Advances in the Astonishing World of Phytochemicals: State-of-the-Art for Antioxidants

A special issue of Antioxidants (ISSN 2076-3921). This special issue belongs to the section "Natural and Synthetic Antioxidants".

Deadline for manuscript submissions: closed (15 July 2023) | Viewed by 41010

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Laboratory of Biochemistry, Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, 90127 Palermo, Italy
Interests: biochemical pathways in cancer cell death (apoptosis, necrosis, necroptosis, autophagy and anoikis); nutrition and human diseases; oxidative stress; signal transduction; targeted therapies; cancer stem-like cells; analysis of the behaviours of phytocompounds in obesity treatment
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Dear Colleagues,

Several studies have shown that plants are a source of a plethora of bioactive compounds, such as phytohormones, glycosides, terpenoids, alkaloids, phenolic compounds, and essential oils, with a strong potential impact in the fields of pharmaceutics and agriculture. These phytochemicals represent a valuable weapon that plants use in self-defense to counteract the abiotic stress disturbing the delicate equilibrium between the generation of reactive oxygen species (ROS) and antioxidant defense systems.

In recent years, interest in this area of research has been increasing due to the multifaceted properties of natural compounds with antioxidants having anticancer, anti-inflammatory, and antimicrobial activity. Therefore, understanding the underlying mechanism of their action is crucial to establishing their real potential in applied sciences.

We invite investigators to propose reviews or original research articles concerning the most recent advances in the study of antioxidant molecular mechanisms able to be activated by plant-derived phytochemicals, with potential pharmacological and agricultural applications.

Potential topics include, but are not limited to:

  • Antioxidant properties;
  • Antioxidant mechanisms of action;
  • Antioxidant and anticancer action;
  • Antioxidant and antimicrobial properties;
  • Antioxidant and anti-inflammatory action.

Please note that in studies of complex mixtures of natural products, the characterization of chemicals using analytical methodologies, such as HPLC, MS, LC–MS, HPLC–MS, and NMR, should be included.

Dr. Antonella D'Anneo
Dr. Marianna Lauricella
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bioactive compounds
  • phytochemicals
  • antioxidant properties
  • oxidative and nitrosative stress
  • anticancer action
  • antimicrobial properties
  • anti-inflammatory actions

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Published Papers (18 papers)

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Editorial

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6 pages, 223 KiB  
Editorial
Advances in the Astonishing World of Phytochemicals: State-of-the-Art for Antioxidants
by Marianna Lauricella and Antonella D’Anneo
Antioxidants 2023, 12(8), 1581; https://doi.org/10.3390/antiox12081581 - 08 Aug 2023
Viewed by 835
Abstract
In recent years, research on phytochemicals has underscored pleiotropic actions and medicinal and health-promoting properties which certainly deserve serious attention [...] Full article

Research

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23 pages, 6215 KiB  
Article
A Deadly Liaison between Oxidative Injury and p53 Drives Methyl-Gallate-Induced Autophagy and Apoptosis in HCT116 Colon Cancer Cells
by Antonietta Notaro, Marianna Lauricella, Diana Di Liberto, Sonia Emanuele, Michela Giuliano, Alessandro Attanzio, Luisa Tesoriere, Daniela Carlisi, Mario Allegra, Anna De Blasio, Giuseppe Calvaruso and Antonella D’Anneo
Antioxidants 2023, 12(6), 1292; https://doi.org/10.3390/antiox12061292 - 16 Jun 2023
Cited by 4 | Viewed by 1468
Abstract
Methyl gallate (MG), which is a gallotannin widely found in plants, is a polyphenol used in traditional Chinese phytotherapy to alleviate several cancer symptoms. Our studies provided evidence that MG is capable of reducing the viability of HCT116 colon cancer cells, while it [...] Read more.
Methyl gallate (MG), which is a gallotannin widely found in plants, is a polyphenol used in traditional Chinese phytotherapy to alleviate several cancer symptoms. Our studies provided evidence that MG is capable of reducing the viability of HCT116 colon cancer cells, while it was found to be ineffective on differentiated Caco-2 cells, which is a model of polarized colon cells. In the first phase of treatment, MG promoted both early ROS generation and endoplasmic reticulum (ER) stress, sustained by elevated PERK, Grp78 and CHOP expression levels, as well as an upregulation in intracellular calcium content. Such events were accompanied by an autophagic process (16–24 h), where prolonging the time (48 h) of MG exposure led to cellular homeostasis collapse and apoptotic cell death with DNA fragmentation and p53 and γH2Ax activation. Our data demonstrated that a crucial role in the MG-induced mechanism is played by p53. Its level, which increased precociously (4 h) in MG-treated cells, was tightly intertwined with oxidative injury. Indeed, the addition of N-acetylcysteine (NAC), which is a ROS scavenger, counteracted the p53 increase, as well as the MG effect on cell viability. Moreover, MG promoted p53 accumulation into the nucleus and its inhibition by pifithrin-α (PFT-α), which is a negative modulator of p53 transcriptional activity, enhanced autophagy, increased the LC3-II level and inhibited apoptotic cell death. These findings provide new clues to the potential action of MG as a possible anti-tumor phytomolecule for colon cancer treatment. Full article
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31 pages, 6619 KiB  
Article
Romanian Wild-Growing Armoracia rusticana L.—Untargeted Low-Molecular Metabolomic Approach to a Potential Antitumoral Phyto-Carrier System Based on Kaolinite
by Adina-Elena Segneanu, Gabriela Vlase, Liviu Chirigiu, Daniel Dumitru Herea, Maria-Alexandra Pricop, Patricia-Aida Saracin and Ștefania Eliza Tanasie
Antioxidants 2023, 12(6), 1268; https://doi.org/10.3390/antiox12061268 - 13 Jun 2023
Cited by 1 | Viewed by 1197
Abstract
Horseradish is a globally well-known and appreciated medicinal and aromatic plant. The health benefits of this plant have been appreciated in traditional European medicine since ancient times. Various studies have investigated the remarkable phytotherapeutic properties of horseradish and its aromatic profile. However, relatively [...] Read more.
Horseradish is a globally well-known and appreciated medicinal and aromatic plant. The health benefits of this plant have been appreciated in traditional European medicine since ancient times. Various studies have investigated the remarkable phytotherapeutic properties of horseradish and its aromatic profile. However, relatively few studies have been conducted on Romanian horseradish, and they mainly refer to the ethnomedicinal or dietary uses of the plant. This study reports the first complete low-molecular-weight metabolite profile of Romanian wild-grown horseradish. A total of ninety metabolites were identified in mass spectra (MS)-positive mode from nine secondary metabolite categories (glucosilates, fatty acids, isothiocyanates, amino acids, phenolic acids, flavonoids, terpenoids, coumarins, and miscellaneous). In addition, the biological activity of each class of phytoconstituents was discussed. Furthermore, the development of a simple target phyto-carrier system that collectively exploits the bioactive properties of horseradish and kaolinite is reported. An extensive characterization (FT-IR, XRD, DLS, SEM, EDS, and zeta potential) was performed to investigate the morpho-structural properties of this new phyto-carrier system. The antioxidant activity was evaluated using a combination of three in vitro, non-competitive methods (total phenolic assay, 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical-scavenging assay, and phosphomolybdate (total antioxidant capacity)). The antioxidant assessment indicated the stronger antioxidant properties of the new phyto-carrier system compared with its components (horseradish and kaolinite). The collective results are relevant to the theoretical development of novel antioxidant agent fields with potential applications on antitumoral therapeutic platforms. Full article
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20 pages, 8263 KiB  
Article
“Golden” Tomato Consumption Ameliorates Metabolic Syndrome: A Focus on the Redox Balance in the High-Fat-Diet-Fed Rat
by Giuditta Gambino, Giuseppe Giglia, Mario Allegra, Valentina Di Liberto, Francesco Paolo Zummo, Francesca Rappa, Ignazio Restivo, Filippo Vetrano, Filippo Saiano, Eristanna Palazzolo, Giuseppe Avellone, Giuseppe Ferraro, Pierangelo Sardo and Danila Di Majo
Antioxidants 2023, 12(5), 1121; https://doi.org/10.3390/antiox12051121 - 18 May 2023
Cited by 3 | Viewed by 1949
Abstract
Tomato fruits defined as “golden” refer to a food product harvested at an incomplete ripening stage with respect to red tomatoes at full maturation. The aim of this study is to explore the putative influence of “golden tomato” (GT) on Metabolic Syndrome (MetS), [...] Read more.
Tomato fruits defined as “golden” refer to a food product harvested at an incomplete ripening stage with respect to red tomatoes at full maturation. The aim of this study is to explore the putative influence of “golden tomato” (GT) on Metabolic Syndrome (MetS), especially focusing on the effects on redox homeostasis. Firstly, the differential chemical properties of the GT food matrix were characterized in terms of phytonutrient composition and antioxidant capacities with respect to red tomato (RT). Later, we assessed the biochemical, nutraceutical and eventually disease-modifying potential of GT in vivo in the high-fat-diet rat model of MetS. Our data revealed that GT oral supplementation is able to counterbalance MetS-induced biometric and metabolic modifications. Noteworthy is that this nutritional supplementation proved to reduce plasma oxidant status and improve the endogenous antioxidant barriers, assessed by strong systemic biomarkers. Furthermore, consistently with the reduction of hepatic reactive oxygen and nitrogen species (RONS) levels, treatment with GT markedly reduced the HFD-induced increase in hepatic lipid peroxidation and hepatic steatosis. This research elucidates the importance of food supplementation with GT in the prevention and management of MetS. Full article
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25 pages, 3470 KiB  
Article
Echinacea purpurea Fractions Represent Promising Plant-Based Anti-Inflammatory Formulations
by Sara F. Vieira, Samuel M. Gonçalves, Virgínia M. F. Gonçalves, Carmen P. Llaguno, Felipe Macías, Maria Elizabeth Tiritan, Cristina Cunha, Agostinho Carvalho, Rui L. Reis, Helena Ferreira and Nuno M. Neves
Antioxidants 2023, 12(2), 425; https://doi.org/10.3390/antiox12020425 - 09 Feb 2023
Cited by 6 | Viewed by 2367
Abstract
Echinacea purpurea is traditionally used in the treatment of inflammatory diseases. Therefore, we investigated the anti-inflammatory capacity of E. purpurea dichloromethanolic (DE) and ethanolic extracts obtained from flowers and roots (R). To identify the class of compounds responsible for the strongest bioactivity, the [...] Read more.
Echinacea purpurea is traditionally used in the treatment of inflammatory diseases. Therefore, we investigated the anti-inflammatory capacity of E. purpurea dichloromethanolic (DE) and ethanolic extracts obtained from flowers and roots (R). To identify the class of compounds responsible for the strongest bioactivity, the extracts were fractionated into phenol/carboxylic acid (F1) and alkylamide fraction (F2). The chemical fingerprint of bioactive compounds in the fractions was evaluated by LC-HRMS. E. purpurea extracts and fractions significantly reduced pro-inflammatory cytokines (interleukin 6 and/or tumor necrosis factor) and reactive oxygen and nitrogen species (ROS/RNS) production by lipopolysaccharide-stimulated primary human monocyte-derived macrophages. Dichloromethanolic extract obtained from roots (DE-R) demonstrated the strongest anti-inflammatory activity. Moreover, fractions exhibited greater anti-inflammatory activity than whole extract. Indeed, alkylamides must be the main compounds responsible for the anti-inflammatory activity of extracts; thus, the fractions presenting high content of these compounds presented greater bioactivity. It was demonstrated that alkylamides exert their anti-inflammatory activity through the downregulation of the phosphorylation of p38, ERK 1/2, STAT 3, and/or NF-κB signaling pathways, and/or downregulation of cyclooxygenase 2 expression. E. purpurea extracts and fractions, mainly DE-R-F2, are promising and powerful plant-based anti-inflammatory formulations that can be further used as a basis for the treatment of inflammatory diseases. Full article
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12 pages, 2602 KiB  
Article
Shedding Light on the Hidden Benefit of Porphyridium cruentum Culture
by Davide Liberti, Paola Imbimbo, Enrica Giustino, Luigi D’Elia, Mélanie Silva, Luísa Barreira and Daria Maria Monti
Antioxidants 2023, 12(2), 337; https://doi.org/10.3390/antiox12020337 - 31 Jan 2023
Cited by 7 | Viewed by 1721
Abstract
Microalgae can represent a reliable source of natural compounds with different activities. Here, we evaluated the antioxidant and anti-inflammatory activity of sulfated exopolysaccharides (s-EPSs) and phycoerythrin (PE), two molecules naturally produced by the red marine microalga Porphyridium cruentum (CCALA415). In vitro and cell-based [...] Read more.
Microalgae can represent a reliable source of natural compounds with different activities. Here, we evaluated the antioxidant and anti-inflammatory activity of sulfated exopolysaccharides (s-EPSs) and phycoerythrin (PE), two molecules naturally produced by the red marine microalga Porphyridium cruentum (CCALA415). In vitro and cell-based assays were performed to assess the biological activities of these compounds. The s-EPSs, owing to the presence of sulfate groups, showed biocompatibility on immortalized eukaryotic cell lines and a high antioxidant activity on cell-based systems. PE showed powerful antioxidant activity both in vitro and on cell-based systems, but purification is mandatory for its safe use. Finally, both molecules showed anti-inflammatory activity comparable to that of ibuprofen and helped tissue regeneration. Thus, the isolated molecules from microalgae represent an excellent source of antioxidants to be used in different fields. Full article
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27 pages, 2192 KiB  
Article
Antioxidant, Alpha-Glucosidase Inhibition Activities, In Silico Molecular Docking and Pharmacokinetics Study of Phenolic Compounds from Native Australian Fruits and Spices
by Akhtar Ali, Jeremy J. Cottrell and Frank R. Dunshea
Antioxidants 2023, 12(2), 254; https://doi.org/10.3390/antiox12020254 - 23 Jan 2023
Cited by 21 | Viewed by 3204
Abstract
Native Australian fruits and spices are enriched with beneficial phytochemicals, especially phenolic compounds, which are not fully elucidated. Therefore, this study aimed to analyze native Australian mountain-pepper berries (Tasmannia lanceolata), rosella (Hibiscus sabdariffa), lemon aspen (Acronychia acidula), [...] Read more.
Native Australian fruits and spices are enriched with beneficial phytochemicals, especially phenolic compounds, which are not fully elucidated. Therefore, this study aimed to analyze native Australian mountain-pepper berries (Tasmannia lanceolata), rosella (Hibiscus sabdariffa), lemon aspen (Acronychia acidula), and strawberry gum (Eucalyptus olida) for phenolic and non-phenolic metabolites and their antioxidant and alpha-glucosidase inhibition activities. Liquid chromatography–mass spectrometry–electrospray ionization coupled with quadrupole time of flight (LC-ESI-QTOF-MS/MS) was applied to elucidate the composition, identities, and quantities of bioactive phenolic metabolites in Australian native commercial fruits and spices. This study identified 143 phenolic compounds, including 31 phenolic acids, 70 flavonoids, 10 isoflavonoids, 7 tannins, 3 stilbenes, 7 lignans, 10 other compounds, and 5 limonoids. Strawberry gum was found to have the highest total phenolic content (TPC—36.57 ± 1.34 milligram gallic acid equivalent per gram (mg GAE/g), whereas lemon aspen contained the least TPC (4.40 ± 0.38 mg GAE/g). Moreover, strawberry gum and mountain pepper berries were found to have the highest antioxidant and anti-diabetic potential. In silico molecular docking and pharmacokinetics screening were also conducted to predict the potential of the most abundant phenolic compounds in these selected plants. A positive correlation was observed between phenolic contents and biological activities. This study will encourage further research to identify the nutraceutical and phytopharmaceutical potential of these native Australian fruits. Full article
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21 pages, 1602 KiB  
Article
Assessment of Gnaphalium viscosum (Kunth) Valorization Prospects: Sustainable Recovery of Antioxidants by Different Techniques
by Stanislava Boyadzhieva, Jose A. P. Coelho, Massimiliano Errico, H. Elizabeth Reynel-Avilla, Dragomir S. Yankov, Adrian Bonilla-Petriciolet and Roumiana P. Stateva
Antioxidants 2022, 11(12), 2495; https://doi.org/10.3390/antiox11122495 - 19 Dec 2022
Cited by 4 | Viewed by 1453
Abstract
This work investigates the prospects for exploitation of Gnaphalium viscosum (Kunth) abundant but with limited applications till present biomass. The feasibility of traditional techniques (two-phase solvent, and the benchmark Soxhlet extraction) and supercritical extraction without/with a cosolvent at T = 40–60 °C and [...] Read more.
This work investigates the prospects for exploitation of Gnaphalium viscosum (Kunth) abundant but with limited applications till present biomass. The feasibility of traditional techniques (two-phase solvent, and the benchmark Soxhlet extraction) and supercritical extraction without/with a cosolvent at T = 40–60 °C and p = 30–50 MPa was examined to explore the possibility of recovering phytochemicals from G. viscosum leaves, flowers and stems. The efficiency of the techniques was assessed and compared based on yield, influence of solvents used, total phenolic content and antioxidant activity of the extracts. Phenolics of different complexities were identified and quantified by applying LC (LC–MS/MS, and LC–HRAM), while the fatty acid profile was determined by GC–FID. The results of this extensive study demonstrated the huge valorization potential and prospects of G. viscosum, since highly potent antioxidants such as kaempferol, kaempferol-3-O-β-d-glucoside (astragalin), and chlorogenic acid were ascertained in considerable amounts. Furthermore, for the first time, the presence of leontopodic acid, a greatly substituted derivative of glucaric acid, was detected in the species. Full article
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20 pages, 2607 KiB  
Article
Salt Eustress Induction in Red Amaranth (Amaranthus gangeticus) Augments Nutritional, Phenolic Acids and Antiradical Potential of Leaves
by Umakanta Sarker and Sezai Ercisli
Antioxidants 2022, 11(12), 2434; https://doi.org/10.3390/antiox11122434 - 09 Dec 2022
Cited by 27 | Viewed by 2639
Abstract
Earlier researchers have highlighted the utilization of salt eustress for boosting the nutritional and phenolic acid (PA) profiles and antiradical potential (ARP) of vegetables, which eventually boost food values for nourishing human diets. Amaranth is a rapidly grown, diversely acclimated C4 leafy [...] Read more.
Earlier researchers have highlighted the utilization of salt eustress for boosting the nutritional and phenolic acid (PA) profiles and antiradical potential (ARP) of vegetables, which eventually boost food values for nourishing human diets. Amaranth is a rapidly grown, diversely acclimated C4 leafy vegetable with climate resilience and salinity resistance. The application of salinity eustress in amaranth has a great scope to augment the nutritional and PA profiles and ARP. Therefore, the A. gangeticus genotype was evaluated in response to salt eustress for nutrients, PA profile, and ARP. Antioxidant potential and high-yielding genotype (LS1) were grown under four salt eustresses (control, 25 mM, 50 mM, 100 mM NaCl) in a randomized completely block design (RCBD) in four replicates. Salt stress remarkably augmented microelements, proximate, macro-elements, phytochemicals, PA profiles, and ARP of A. gangeticus leaves in this order: control < low sodium chloride stress (LSCS) < moderate sodium chloride stress (MSCS) < severe sodium chloride stress (SSCS). A large quantity of 16 PAs, including seven cinnamic acids (CAs) and nine benzoic acids (BAs) were detected in A. gangeticus genotypes. All the microelements, proximate, macro-elements, phytochemicals, PA profiles, and ARP of A. gangeticus under MSCS, and SSCS levels were much higher in comparison with the control. It can be utilized as preferential food for our daily diets as these antiradical compounds have strong antioxidants. Salt-treated A. gangeticus contributed to excellent quality in the end product in terms of microelements, proximate, macro-elements, phytochemicals, PA profiles, and ARP. A. gangeticus can be cultivated as an encouraging substitute crop in salt-affected areas of the world. Full article
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0 pages, 645 KiB  
Article
Antioxidant, Anti-Inflammatory, and Antibacterial Properties of an Achillea millefolium L. Extract and Its Fractions Obtained by Supercritical Anti-Solvent Fractionation against Helicobacter pylori
by Marisol Villalva, Jose Manuel Silvan, Teresa Alarcón-Cavero, David Villanueva-Bermejo, Laura Jaime, Susana Santoyo and Adolfo J. Martinez-Rodriguez
Antioxidants 2022, 11(10), 1849; https://doi.org/10.3390/antiox11101849 - 20 Sep 2022
Cited by 11 | Viewed by 2660 | Correction
Abstract
The main objective of this work is to evaluate the potential utility of an Achillea millefolium extract (yarrow extract, YE) in the control of H. pylori infection. The supercritical anti-solvent fractionation (SAF) process of YE allowed the obtaining of two different fractions: yarrow’s [...] Read more.
The main objective of this work is to evaluate the potential utility of an Achillea millefolium extract (yarrow extract, YE) in the control of H. pylori infection. The supercritical anti-solvent fractionation (SAF) process of YE allowed the obtaining of two different fractions: yarrow’s precipitated fraction (YPF), enriched in most polar phenolic compounds (luteolin-7-O-glucoside, luteolin, and 3,5-dicaffeoylquinic acid), and yarrow’s separator fraction (YSF), enriched in monoterpenes and sesquiterpenes, mainly containing camphor, artemisia ketone, and borneol. YE was effective in reducing reactive oxygen species (ROS) production in human gastric AGS cells by 16% to 29%, depending on the H. pylori strain. YPF had the highest inhibitory activity (38–40%) for ROS production. YE modulated the inflammatory response in AGS gastric cells, decreasing IL-8 production by 53% to 64%. This IL-8 inhibition also showed a strain-dependent character. YPF and YSF exhibited similar behavior, reducing IL-8 production, suggesting that both phenolic compounds and essential oils could contribute to IL-8 inhibition. YSF showed the highest antibacterial activity against H. pylori (6.3–7.1 log CFU reduction, depending on the strain) and lower MIC (0.08 mg/mL). Results obtained have shown that YE and SAF fractions (YPF and YSF) were effective as antioxidant, anti-inflammatory, and antibacterial agents regardless of the H. pylori strain characteristics. Full article
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15 pages, 932 KiB  
Article
Investigation of Antioxidant Synergisms and Antagonisms among Phenolic Acids in the Model Matrices Using FRAP and ORAC Methods
by Danijela Skroza, Vida Šimat, Lucija Vrdoljak, Nina Jolić, Anica Skelin, Martina Čagalj, Roberta Frleta and Ivana Generalić Mekinić
Antioxidants 2022, 11(9), 1784; https://doi.org/10.3390/antiox11091784 - 09 Sep 2022
Cited by 31 | Viewed by 3177
Abstract
The total antioxidant potential of a sample cannot be predicted from the antioxidant activity of its compounds; thus, scientists usually explain the overall activity through their combined effects (synergistic, antagonistic, or additive). Phenolic compounds are one of the most powerful and widely investigated [...] Read more.
The total antioxidant potential of a sample cannot be predicted from the antioxidant activity of its compounds; thus, scientists usually explain the overall activity through their combined effects (synergistic, antagonistic, or additive). Phenolic compounds are one of the most powerful and widely investigated antioxidants, but there is a lack of information about their molecular interactions. This study aimed to investigate the individual and combined antioxidant activity of equimolar mixtures (binary, ternary, quaternary, and quinary) of 10 phenolic acids (protocatechuic, gentisic, gallic, vanillic, syringic, p-coumaric, caffeic, ferulic, sinapic, and rosmarinic acid) at different concentrations using ferric reducing antioxidant power (FRAP) and oxygen radical absorbance capacity (ORAC) assays. Gallic acid showed the highest antioxidant activity, determined using the FRAP assay (494–5033 µM Fe2+) and rosmarinic acid with the ORAC assay (50–92 µM Trolox Equivalents (TE)), while the lowest antioxidant potential was observed for p-coumaric acid (FRAP 24–113 µM Fe2+ and ORAC 20–33 µM TE). The synergistic effect (by FRAP) in the equimolar mixtures of hydroxybenzoic acids was confirmed for a large number of tested mixtures, especially at low concentrations. All mixtures containing gentisic acid showed a synergistic effect (28–89% difference). Using the ORAC method, only two mixtures of hydroxybenzoic acids showed an antagonistic effect, namely a mixture of gentisic + syringic acids (−24% difference) and gallic + vanillic acids (−30% difference), while all other mixtures showed a synergistic effect in a range of 26–236% difference. Among mixtures of hydroxycinnamic acids, the highest synergistic effect was observed for the mixtures of p-coumaric + ferulic acids and caffeic + sinapic acids with differences of 311% and 211%, respectively. The overall antioxidant activity of phenolic acids could be explained by the number or position of hydroxyl and/or methoxy functional groups as well as the compound concentration, but the influence of other parameters such as dissociation, intramolecular hydrogen bonds, and electron donating or withdrawing effect should not be neglected. Full article
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17 pages, 1839 KiB  
Article
Dryopteris juxtapostia Root and Shoot: Determination of Phytochemicals; Antioxidant, Anti-Inflammatory, and Hepatoprotective Effects; and Toxicity Assessment
by Abida Rani, Muhammad Uzair, Shehbaz Ali, Muhammad Qamar, Naveed Ahmad, Malik Waseem Abbas and Tuba Esatbeyoglu
Antioxidants 2022, 11(9), 1670; https://doi.org/10.3390/antiox11091670 - 27 Aug 2022
Cited by 9 | Viewed by 2148
Abstract
An estimated 450 species of Dryopteris in the Dryoperidaceae family grow in Japan, North and South Korea, China, Pakistan, and Kashmir. This genus has been reported to have biological capabilities; however, research has been conducted on Dryopteris juxtapostia. Therefore, with the present [...] Read more.
An estimated 450 species of Dryopteris in the Dryoperidaceae family grow in Japan, North and South Korea, China, Pakistan, and Kashmir. This genus has been reported to have biological capabilities; however, research has been conducted on Dryopteris juxtapostia. Therefore, with the present study, we aimed to exploring the biological potential of D. juxtapostia root and shoot extracts. We extracted dichloromethane and methanol separately from the roots and shoots of D. juxtapostia. Antioxidant activity was determined using DPPH, FRAP, and H2O2 assays, and anti-inflammatory activities were evaluated using both in vitro (antiurease activity) and in vivo (carrageenan- and formaldehyde-induced paw edema) studies. Toxicity was evaluated by adopting a brine shrimp lethality assay followed by determination of cytotoxic activity using an MTT assay. Hepatoprotective effects of active crude extracts were examined in rats. Activity-bearing compounds were tentatively identified using LC-ESI-MS/MS analysis. Results suggested that D. juxtapostia root dichloromethane extract exhibited better antioxidant (DPPH, IC50 of 42.0 µg/mL; FRAP, 46.2 mmol/g; H2O2, 71% inhibition), anti-inflammatory (urease inhibition, 56.7% at 50 µg/mL; carrageenan-induced edema inhibition, 61.7% at 200 µg/mL; formaldehyde-induced edema inhibition, 67.3% at 200 µg/mL), brine shrimp % mortality (100% at 1000 µg/mL), and cytotoxic (HeLa cancer, IC50 of 17.1 µg/mL; prostate cancer (PC3), IC50 of 45.2 µg/mL) effects than D. juxtapostia root methanol extract. D. juxtapostia shoot dichloromethane and methanol extracts exhibited non-influential activity in all biological assays and were not selected for hepatoprotective study. D. juxtapostia root methanol extract showed improvement in hepatic cell structure and low cellular infiltration but, in contrast the dichloromethane extract, did not show any significant improvement in hepatocyte morphology, cellular infiltration, or necrosis of hepatocytes in comparison to the positive control, i.e., paracetamol. LC-ESI-MS/MS analysis showed the presence of albaspidin PP, 3-methylbutyryl-phloroglucinol, flavaspidic acid AB and BB, filixic acid ABA and ABB, tris-desaspidin BBB, tris-paraaspidin BBB, tetra-flavaspidic BBBB, tetra-albaspidin BBBB, and kaempferol-3-O-glucoside in the dichloromethane extract, whereas kaempferol, catechin, epicatechin, quinic acid, liquitrigenin, and quercetin 7-O-galactoside in were detected in the methanol extract, along with all the compounds detected in the dichloromethane extract. Hence, D. juxtapostia is safe, alongside other species of this genus, although detailed safety assessment of each isolated compound is obligatory during drug discovery. Full article
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30 pages, 9345 KiB  
Article
Ethnopharmacological Effects of Urtica dioica, Matricaria chamomilla, and Murraya koenigii on Rotenone-Exposed D. melanogaster: An Attenuation of Cellular, Biochemical, and Organismal Markers
by Shabnam Shabir, Sumaira Yousuf, Sandeep Kumar Singh, Emanuel Vamanu and Mahendra P. Singh
Antioxidants 2022, 11(8), 1623; https://doi.org/10.3390/antiox11081623 - 21 Aug 2022
Cited by 14 | Viewed by 3239
Abstract
Natural antioxidants derived from plants have been proven to have significant inhibitory effects on the free radicals of living organisms during actively metabolization. Excessive production of free radicals increases the risk of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and motor sclerosis. [...] Read more.
Natural antioxidants derived from plants have been proven to have significant inhibitory effects on the free radicals of living organisms during actively metabolization. Excessive production of free radicals increases the risk of neurodegenerative diseases, such as Alzheimer’s disease, Parkinson’s disease, and motor sclerosis. This study aimed to compare the ethnopharmacological effects of Urtica dioica (UD), Matricaria chamomilla (MC), and Murraya koenigii (MK) on the amelioration of rotenone-induced toxicity in wild-type Drosophila melanogaster (Oregon R+) at biochemical, cellular, and behavioral levels. Phytoextracts were prepared from all three plants, i.e., UD, MC, and MK (aqueous and ethanolic fractions), and their bioactive compounds were evaluated using in vitro biochemical parameters (DPPH, ABTS, TPC, and TFC), UV-Vis, followed by FT-IR and HPLC. Third instar larvae and freshly eclosed flies were treated with 500 µM rotenone alone or in combination with UD, MC, and MK for 24 to 120 h. Following exposure, cytotoxicity (dye exclusion test), biochemical (protein estimation and acetylcholinesterase inhibition assays), and behavioral assays (climbing and jumping assays) were performed. Among all three plant extracts, MK exhibited the highest antioxidant properties due to the highest TPC, TFC, DPPH, and ABTS, followed by UD, then MC. The overall trend was MK > UD > MC. In this context, ethnopharmacological properties mimic the same effect in Drosophila, exhibiting significantly (p < 0.05) reduced cytotoxicity (trypan blue), improved biochemical parameters (proteotoxicity and AChE activity), and better behavioral parameters in the organisms cotreated with phyto extracts compared with rotenone. Conclusively, UV-Vis, FTIR, and HPLC analyses differentiated the plant extracts. The findings of this research may be beneficial in the use of select herbs as viable sources of phyto-ingredients that could be of interest in nutraceutical development and various clinical applications. Full article
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27 pages, 4859 KiB  
Article
Polyphenols from Thinned Young Apples: HPLC-HRMS Profile and Evaluation of Their Anti-Oxidant and Anti-Inflammatory Activities by Proteomic Studies
by Giulio Ferrario, Giovanna Baron, Francesca Gado, Larissa Della Vedova, Ezio Bombardelli, Marina Carini, Alfonsina D’Amato, Giancarlo Aldini and Alessandra Altomare
Antioxidants 2022, 11(8), 1577; https://doi.org/10.3390/antiox11081577 - 15 Aug 2022
Cited by 10 | Viewed by 2293
Abstract
The qualitative profile of thinned apple polyphenols (TAP) fraction (≈24% of polyphenols) obtained by purification through absorbent resin was fully investigated by LC-HRMS in positive and negative ion mode and using ESI source. A total of 68 polyphenols were identified belonging to six [...] Read more.
The qualitative profile of thinned apple polyphenols (TAP) fraction (≈24% of polyphenols) obtained by purification through absorbent resin was fully investigated by LC-HRMS in positive and negative ion mode and using ESI source. A total of 68 polyphenols were identified belonging to six different classes: flavanols, flavonols, dihydrochalchones, flavanones, flavones and organic and phenolic acids. The antioxidant and anti-inflammatory activities were then investigated in cell models with gene reporter for NRF2 and NF-κB and by quantitative proteomic (label-free and SILAC) approaches. TAP dose-dependently activated NRF2 and in the same concentration range (10–250 µg/mL) inhibited NF-κB nuclear translocation induced by TNF-α and IL-1α as pro-inflammatory promoters. Proteomic studies elucidated the molecular pathways evoked by TAP treatment: activation of the NRF2 signaling pathway, which in turn up-regulates protective oxidoreductases and their nucleophilic substrates such as GSH and NADPH, the latter resulting from the up-regulation of the pentose phosphate pathway. The increase in the enzymatic antioxidant cellular activity together with the up-regulation of the heme-oxygenase would explain the anti-inflammatory effect of TAP. The results suggest that thinned apples can be considered as a valuable source of apple polyphenols to be used in health care products to prevent/treat oxidative and inflammatory chronic conditions. Full article
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17 pages, 1980 KiB  
Article
Evaluation of Proanthocyanidins from Kiwi Leaves (Actinidia chinensis) against Caco-2 Cells Oxidative Stress through Nrf2-ARE Signaling Pathway
by Ji-Min Lv, Mostafa Gouda, Xing-Qian Ye, Zhi-Peng Shao and Jian-Chu Chen
Antioxidants 2022, 11(7), 1367; https://doi.org/10.3390/antiox11071367 - 14 Jul 2022
Cited by 7 | Viewed by 2267
Abstract
Proanthocyanidins (PAs) are considered to be effective natural byproduct and bioactive antioxidants. However, few studies have focused on their mode of action pathways. In this study, reactive oxygen species (ROS), oxidative stress indices, real-time PCR, Western blotting, confocal microscopy, and molecular docking were [...] Read more.
Proanthocyanidins (PAs) are considered to be effective natural byproduct and bioactive antioxidants. However, few studies have focused on their mode of action pathways. In this study, reactive oxygen species (ROS), oxidative stress indices, real-time PCR, Western blotting, confocal microscopy, and molecular docking were used to investigate the protective effect of purified kiwi leaves PAs (PKLPs) on Caco-2 cells’ oxidative stress mechanisms. The results confirmed that pre-treatment with PKLPs significantly reduced H2O2-induced oxidative damage, accompanied by declining ROS levels and malondialdehyde (MDA) accumulation in the Caco-2 cells. The PKLPs upregulated the expression of antioxidative enzymes (GSH-px, CAT, T-SOD) and the relative mRNA (Nrf, HO-1, SOD-1, CAT) of the nuclear factor erythroid 2-related factor (Nrf2) signaling pathway. The protein-expressing level of the Nrf2 and its relative protein (NQO-1, HO-1, SOD-1) were significantly increased (p < 0.05) in the PKLPs pre-treatment group compared to the model group. In conclusion, the novelty of this study is that it explains how PKLPs’ efficacy on the Nrf2-ARE signaling pathway, in protecting vital cells from oxidative stress, could be used for cleaner production. Full article
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Review

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27 pages, 2543 KiB  
Review
Pressurized Liquid Extraction for the Recovery of Bioactive Compounds from Seaweeds for Food Industry Application: A Review
by Ana Perez-Vazquez, Maria Carpena, Paula Barciela, Lucia Cassani, Jesus Simal-Gandara and Miguel A. Prieto
Antioxidants 2023, 12(3), 612; https://doi.org/10.3390/antiox12030612 - 01 Mar 2023
Cited by 13 | Viewed by 4186
Abstract
Seaweeds are an underutilized food in the Western world, but they are widely consumed in Asia, with China being the world’s larger producer. Seaweeds have gained attention in the food industry in recent years because of their composition, which includes polysaccharides, lipids, proteins, [...] Read more.
Seaweeds are an underutilized food in the Western world, but they are widely consumed in Asia, with China being the world’s larger producer. Seaweeds have gained attention in the food industry in recent years because of their composition, which includes polysaccharides, lipids, proteins, dietary fiber, and various bioactive compounds such as vitamins, essential minerals, phenolic compounds, and pigments. Extraction techniques, ranging from more traditional techniques such as maceration to novel technologies, are required to obtain these components. Pressurized liquid extraction (PLE) is a green technique that uses high temperatures and pressure applied in conjunction with a solvent to extract components from a solid matrix. To improve the efficiency of this technique, different parameters such as the solvent, temperature, pressure, extraction time and number of cycles should be carefully optimized. It is important to note that PLE conditions allow for the extraction of target analytes in a short-time period while using less solvent and maintaining a high yield. Moreover, the combination of PLE with other techniques has been already applied to extract compounds from different matrices, including seaweeds. In this way, the combination of PLE-SFE-CO2 seems to be the best option considering both the higher yields obtained and the economic feasibility of a scaling-up approximation. In addition, the food industry is interested in incorporating the compounds extracted from edible seaweeds into food packaging (including edible coating, bioplastics and bio-nanocomposites incorporated into bioplastics), food products and animal feed to improve their nutritional profile and technological properties. This review attempts to compile and analyze the current data available regarding the application of PLE in seaweeds to determine the use of this extraction technique as a method to obtain active compounds of interest for food industry application. Full article
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4 pages, 645 KiB  
Reply
Reply to Frański, R.; Beszterda-Buszczak, M. Comment on “Villalva et al. Antioxidant, Anti-Inflammatory, and Antibacterial Properties of an Achillea millefolium L. Extract and Its Fractions Obtained by Supercritical Anti-Solvent Fractionation against Helicobacter pylori. Antioxidants 2022, 11, 1849”
by Marisol Villalva, Jose Manuel Silvan, Teresa Alarcón-Cavero, David Villanueva-Bermejo, Laura Jaime, Susana Santoyo and Adolfo J. Martinez-Rodriguez
Antioxidants 2023, 12(7), 1384; https://doi.org/10.3390/antiox12071384 - 04 Jul 2023
Cited by 1 | Viewed by 813
Abstract
Franski and Beszterda-Buszczak [...] Full article
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6 pages, 537 KiB  
Comment
Comment on Villalva et al. Antioxidant, Anti-Inflammatory, and Antibacterial Properties of an Achillea millefolium L. Extract and Its Fractions Obtained by Supercritical Anti-Solvent Fractionation against Helicobacter pylori. Antioxidants 2022, 11, 1849
by Rafał Frański and Monika Beszterda-Buszczak
Antioxidants 2023, 12(6), 1226; https://doi.org/10.3390/antiox12061226 - 07 Jun 2023
Cited by 4 | Viewed by 1364
Abstract
Villalva et al. evaluated the potential utility of an Achillea millefolium (yarrow) extract in the control of H. pylori infection. The agar-well diffusions bioassay was applied to determine the antimicrobial activity of yarrow extracts. The supercritical anti-solvent fractionation process of yarrow extract was [...] Read more.
Villalva et al. evaluated the potential utility of an Achillea millefolium (yarrow) extract in the control of H. pylori infection. The agar-well diffusions bioassay was applied to determine the antimicrobial activity of yarrow extracts. The supercritical anti-solvent fractionation process of yarrow extract was made to give two different fractions with polar phenolic compounds and monoterpenes and sesquiterpenes, respectively. Phenolic compounds were identified by HPLC-ESIMS by using the accurate masses of [M−H] ions and the characteristic product ions. However, some of the reported product ions seem to be disputable, as described below. Full article
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