for 28 days prior to ethanol ingestion. The results demonstrated that rutin-enriched TBFEs had better oral absorption and was retained longer in the bloodstream than native TBFE or standard rutin. The activities of antioxidant enzymes and intracellular antioxidant levels increased in ALD rats following TBFE treatments, especially following the administration of rutin-enriched TBFEs. The antioxidant activity of TBFEs consequently contributed toward protecting the liver against injury caused by repetitive ethanol administration, as confirmed by analyzing relative liver weight, liver injury markers, lipid peroxidation, and calcium permeability. These results suggest the promising potential of TBFEs as antioxidant-enriched functional foods for human health. Full article

(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease II)

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21 pages, 4738 KiB

Open AccessArticle

Counteracting Cisplatin-Induced Testicular Damages by Natural Polyphenol Constituent Honokiol

by Tse-En Wang, Yu-Hua Lai, Kai-Chien Yang, Sung-Jan Lin, Chih-Lin Chen and Pei-Shiue Tsai

Antioxidants 2020, 9(8), 723; https://doi.org/10.3390/antiox9080723 - 09 Aug 2020

Cited by 29 | Viewed by 4282

Abstract

Cisplatin, despite its anti-cancer ability, exhibits severe testicular toxicities when applied systemically. Due to its wide application in cancer treatment, reduction of its damages to normal tissue is an imminent clinical need. Here we evaluated the effects of honokiol, a natural lipophilic polyphenol [...] Read more.

Cisplatin, despite its anti-cancer ability, exhibits severe testicular toxicities when applied systemically. Due to its wide application in cancer treatment, reduction of its damages to normal tissue is an imminent clinical need. Here we evaluated the effects of honokiol, a natural lipophilic polyphenol compound, on cisplatin-induced testicular injury. We showed in-vitro and in-vivo that nanosome-encapsulated honokiol attenuated cisplatin-induced DNA oxidative stress by suppressing intracellular reactive oxygen species production and elevating gene expressions of mitochondrial antioxidation enzymes. Nanosome honokiol also mitigated endoplasmic reticulum stress through down regulation of Bip-ATF4-CHOP signaling pathway. Additionally, this natural polyphenol compound diminished cisplatin-induced DNA breaks and cellular apoptosis. The reduced type I collagen accumulation in the testis likely attributed from inhibition of TGFβ1, αSMA and ER protein TXNDC5 protein expression. The combinatorial beneficial effects better preserve spermatogenic layers and facilitate repopulation of sperm cells. Our study renders opportunity for re-introducing cisplatin to systemic anti-cancer therapy with reduced testicular toxicity and restored fertility. Full article

(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease II)

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23 pages, 4568 KiB

Open AccessArticle

Flavonoids Identification and Pancreatic Beta-Cell Protective Effect of Lotus Seedpod

by Ming-Shih Lee, Charng-Cherng Chyau, Chi-Ping Wang, Ting-Hsuan Wang, Jing-Hsien Chen and Hui-Hsuan Lin

Antioxidants 2020, 9(8), 658; https://doi.org/10.3390/antiox9080658 - 24 Jul 2020

Cited by 14 | Viewed by 3732

Abstract

Oxidative stress is highly associated with the development of diabetes mellitus (DM), especially pancreatic beta-cell injury. Flavonoids derived from plants have caused important attention in the prevention or treatment of DM. Lotus seedpod belongs to a traditional Chinese herbal medicine and has been [...] Read more.

Oxidative stress is highly associated with the development of diabetes mellitus (DM), especially pancreatic beta-cell injury. Flavonoids derived from plants have caused important attention in the prevention or treatment of DM. Lotus seedpod belongs to a traditional Chinese herbal medicine and has been indicated to possess antioxidant, anti-age, anti-glycative, and hepatoprotective activities. The purpose of this study was to demonstrate the pancreatic beta-cell protective effects of lotus seedpod aqueous extracts (LSE) against oxidative injury. According to HPLC/ESI-MS-MS method, LSE was confirmed to have flavonoids derivatives, especially quercetin-3-glucuronide (Q3G). In vitro, LSE dose-dependently improved the survival and function of rat pancreatic beta-cells (RIN-m5F) from hydrogen peroxide (H₂O₂)-mediated loss of cell viability, impairment of insulin secretion, and promotion of oxidative stress. LSE showed potential in decreasing the H₂O₂-induced occurrence of apoptosis. In addition, H₂O₂-triggered acidic vesicular organelle formation and microtubule-associated protein light chain 3 (LC3)-II upregulation, markers of autophagy, were increased by LSE. Molecular data explored that antiapoptotic and autophagic effects of LSE, comparable to that of Q3G, might receptively be mediated via phospho-Bcl-2-associated death promoter (p-Bad)/B-cell lymphoma 2 (Bcl-2) and class III phosphatidylinositol-3 kinase (PI3K)/LC3-II signal pathway. In vivo, LSE improved the DM symptoms and pancreatic cell injury better than metformin, a drug that is routinely prescribed to treat DM. These data implied that LSE induces the autophagic signaling, leading to protect beta-cells from oxidative stress-related apoptosis and injury. Full article

(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease II)

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16 pages, 2750 KiB

Open AccessArticle

Esculetin as a Bifunctional Antioxidant Prevents and Counteracts the Oxidative Stress and Neuronal Death Induced by Amyloid Protein in SH-SY5Y Cells

by Letizia Pruccoli, Fabiana Morroni, Giulia Sita, Patrizia Hrelia and Andrea Tarozzi

Antioxidants 2020, 9(6), 551; https://doi.org/10.3390/antiox9060551 - 25 Jun 2020

Cited by 36 | Viewed by 3182

Abstract

Oxidative stress (OS) appears to be an important determinant during the different stages of progression of Alzheimer’s Disease (AD). In particular, impaired antioxidant defense mechanisms, such as the decrease of glutathione (GSH) and nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), a master [...] Read more.

Oxidative stress (OS) appears to be an important determinant during the different stages of progression of Alzheimer’s Disease (AD). In particular, impaired antioxidant defense mechanisms, such as the decrease of glutathione (GSH) and nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), a master regulator of antioxidant genes, including those for GSH, are associated with OS in the human AD brain. Among the neuropathological hallmarks of AD, the soluble oligomers of amyloid beta (A) peptides seem to promote neuronal death through mitochondrial dysfunction and OS. In this regard, bifunctional antioxidants can exert a dual neuroprotective role by scavenging reactive oxygen species (ROS) directly and concomitant induction of antioxidant genes. In this study, among natural coumarins (esculetin, scopoletin, fraxetin and daphnetin), we demonstrated the ability of esculetin (ESC) to prevent and counteract ROS formation in neuronal SH-SY5Y cells, suggesting its profile as a bifunctional antioxidant. In particular, ESC increased the resistance of the SH-SY5Y cells against OS through the activation of Nrf2 and increase of GSH. In similar experimental conditions, ESC could also protect the SH-SY5Y cells from the OS and neuronal death evoked by oligomers of A_1–42 peptides. Further, the use of the inhibitors PD98059 and LY294002 also showed that Erk1/2 and Akt signaling pathways were involved in the neuroprotection mediated by ESC. These results encourage further research in AD models to explore the efficacy and safety profile of ESC as a novel neuroprotective agent. Full article

(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease II)

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19 pages, 5655 KiB

Open AccessArticle

Ethosomes for Coenzyme Q10 Cutaneous Administration: From Design to 3D Skin Tissue Evaluation

by Maddalena Sguizzato, Paolo Mariani, Francesco Spinozzi, Mascia Benedusi, Franco Cervellati, Rita Cortesi, Markus Drechsler, Roxane Prieux, Giuseppe Valacchi and Elisabetta Esposito

Antioxidants 2020, 9(6), 485; https://doi.org/10.3390/antiox9060485 - 03 Jun 2020

Cited by 31 | Viewed by 4411

Abstract

Ethosome represents a smart transdermal vehicle suitable for solubilization and cutaneous application of drugs. Coenzyme Q10 is an endogenous antioxidant whose supplementation can counteract many cutaneous disorders and pathologies. In this respect, the present study describes the production, characterization, and cutaneous protection of [...] Read more.

Ethosome represents a smart transdermal vehicle suitable for solubilization and cutaneous application of drugs. Coenzyme Q10 is an endogenous antioxidant whose supplementation can counteract many cutaneous disorders and pathologies. In this respect, the present study describes the production, characterization, and cutaneous protection of phosphatidylcholine based ethosomes as percutaneous delivery systems for coenzyme Q10. CoQ10 entrapment capacity in ethosomes was almost 100%, vesicles showed the typical ‘fingerprint’ structure, while mean diameters were around 270 nm, undergoing an 8% increase after 3 months from production. An ex-vivo study, conducted by transmission electron microscopy, could detect the uptake of ethosomes in human skin fibroblasts and the passage of the vesicles through 3D reconstituted human epidermis. Immunofluorescence analyses were carried on both on fibroblasts and 3D reconstituted human epidermis treated with ethosomes in the presence of H₂O₂ as oxidative stress challenger, evaluating 4-hydroxynonenal protein adducts which is as a reliable biomarker for oxidative damage. Notably, the pretreatment with CoQ10 loaded in ethosomes exerted a consistent protective effect against oxidative stress, in both models, fibroblasts and in reconstituted human epidermis respectively. Full article

(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease II)

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Review

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27 pages, 2896 KiB

Open AccessReview

The Use of Antioxidants as Potential Co-Adjuvants to Treat Chronic Chagas Disease

by Edio Maldonado, Diego A. Rojas, Fabiola Urbina and Aldo Solari

Antioxidants 2021, 10(7), 1022; https://doi.org/10.3390/antiox10071022 - 25 Jun 2021

Cited by 16 | Viewed by 3030

Abstract

Chagas disease is a neglected tropical disease caused by the flagellated protozoa Trypanosome cruzi. This illness affects to almost 8–12 million people worldwide, however, is endemic to Latin American countries. It is mainly vectorially transmitted by insects of the Triatominae family, although [...] Read more.

Chagas disease is a neglected tropical disease caused by the flagellated protozoa Trypanosome cruzi. This illness affects to almost 8–12 million people worldwide, however, is endemic to Latin American countries. It is mainly vectorially transmitted by insects of the Triatominae family, although other transmission routes also exist. T. cruzi-infected cardiomyocytes at the chronic stage of the disease display severe mitochondrial dysfunction and high ROS production, leading to chronic myocardial inflammation and heart failure. Under cellular stress, cells usually can launch mitochondrial biogenesis in order to restore energy loss. Key players to begin mitochondrial biogenesis are the PGC-1 (PPARγ coactivator 1) family of transcriptional coactivators, which are activated in response to several stimuli, either by deacetylation or dephosphorylation, and in turn can serve as coactivators for the NRF (nuclear respiratory factor) family of transcription factors. The NRF family of transcriptional activators, namely NRF1 and NRF2, can activate gene expression of oxidative phosphorylation (OXPHOS) components, mitochondrial transcriptional factor (Tfam) and nuclear encoded mitochondrial proteins, leading to mitochondrial biogenesis. On the other hand, NRF2 can activate gene expression of antioxidant enzymes in response to antioxidants, oxidants, electrophile compounds, pharmaceutical and dietary compounds in a mechanism dependent on KEAP1 (Kelch-like ECH-associated protein 1). Since a definitive cure to treat Chagas disease has not been found yet; the use of antioxidants a co-adjuvant therapy has been proposed in an effort to improve mitochondrial functions, biogenesis, and the antioxidant defenses response. Those antioxidants could activate different pathways to begin mitochondrial biogenesis and/or cytoprotective antioxidant defenses. In this review we discuss the main mechanisms of mitochondrial biogenesis and the NRF2-KEAP1 activation pathway. We also reviewed the antioxidants used as co-adjuvant therapy to treat experimental Chagas disease and their action mechanisms and finish with the discussion of antioxidant therapy used in Chagas disease patients. Full article

(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease II)

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37 pages, 677 KiB

Open AccessReview

Vitamin E beyond Its Antioxidant Label

by Anca Ungurianu, Anca Zanfirescu, Georgiana Nițulescu and Denisa Margină

Antioxidants 2021, 10(5), 634; https://doi.org/10.3390/antiox10050634 - 21 Apr 2021

Cited by 47 | Viewed by 5375

Abstract

Vitamin E, comprising tocopherols and tocotrienols, is mainly known as an antioxidant. The aim of this review is to summarize the molecular mechanisms and signaling pathways linked to inflammation and malignancy modulated by its vitamers. Preclinical reports highlighted a myriad of cellular effects [...] Read more.

Vitamin E, comprising tocopherols and tocotrienols, is mainly known as an antioxidant. The aim of this review is to summarize the molecular mechanisms and signaling pathways linked to inflammation and malignancy modulated by its vitamers. Preclinical reports highlighted a myriad of cellular effects like modulating the synthesis of pro-inflammatory molecules and oxidative stress response, inhibiting the NF-κB pathway, regulating cell cycle, and apoptosis. Furthermore, animal-based models have shown that these molecules affect the activity of various enzymes and signaling pathways, such as MAPK, PI3K/Akt/mTOR, JAK/STAT, and NF-κB, acting as the underlying mechanisms of their reported anti-inflammatory, neuroprotective, and anti-cancer effects. In clinical settings, not all of these were proven, with reports varying considerably. Nonetheless, vitamin E was shown to improve redox and inflammatory status in healthy, diabetic, and metabolic syndrome subjects. The anti-cancer effects were inconsistent, with both pro- and anti-malignant being reported. Regarding its neuroprotective properties, several studies have shown protective effects suggesting vitamin E as a potential prevention and therapeutic (as adjuvant) tool. However, source and dosage greatly influence the observed effects, with bioavailability seemingly a key factor in obtaining the preferred outcome. We conclude that this group of molecules presents exciting potential for the prevention and treatment of diseases with an inflammatory, redox, or malignant component. Full article

(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease II)

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19 pages, 2060 KiB

Open AccessReview

L-Carnitine in Drosophila: A Review

by Maria Rosaria Carillo, Carla Bertapelle, Filippo Scialò, Mario Siervo, Gianrico Spagnuolo, Michele Simeone, Gianfranco Peluso and Filomena Anna Digilio

Antioxidants 2020, 9(12), 1310; https://doi.org/10.3390/antiox9121310 - 21 Dec 2020

Cited by 14 | Viewed by 5070

Abstract

L-Carnitine is an amino acid derivative that plays a key role in the metabolism of fatty acids, including the shuttling of long-chain fatty acyl CoA to fuel mitochondrial β-oxidation. In addition, L-carnitine reduces oxidative damage and plays an essential role in the maintenance [...] Read more.

L-Carnitine is an amino acid derivative that plays a key role in the metabolism of fatty acids, including the shuttling of long-chain fatty acyl CoA to fuel mitochondrial β-oxidation. In addition, L-carnitine reduces oxidative damage and plays an essential role in the maintenance of cellular energy homeostasis. L-carnitine also plays an essential role in the control of cerebral functions, and the aberrant regulation of genes involved in carnitine biosynthesis and mitochondrial carnitine transport in Drosophila models has been linked to neurodegeneration. Drosophila models of neurodegenerative diseases provide a powerful platform to both unravel the molecular pathways that contribute to neurodegeneration and identify potential therapeutic targets. Drosophila can biosynthesize L-carnitine, and its carnitine transport system is similar to the human transport system; moreover, evidence from a defective Drosophila mutant for one of the carnitine shuttle genes supports the hypothesis of the occurrence of β-oxidation in glial cells. Hence, Drosophila models could advance the understanding of the links between L-carnitine and the development of neurodegenerative disorders. This review summarizes the current knowledge on L-carnitine in Drosophila and discusses the role of the L-carnitine pathway in fly models of neurodegeneration. Full article

(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease II)

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20 pages, 745 KiB

Open AccessReview

Plant Phenolics: Bioavailability as a Key Determinant of Their Potential Health-Promoting Applications

by Patricia Cosme, Ana B. Rodríguez, Javier Espino and María Garrido

Antioxidants 2020, 9(12), 1263; https://doi.org/10.3390/antiox9121263 - 12 Dec 2020

Cited by 164 | Viewed by 10302

Abstract

Phenolic compounds are secondary metabolites widely spread throughout the plant kingdom that can be categorized as flavonoids and non-flavonoids. Interest in phenolic compounds has dramatically increased during the last decade due to their biological effects and promising therapeutic applications. In this review, we [...] Read more.

Phenolic compounds are secondary metabolites widely spread throughout the plant kingdom that can be categorized as flavonoids and non-flavonoids. Interest in phenolic compounds has dramatically increased during the last decade due to their biological effects and promising therapeutic applications. In this review, we discuss the importance of phenolic compounds’ bioavailability to accomplish their physiological functions, and highlight main factors affecting such parameter throughout metabolism of phenolics, from absorption to excretion. Besides, we give an updated overview of the health benefits of phenolic compounds, which are mainly linked to both their direct (e.g., free-radical scavenging ability) and indirect (e.g., by stimulating activity of antioxidant enzymes) antioxidant properties. Such antioxidant actions reportedly help them to prevent chronic and oxidative stress-related disorders such as cancer, cardiovascular and neurodegenerative diseases, among others. Last, we comment on development of cutting-edge delivery systems intended to improve bioavailability and enhance stability of phenolic compounds in the human body. Full article

(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease II)

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22 pages, 1479 KiB

Open AccessReview

Early Origins of Hypertension: Should Prevention Start Before Birth Using Natural Antioxidants?

by Chien-Ning Hsu and You-Lin Tain

Antioxidants 2020, 9(11), 1034; https://doi.org/10.3390/antiox9111034 - 23 Oct 2020

Cited by 29 | Viewed by 2610

Abstract

Hypertension may originate in early life. Reactive oxygen species (ROS) generated due to the exposure of adverse in utero conditions causes developmental programming of hypertension. These excessive ROS can be antagonized by molecules which are antioxidants. Prenatal use of natural antioxidants may reverse [...] Read more.

Hypertension may originate in early life. Reactive oxygen species (ROS) generated due to the exposure of adverse in utero conditions causes developmental programming of hypertension. These excessive ROS can be antagonized by molecules which are antioxidants. Prenatal use of natural antioxidants may reverse programming processes and prevent hypertension of developmental origin. In the current review, firstly we document data on the impact of oxidative stress in hypertension of developmental origin. This will be followed by effective natural antioxidants uses starting before birth to prevent hypertension of developmental origin in animal models. It will also discuss evidence for the common mechanisms underlying developmental hypertension and beneficial effects of natural antioxidant interventions used as reprogramming strategies. A better understanding of the reprogramming effects of natural antioxidants and their interactions with common mechanisms underlying developmental hypertension is essential. Therefore, pregnant mothers and their children can benefit from natural antioxidant supplementation during pregnancy in order to reduce their risk for hypertension later in life. Full article

(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease II)

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16 pages, 314 KiB

Open AccessReview

Glaucoma and Antioxidants: Review and Update

by Jose Javier Garcia-Medina, Elena Rubio-Velazquez, Maria Dolores Lopez-Bernal, Alejandro Cobo-Martinez, Vicente Zanon-Moreno, Maria Dolores Pinazo-Duran and Monica del-Rio-Vellosillo

Antioxidants 2020, 9(11), 1031; https://doi.org/10.3390/antiox9111031 - 22 Oct 2020

Cited by 36 | Viewed by 4636

Abstract

Glaucoma is a neurodegenerative disease characterised by the progressive degeneration of retinal ganglion cells. Oxidative stress has been related to the cell death in this disease. Theoretically, this deleterious consequence can be reduced by antioxidants substances. The aim of this review is to [...] Read more.

Glaucoma is a neurodegenerative disease characterised by the progressive degeneration of retinal ganglion cells. Oxidative stress has been related to the cell death in this disease. Theoretically, this deleterious consequence can be reduced by antioxidants substances. The aim of this review is to assemble the studies published in relation to antioxidant supplementation and its effects on glaucoma and to offer the reader an update on this field. With this purpose, we have included studies in animal models of glaucoma and clinical trials. Although there are variable results, supplementation with antioxidants in glaucoma may be a promising therapy in glaucoma. Full article

(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease II)

25 pages, 312 KiB

Open AccessReview

Effects of Supplementation with Natural Antioxidants on Oocytes and Preimplantation Embryos

by Maria Cristina Budani and Gian Mario Tiboni

Antioxidants 2020, 9(7), 612; https://doi.org/10.3390/antiox9070612 - 12 Jul 2020

Cited by 33 | Viewed by 4661

Abstract

For most infertile couples, in vitro fertilization (IVF) represents the only chance to conceive. Given the limited success of IVF procedures, novel approaches are continuously tested with the aim of improving IVF outcomes. Growing attention is devoted today to the potential benefit of [...] Read more.

For most infertile couples, in vitro fertilization (IVF) represents the only chance to conceive. Given the limited success of IVF procedures, novel approaches are continuously tested with the aim of improving IVF outcomes. Growing attention is devoted today to the potential benefit of natural antioxidants in the optimization of infertility treatments. This review summarizes current data in this context, focusing on both experimental studies on oocytes/embryos and clinical trials on antioxidants supplementation. Based on information gained from experimental studies, antioxidant supplementation may have beneficial effects on IVF outcomes in terms of quality and cryotolerance of in vitro produced embryos, together with positive effects on in vitro maturation oocytes and on early embryonic development. Unfortunately, from the clinical side, there is a paucity of evidence favoring the protective qualities of antioxidants. Among the antioxidants considered, coenzyme Q10 may be regarded as one of the most promising for its positive role in rescuing the oxidative stress-induced damages, but further data are needed. It is concluded that further trials are necessary to characterize the potential clinical value of antioxidants in IVF treatments. Full article

(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease II)

23 pages, 384 KiB

Open AccessReview

Update on the Effects of Antioxidants on Diabetic Retinopathy: In Vitro Experiments, Animal Studies and Clinical Trials

by Jose Javier Garcia-Medina, Elena Rubio-Velazquez, Elisa Foulquie-Moreno, Ricardo P Casaroli-Marano, Maria Dolores Pinazo-Duran, Vicente Zanon-Moreno and Monica del-Rio-Vellosillo

Antioxidants 2020, 9(6), 561; https://doi.org/10.3390/antiox9060561 - 26 Jun 2020

Cited by 39 | Viewed by 4572

Abstract

Current therapies for diabetic retinopathy (DR) incorporate blood glucose and blood pressure control, vitrectomy, photocoagulation, and intravitreal injections of anti-vascular endothelial growth factors or corticosteroids. Nonetheless, these techniques have not been demonstrated to completely stop the evolution of this disorder. The pathophysiology of [...] Read more.

Current therapies for diabetic retinopathy (DR) incorporate blood glucose and blood pressure control, vitrectomy, photocoagulation, and intravitreal injections of anti-vascular endothelial growth factors or corticosteroids. Nonetheless, these techniques have not been demonstrated to completely stop the evolution of this disorder. The pathophysiology of DR is not fully known, but there is more and more evidence indicating that oxidative stress is an important mechanism in the progression of DR. In this sense, antioxidants have been suggested as a possible therapy to reduce the complications of DR. In this review we aim to assemble updated information in relation to in vitro experiments, animal studies and clinical trials dealing with the effect of the antioxidants on DR. Full article

(This article belongs to the Special Issue New Mechanisms of Action of Natural Antioxidants in Health and Disease II)

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