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Natural Antioxidants in Human Health and Disease

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Bioactives and Nutraceuticals".

Deadline for manuscript submissions: closed (15 April 2023) | Viewed by 14594

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Special Issue Information

Dear Colleagues, 

Oxidative stress, defined as an overproduction of reactive oxygen (ROS) and nitrogen species (RNS) in cells and tissues, plays a pathogenic role in the development of several inflammatory chronic diseases, especially in the case of atherosclerosis, hypertension, obesity, diabetes, metabolic syndrome, and cancer. The increase in ROS and RNS can cause oxidative damage and tissue dysfunction due to structural damage to macromolecules, giving rise to senescent and degenerative lesions in cells. Natural compounds are a source of exogenous antioxidants possibly useful in the management of these pathologies. They have long been considered antioxidant molecules, and most of their benefits have been related to their free radical scavenging properties. Recent findings have shown that these compounds have multiple mechanisms of action in the treatment or prevention of oxidative disorders. Natural antioxidants could interact in humans with pleiotropic effects on a variety of tissues involved in stress response pathways. However, their diversity and chemical complexity mean that much remains to be understood about the mechanisms by which these compounds influence health.

This Special Issue is a collection of research and review articles on the preclinical and clinical benefits of natural antioxidants, with special interest in human health and disease. The aim of this Special Issue is to collect literature that reflects the actual state of the art and increase our knowledge of natural antioxidants and the mechanism of action in their physiological and pathophysiological role. Further, their bioavailability and biotransformation events should be considered to identify the most likely final effectors in cells and tissues.

As the Guest Editor of this Special Issue, I cordially invite researchers from all around the world to contribute by submitting original research articles, long and mini review papers, short notes, and opinions in accordance with their expertise.

Dr. María Herranz-López
Guest Editor

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Keywords

  • ROS
  • oxidative disorders
  • molecular pathways
  • inflammation
  • biotransformation

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Published Papers (8 papers)

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Research

20 pages, 3192 KiB  
Article
α-Bisabolol, a Dietary Sesquiterpene, Attenuates Doxorubicin-Induced Acute Cardiotoxicity in Rats by Inhibiting Cellular Signaling Pathways, Nrf2/Keap-1/HO-1, Akt/mTOR/GSK-3β, NF-κB/p38/MAPK, and NLRP3 Inflammasomes Regulating Oxidative Stress and Inflammatory Cascades
by Mohamed Fizur Nagoor Meeran, Seenipandi Arunachalam, Sheikh Azimullah, Dhanya Saraswathiamma, Alia Albawardi, Saeeda Almarzooqi, Niraj Kumar Jha, Sandeep Subramanya, Rami Beiram and Shreesh Ojha
Int. J. Mol. Sci. 2023, 24(18), 14013; https://doi.org/10.3390/ijms241814013 - 13 Sep 2023
Viewed by 1355
Abstract
Cancer chemotherapy with doxorubicin (DOX) may have multiorgan toxicities including cardiotoxicity, and this is one of the major limitations of its clinical use. The present study aimed to evaluate the cardioprotective role of α-Bisabolol (BSB) in DOX-induced acute cardiotoxicity in rats and the [...] Read more.
Cancer chemotherapy with doxorubicin (DOX) may have multiorgan toxicities including cardiotoxicity, and this is one of the major limitations of its clinical use. The present study aimed to evaluate the cardioprotective role of α-Bisabolol (BSB) in DOX-induced acute cardiotoxicity in rats and the underlying pharmacological and molecular mechanisms. DOX (12.5 mg/kg, single dose) was injected intraperitoneally into the rats for induction of acute cardiotoxicity. BSB was given orally to rats (25 mg/kg, p.o. twice daily) for a duration of five days. DOX administration induced cardiac dysfunction as evidenced by altered body weight, hemodynamics, and release of cardio-specific diagnostic markers. The occurrence of oxidative stress was evidenced by a significant decline in antioxidant defense along with a rise in lipid peroxidation and hyperlipidemia. Additionally, DOX also increased the levels and expression of proinflammatory cytokines and inflammatory mediators, as well as activated NF-κB/MAPK signaling in the heart, following alterations in the Nrf2/Keap-1/HO-1 and Akt/mTOR/GSK-3β signaling. DOX also perturbed NLRP3 inflammasome activation-mediated pyroptosis in the myocardium of rats. Furthermore, histopathological studies revealed cellular alterations in the myocardium. On the contrary, treatment with BSB has been observed to preserve the myocardium and restore all the cellular, molecular, and structural perturbations in the heart tissues of DOX-induced cardiotoxicity in rats. Results of the present study clearly demonstrate the protective role of BSB against DOX-induced cardiotoxicity, which is attributed to its potent antioxidant, anti-inflammatory, and antihyperlipidemic effects resulting from favorable modulation of numerous cellular signaling regulatory pathways, viz., Nrf2/Keap-1/HO-1, Akt/mTOR/GSK-3β, NF-κB/p38/MAPK, and NLRP3 inflammasomes, in countering the cascades of oxidative stress and inflammation. The observations suggest that BSB can be a promising agent or an adjuvant to limit the cardiac injury caused by DOX. Further studies including the role in tumor-bearing animals as well as regulatory toxicology are suggested. Full article
(This article belongs to the Special Issue Natural Antioxidants in Human Health and Disease)
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15 pages, 962 KiB  
Article
Kinetic Profile of Urine Metabolites after Acute Intake of a Phenolic Compounds-Rich Juice of Juçara (Euterpe edulis Mart.) and Antioxidant Capacity in Serum and Erythrocytes: A Human Study
by Alyne Lizane Cardoso, Luciane de Lira Teixeira, Neuza Mariko Aymoto Hassimotto, Sheyla de Liz Baptista, Cândice Laís Knöner Copetti, Debora Kurrler Rieger, Francilene Gracieli Kunradi Vieira, Gustavo Amadeu Micke, Luciano Vitali, Maria Alice Altenburg de Assis, Mayara Schulz, Roseane Fett, Edson Luiz da Silva and Patricia Faria Di Pietro
Int. J. Mol. Sci. 2023, 24(11), 9555; https://doi.org/10.3390/ijms24119555 - 31 May 2023
Cited by 1 | Viewed by 958
Abstract
The juçara palm tree produces a small spherical and black–purple fruit similar to açaí. It is rich in phenolic compounds, especially anthocyanins. A clinical trial evaluated the absorption and excretion of the main bioactive compounds in urine and the antioxidant capacity in serum [...] Read more.
The juçara palm tree produces a small spherical and black–purple fruit similar to açaí. It is rich in phenolic compounds, especially anthocyanins. A clinical trial evaluated the absorption and excretion of the main bioactive compounds in urine and the antioxidant capacity in serum and erythrocytes of 10 healthy subjects after juçara juice intake. Blood samples were collected before (0.0 h) and 0.5 h, 1 h, 2 h, and 4 h after a single dose (400 mL) of juçara juice, while urine was collected at baseline and 0–3 and 3–6 h after juice intake. Seven phenolic acids and conjugated phenolic acids were identified in urine deriving from the degradation of anthocyanins: protocatechuic acid, vanillic acid, vanillic acid glucuronide, hippuric acid, hydroxybenzoic acid, hydroxyphenylacetic acid, and ferulic acid derivative. In addition, kaempferol glucuronide was also found in urine as a metabolite of the parent compound in juçara juice. Juçara juice caused a decrease in the total oxidant status of serum after 0.5 h in comparison to baseline values (p < 0.05) and increased the phenolic acid metabolites excretion. This study shows the relationship between the production of metabolites of juçara juice and the total antioxidant status in human serum, indicating evidence of its antioxidant capacity. Full article
(This article belongs to the Special Issue Natural Antioxidants in Human Health and Disease)
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14 pages, 2271 KiB  
Article
Resveratrol Enhances Temozolomide Efficacy in Glioblastoma Cells through Downregulated MGMT and Negative Regulators-Related STAT3 Inactivation
by Moli Wu, Danyang Song, Hui Li, Nisar Ahmad, Hong Xu, Xiaobo Yang, Qian Wang, Xiaoxin Cheng, Sa Deng and Xiaohong Shu
Int. J. Mol. Sci. 2023, 24(11), 9453; https://doi.org/10.3390/ijms24119453 - 29 May 2023
Cited by 4 | Viewed by 1361
Abstract
Chemoresistance blunts the efficacy of temozolomide (TMZ) in the treatment of glioblastoma (GBM). Elevated levels of O6-methylguanine-DNA methyltransferase (MGMT) and activation of signal transducer and of transcription 3 (STAT3) have been reported to correlate with GBM resistance to alkylator chemotherapy. Resveratrol (Res) inhibits [...] Read more.
Chemoresistance blunts the efficacy of temozolomide (TMZ) in the treatment of glioblastoma (GBM). Elevated levels of O6-methylguanine-DNA methyltransferase (MGMT) and activation of signal transducer and of transcription 3 (STAT3) have been reported to correlate with GBM resistance to alkylator chemotherapy. Resveratrol (Res) inhibits tumor growth and improves drug chemosensitivity by targeting STAT3 signaling. Whether the combined therapy of TMZ and Res could enhance chemosensitivity against GBM cells and the underlying molecular mechanism remains to be determined. In this study, Res was found to effectively improve chemosensitivities of different GBM cells to TMZ, which was evaluated by CCK-8, flow cytometry, and cell migration assay. The combined use of Res and TMZ downregulated STAT3 activity and STAT3-regulated gene products, thus inhibited cell proliferation and migration, as well as induced apoptosis, accompanied by increased levels of its negative regulators: PIAS3, SHP1, SHP2, and SOCS3. More importantly, a combination therapy of Res and TMZ reversed TMZ resistance of LN428 cells, which could be related to decreased MGMT and STAT3 levels. Furthermore, the JAK2-specific inhibitor AG490 was used to demonstrate that a reduced MGMT level was mediated by STAT3 inactivation. Taken together, Res inhibited STAT3 signaling through modulation of PIAS3, SHP1, SHP2, and SOCS3, thereby attenuating tumor growth and increasing sensitivity to TMZ. Therefore, Res is an ideal candidate to be used in TMZ combined chemotherapy for GBM. Full article
(This article belongs to the Special Issue Natural Antioxidants in Human Health and Disease)
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9 pages, 459 KiB  
Communication
Short-Term Effect of Nutraceutical Fruit Juices on Lipid Metabolism in Patients with Acquired Hypercholesterolemia
by Diego Ardissino, Alessandro Colletti, Marzia Pellizzato, Gianna Pagliari, Francesco Di Pierro and Giancarlo Cravotto
Int. J. Mol. Sci. 2023, 24(8), 7358; https://doi.org/10.3390/ijms24087358 - 16 Apr 2023
Cited by 1 | Viewed by 1508
Abstract
The crucial role of dyslipidaemia, especially hypercholesterolemia, in the development of atherosclerosis-related cardiovascular diseases has been extensively documented in genetic, pathologic, observational and intervention studies. The European guidelines for dyslipidaemia management include the possible use of lipid-lowering nutraceuticals to support a relatively large [...] Read more.
The crucial role of dyslipidaemia, especially hypercholesterolemia, in the development of atherosclerosis-related cardiovascular diseases has been extensively documented in genetic, pathologic, observational and intervention studies. The European guidelines for dyslipidaemia management include the possible use of lipid-lowering nutraceuticals to support a relatively large number of natural compounds. In this context, we have conducted a study to investigate whether dietary supplementation with a functional nutraceutical beverage, containing a standardized polyphenolic fraction from fruit, red yeast rice, phytosterols, and berberine complexed with β-cyclodextrin, could positively affect serum lipid concentration in 14 subjects with hypercholesterolemia. After 12 weeks of treatment, dietary supplementation with this nutraceutical combination was associated with significant improvements in total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol (non-HDL-C) and apolipoprotein B, compared to baseline. Compliance was excellent and no adverse effects were reported. In conclusion, this study demonstrates that 100 mL of a functional beverage containing lipid-lowering nutraceuticals safely leads to significant improvements in serum lipids in subjects with moderate hypercholesterolemia. Future research is needed to unravel the role that the polyphenols contained in fruit extracts play in the reduction of cholesterolemia and in cardiovascular disease prevention. Full article
(This article belongs to the Special Issue Natural Antioxidants in Human Health and Disease)
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14 pages, 2987 KiB  
Article
Kaempferol Suppresses Carbon Tetrachloride-Induced Liver Damage in Rats via the MAPKs/NF-κB and AMPK/Nrf2 Signaling Pathways
by Changyong Lee, Sik Yoon and Jeon-Ok Moon
Int. J. Mol. Sci. 2023, 24(8), 6900; https://doi.org/10.3390/ijms24086900 - 7 Apr 2023
Cited by 7 | Viewed by 2100
Abstract
Oxidative stress plays a critical role in the development of liver disease, making antioxidants a promising therapeutic approach for the prevention and management of liver injuries. The aim of this study was to investigate the hepatoprotective effects of kaempferol, an antioxidant flavonoid found [...] Read more.
Oxidative stress plays a critical role in the development of liver disease, making antioxidants a promising therapeutic approach for the prevention and management of liver injuries. The aim of this study was to investigate the hepatoprotective effects of kaempferol, an antioxidant flavonoid found in various edible vegetables, and its underlying mechanism in male Sprague-Dawley rats with carbon tetrachloride (CCl4)-induced acute liver damage. Oral administration of kaempferol at doses of 5 and 10 mg/kg body weight resulted in the amelioration of CCl4-induced abnormalities in hepatic histology and serum parameters. Additionally, kaempferol decreased the levels of pro-inflammatory mediators, TNF-α and IL-1β, as well as COX-2 and iNOS. Furthermore, kaempferol suppressed nuclear factor-kappa B (NF-κB) p65 activation, as well as the phosphorylation of Akt and mitogen-activated protein kinase members (MAPKs), including extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 in CCl4-intoxicated rats. In addition, kaempferol improved the imbalanced oxidative status, as evidenced by the reduction in reactive oxygen species levels and lipid peroxidation, along with increased glutathione content in the CCl4-treated rat liver. Administering kaempferol also enhanced the activation of nuclear factor-E2-related factor (Nrf2) and heme oxygenase-1 protein, as well as the phosphorylation of AMP-activated protein kinase (AMPK). Overall, these findings suggest that kaempferol exhibits antioxidative, anti-inflammatory, and hepatoprotective effects through inhibiting the MAPK/NF-κB signaling pathway and activating the AMPK/Nrf2 signaling pathway in CCl4-intoxicated rats. Full article
(This article belongs to the Special Issue Natural Antioxidants in Human Health and Disease)
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12 pages, 1257 KiB  
Communication
Influence of Drying Temperature and Harvesting Season on Phenolic Content and Antioxidant and Antiproliferative Activities of Olive (Olea europaea) Leaf Extracts
by María Losada-Echeberría, Gustavo Naranjo, Dhafer Malouche, Amani Taamalli, Enrique Barrajón-Catalán and Vicente Micol
Int. J. Mol. Sci. 2023, 24(1), 54; https://doi.org/10.3390/ijms24010054 - 20 Dec 2022
Cited by 1 | Viewed by 1780
Abstract
Interest in plant compounds has increased, given recent evidence regarding their role in human health due to their pleiotropic effects. For example, plant bioactive compounds present in food products, including polyphenols, are associated with preventive effects in various diseases, such as cancer or [...] Read more.
Interest in plant compounds has increased, given recent evidence regarding their role in human health due to their pleiotropic effects. For example, plant bioactive compounds present in food products, including polyphenols, are associated with preventive effects in various diseases, such as cancer or inflammation. Breast and colorectal cancers are among the most commonly diagnosed cancers globally. Although appreciable advances have been made in treatments, new therapeutic approaches are still needed. Thus, in this study, up to 28 olive leaf extracts were obtained during different seasons and using different drying temperatures. The influence of these conditions on total polyphenolic content (measured using Folin–Ciocalteu assays), antioxidant activity (using Trolox Equivalent Antioxidant Capacity and Ferric Reducing Ability of Plasma assays) and antiproliferative capacity (using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, MTT assays) was tested in breast and colorectal cancer cells. Increased phenolic composition and antioxidant and antiproliferative capacity are noted in the extracts obtained from leaves harvested in autumn, followed by summer, spring and winter. Regarding drying conditions, although there is not a general trend, conditions using the highest temperatures lead to the optimal phenolic content and antioxidant and antiproliferative activities in most cases. These results confirm previously published studies and provide evidence in support of the influence of both harvesting and drying conditions on the biological activity of olive leaf extracts. Full article
(This article belongs to the Special Issue Natural Antioxidants in Human Health and Disease)
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18 pages, 4004 KiB  
Article
Punicalagin Protects against the Development of Methotrexate-Induced Hepatotoxicity in Mice via Activating Nrf2 Signaling and Decreasing Oxidative Stress, Inflammation, and Cell Death
by Alayn’ Al-marddyah A. Al-khawalde, Mohammad H. Abukhalil, Muthana M. Jghef, Manal A. Alfwuaires, Fatima S. Alaryani, Saleem H. Aladaileh, Abdulmohsen I. Algefare, Shaik Karimulla, Fawaz Alasmari, Hammad Khalifeh Aldal’in, Abdulkareem A. Alanezi and Osama Y. Althunibat
Int. J. Mol. Sci. 2022, 23(20), 12334; https://doi.org/10.3390/ijms232012334 - 15 Oct 2022
Cited by 10 | Viewed by 2163
Abstract
Despite its effectiveness in treating inflammatory diseases and various malignancies, methotrexate (MTX) is well known to cause hepatotoxicity, which involves increased oxidative stress and inflammation, limiting its clinical use. Herein, we looked into the effect of punicalagin (PU), a polyphenolic molecule having a [...] Read more.
Despite its effectiveness in treating inflammatory diseases and various malignancies, methotrexate (MTX) is well known to cause hepatotoxicity, which involves increased oxidative stress and inflammation, limiting its clinical use. Herein, we looked into the effect of punicalagin (PU), a polyphenolic molecule having a variety of health-promoting attributes, on MTX-induced hepatotoxicity in mice. PU (25 and 50 mg/kg/day) was given orally to the mice for 10 days, while a single dose of MTX (20 mg/kg) was injected intraperitoneally (i.p.) at day 7. The MTX-induced liver damage was demonstrated by remarkably higher transaminases (ALT and AST), ALP, and LDH, as well as significant histological alterations in hepatic tissues. MTX-injected mice also demonstrated increases in hepatic oxidative stress markers, including malondialdehyde (MDA) and nitric oxide (NO), with a concordant drop in glutathione (GSH) content and superoxide dismutase (SOD) and catalase (CAT) activities. PU significantly attenuated the MTX-induced serum transaminases, ALP and LDH elevations, and hepatic oxidative stress measures and boosted antioxidant defenses in the liver. Moreover, the liver of MTX-treated mice showed increases in NF-κB p65 expression, pro-inflammatory cytokine (IL-6 and TNF-α) levels, and pro-apoptotic protein (caspase-3 and Bax) expression, whereas Bcl-2 and Nrf2 expressions were reduced, which were all attenuated by PU treatment. Collectively, PU inhibits oxidative damage, inflammation, and apoptosis and upregulates Nrf2 in the liver of MTX-induced mice. Thus, these findings suggest that PU may have great therapeutic potential for the prevention of MTX-induced hepatotoxicity, pending further exploration in upcoming studies. Full article
(This article belongs to the Special Issue Natural Antioxidants in Human Health and Disease)
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17 pages, 1783 KiB  
Article
Determination of the Bioactive Effect of Custard Apple By-Products by In Vitro Assays
by Alejandro Rojas-García, Lyanne Rodríguez, María de la Luz Cádiz-Gurrea, Abigail García-Villegas, Eduardo Fuentes, María del Carmen Villegas-Aguilar, Iván Palomo, David Arráez-Román and Antonio Segura-Carretero
Int. J. Mol. Sci. 2022, 23(16), 9238; https://doi.org/10.3390/ijms23169238 - 17 Aug 2022
Cited by 10 | Viewed by 2379
Abstract
Annona cherimola fruit, known as cherimoya or custard apple, is an exotic fruit from South America but is strongly produced in Andalusia, Spain. Its by-products (seeds and peel) are recognised as important sources of antioxidants, including phenolic acids, flavonoids and procyanidins. Therefore, the [...] Read more.
Annona cherimola fruit, known as cherimoya or custard apple, is an exotic fruit from South America but is strongly produced in Andalusia, Spain. Its by-products (seeds and peel) are recognised as important sources of antioxidants, including phenolic acids, flavonoids and procyanidins. Therefore, the aim of this study was to carry out the characterization of its phenolic composition and to in vitro evaluate the bioactivity of custard apple seed and peel. Therefore, high performance liquid chromatography coupled to mass spectrometry (HPLC-ESI-qTOF-MS) was performed in order to tentatively identify their phenolic composition. In the end, 19 compounds were identified and quantified, some of them for the first time in the custard apple matrix. Then, seed and peel total phenolic content, as well as antioxidant properties, radical scavenging capacity (O2, NO, HOCl) and inhibition of enzymes involved in different pathologies (hyaluronidase, elastase, collagenase, tyrosinase, acetylcholinesterase and xanthine oxidase), were evaluated. Although both extracts showed almost similar antioxidant capacities, custard apple seed stood out slightly more than peel (171 ± 2 vs. 130.0 ± 0.4 μmol TE/g DE, resp.), especially as ·NO scavenger (IC50 1.5 ± 0.2 vs. 11.8 ± 0.3 mg/L, resp.) and hyaluronidase inhibitor (IC50 170 ± 10 vs. 460 ± 20mg/L, resp.). Finally, the application of extracts on a real human model of platelet aggregation was performed, reporting antiaggregatory effects in agonist-promoted platelet thrombus formation. All these results show that custard apple by-products are stated as interesting sources of bioactive compounds with multiple industrial applications for the development of high-added-value products, such as functional foods, nutraceuticals and cosmeceuticals, promoting the circular bioeconomy of these by-products. Full article
(This article belongs to the Special Issue Natural Antioxidants in Human Health and Disease)
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