Natural Bioactive Compounds as a Promising Approach to Mitigating Oxidative Stress

Topic Information

Dear Colleagues,

Oxidative stress is a pathological condition that arises due to an imbalance between oxidants and antioxidant defense systems in the body. It is implicated in the pathogenesis of several chronic diseases, including diabetes, cancer, and neurodegenerative disorders.

Natural bioactive compounds, such as polyphenols, flavonoids, and terpenoids, offer a promising approach to mitigating oxidative stress. These compounds are found in various sources, including fruits, vegetables, and medicinal plants, and have demonstrated potent antioxidant properties capable of preventing oxidative damage to cells. Additionally, they exhibit beneficial effects, including anti-inflammatory, antibacterial, anticancer, and immune-modulating properties.

Despite their robust pharmacodynamic effects, these compounds often exhibit poor pharmacokinetics. In response, nanotechnological approaches have been leveraged to enhance the characteristics of these compounds, addressing issues such as solubility, bioavailability, and stability. This improvement aims to enhance the therapeutic efficacy of natural bioactive compounds, making them more suitable for pharmaceutical applications.

Within this topic, we welcome contributions related to natural bioactive compounds and the exploitation of their antioxidant effects in fighting oxidative stress. We encourage the exploration of green extraction methods for natural sources, the structural characterization of complex biomolecules, and investigations into their interactions with cellular receptors and enzymes. Additionally, contributions discussing the potential application of novel nanotechnologies to enhance the physicochemical characteristics of these compounds are also appreciated. 

Prof. Dr. Andrea Ragusa
Prof. Dr. Filomena Corbo
Topic Editors

Keywords

Participating Journals

Journal Name	Impact Factor	CiteScore	Launched Year	First Decision (median)	APC
Antioxidants antioxidants	6.0	10.6	2012	16.9 Days	CHF 2900	Submit
Chemistry chemistry	2.4	3.2	2019	17.2 Days	CHF 1800	Submit
International Journal of Molecular Sciences ijms	4.9	8.1	2000	16.8 Days	CHF 2900	Submit
Molecules molecules	4.2	7.4	1996	15.1 Days	CHF 2700	Submit
Pharmaceutics pharmaceutics	4.9	7.9	2009	15.5 Days	CHF 2900	Submit

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Published Papers (10 papers)

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All Antioxidants Chemistry IJMS Molecules Pharmaceutics

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15 pages, 3675 KiB  

Open AccessArticle

Exploring the Effects of Sweet Potato Leaves on Skin Health—From Antimicrobial to Immunomodulator

by Manuela Machado, Sara Silva, Manuela Pintado and Eduardo M. Costa

Molecules 2025, 30(4), 855; https://doi.org/10.3390/molecules30040855 - 13 Feb 2025

Viewed by 953

Abstract

Sweet potato leaves (SPL), an agricultural byproduct, hold significant potential in dermatological applications due to their bioactive compounds. This study evaluates the phenolic profile of SPL extracts and investigates their biological activities relevant to skin health. Extract fingerprinting, through uHPLC-DAD and LC–MS, identified [...] Read more.

Sweet potato leaves (SPL), an agricultural byproduct, hold significant potential in dermatological applications due to their bioactive compounds. This study evaluates the phenolic profile of SPL extracts and investigates their biological activities relevant to skin health. Extract fingerprinting, through uHPLC-DAD and LC–MS, identified phenolic acids and flavonoids, with cynarin, neochlorogenic acid, and spiraeoside being predominant. The presence of hyperoside was detected. From a biological standpoint, SPL demonstrated notable antimicrobial activity, with MICs ranging from 2.5 to 5 mg/mL against various bacterial strains, such as MRSA and P. aeruginosa, and effective antibiofilm activity, as it reduced biofilm formation by over 80% for most tested strains. When evaluating its effect upon keratinocytes, the cytotoxicity assessment revealed safe usage concentrations at 111 µg/mL and immunomodulatory capacities, as it increased IL-6 production in unchallenged cells but had no synergistic effects under inflammatory stimuli. While preliminary, and with more assays being necessary, these findings highlight SPL’s potential as a natural agent for antimicrobial and anti-inflammatory applications in skin-related applications and open a new avenue for a possible added value application of SPL. Full article

(This article belongs to the Topic Natural Bioactive Compounds as a Promising Approach to Mitigating Oxidative Stress)

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39 pages, 6889 KiB  

Open AccessReview

Insights into the Sources, Structure, and Action Mechanisms of Quinones on Diabetes: A Review

by Tingting Zhang, Mingyue Li, Jingyang Lu, Jia Wang, Min Zhang, Pharkphoom Panichayupakaranant and Haixia Chen

Molecules 2025, 30(3), 665; https://doi.org/10.3390/molecules30030665 - 3 Feb 2025

Viewed by 1391

Abstract

Quinones, one of the oldest organic compounds, are of increasing interest due to their abundant presence in a wide range of natural sources and their remarkable biological activity. These compounds occur naturally in green leafy vegetables, fruits, herbs, animal and marine sources, and [...] Read more.

Quinones, one of the oldest organic compounds, are of increasing interest due to their abundant presence in a wide range of natural sources and their remarkable biological activity. These compounds occur naturally in green leafy vegetables, fruits, herbs, animal and marine sources, and fermented products, and have demonstrated promising potential for use in health interventions, particularly in the prevention and management of type 2 diabetes (T2DM). This review aims to investigate the potential of quinones as a health intervention for T2DM from the multidimensional perspective of their sources, types, structure–activity relationship, glucose-lowering mechanism, toxicity reduction, and bioavailability enhancement. Emerging research highlights the hypoglycemic activities of quinones, mainly driven by their redox properties, which lead to covalent binding, and their structural substituent specificity, which leads to their non-covalent binding to biocomplexes. Quinones can improve insulin resistance and regulate glucose homeostasis by modulating mitochondrial function, inflammation, lipid profile, gastrointestinal absorption, and by acting as insulin mimetics. Meanwhile, increasing attention is being given to research focused on mitigating the toxicity of quinones during administration and enhancing their bioavailability. This review offers a critical foundation for the development of quinone-based health therapies and functional foods aimed at diabetes management. Full article

(This article belongs to the Topic Natural Bioactive Compounds as a Promising Approach to Mitigating Oxidative Stress)

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13 pages, 1965 KiB  

Open AccessArticle

A Comparison of the Electronic Properties of Selected Antioxidants Vitamin C, Uric Acid, NAC and Melatonin with Guanosine Derivatives: A Theoretical Study

by Boleslaw T. Karwowski

Molecules 2024, 29(24), 5944; https://doi.org/10.3390/molecules29245944 - 17 Dec 2024

Viewed by 1012

Abstract

Each cell in the human body is continually exposed to harmful external and internal factors. During evolution, cells have developed various defence systems, divided into enzymatic and non-enzymatic types, to which low-weight molecule antioxidants belong. In this article, the ionisation potential and electron [...] Read more.

Each cell in the human body is continually exposed to harmful external and internal factors. During evolution, cells have developed various defence systems, divided into enzymatic and non-enzymatic types, to which low-weight molecule antioxidants belong. In this article, the ionisation potential and electron affinity, as well as global reactivity descriptors of Vitamin C, Melatonin, Uric Acids, and N-acetyl-L-cysteine, were theoretically investigated at the MP-2/aug-cc-pVTZ level of theory in the condensed (aqueous) phase. The vertical ionisation potential and electron affinity are discussed in terms of non-equilibrated and equilibrated solvent–solute interactions. Additionally, at the same theoretical level, the electronic properties of canonical and oxidised derivatives of guanine were analysed. The presented results indicate that the selected antioxidants for this study (Vitamin C, Uric Acid, NAC, and Melatonin) exhibit the highest adiabatic electron affinity, while guanine derivatives (Gua, ^OXOGua, Guo, dGuo, ^OXOGuo, ^OXOdGuo) are more prone to adiabatic radical cation formation. A red-ox balance (redox homeostasis) is crucial for intracellular signalling pathways that are reactive oxygen and nitrogen species (RO/NS)-dependent. Should this gentle balance be disrupted, either by an overload or deficit of species, physiological consequences may result, which in turn lead to pathological outcomes. On the other hand, maintaining the stability of the above balance of antioxidants/radicals may result in the improved effectiveness and safety of anticancer radiotherapy/chemotherapy or combined therapies with a subsequent increase in a patient’s quality of life. Full article

(This article belongs to the Topic Natural Bioactive Compounds as a Promising Approach to Mitigating Oxidative Stress)

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24 pages, 3827 KiB  

Open AccessArticle

Berries, Leaves, and Flowers of Six Hawthorn Species (Crataegus L.) as a Source of Compounds with Nutraceutical Potential

by Natalia Żurek, Michał Świeca and Ireneusz Tomasz Kapusta

Molecules 2024, 29(23), 5786; https://doi.org/10.3390/molecules29235786 - 7 Dec 2024

Viewed by 1088

Abstract

Designing new forms of food, food additives, and nutraceuticals is necessary due to the growing needs of consumers, as well as the inflammation of civilization diseases, the prevention and treatment of which can be significantly supported by dietary intervention. For this reason, this [...] Read more.

Designing new forms of food, food additives, and nutraceuticals is necessary due to the growing needs of consumers, as well as the inflammation of civilization diseases, the prevention and treatment of which can be significantly supported by dietary intervention. For this reason, this study aimed to obtain highly bioactive preparations in the form of powders from the fruits, leaves, and flowers of six species of hawthorn (Crataegus L.) using solid phase extraction (SPE). Ultra-performance liquid chromatography analysis (UPLC-PDA-MS/MS) showed a high concentration of phenolic compounds (in the range from 31.50 to 66.06 mg/g), including the highest concentration in hawthorn fruit preparations. Fruit preparations also showed the highest antioxidant activity (through scavenging of O₂˙⁻ and OH˙ radicals), antidiabetic activity (inhibition of α-amylase and α-glucosidase), and anticancer activity, mainly against colon cancer cells (Caco-2). At the same time, hawthorn flower preparations showed the highest biocompatibility against normal colon cells (CCD841CoN) and anti-inflammatory activity (trypsin inhibition). Correlation and principal component analysis (PCA) showed that the health-promoting potential was most influenced by the content of falavan-3-ols. The above findings provide a basis for the industrial use of the developed preparations, which is in line with the current trend in food technology related to the search for new sources of bioactive compounds and the design of highly bioactive food. Full article

(This article belongs to the Topic Natural Bioactive Compounds as a Promising Approach to Mitigating Oxidative Stress)

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20 pages, 1927 KiB  

Open AccessReview

Antioxidant Function and Application of Plant-Derived Peptides

by Zhengqing Zhu, Ziwu Xu, Yuhang Li, Yutong Fan, Yingqian Zhou, Kaixin Song and Lei Meng

Antioxidants 2024, 13(10), 1203; https://doi.org/10.3390/antiox13101203 - 6 Oct 2024

Cited by 8 | Viewed by 2691

Abstract

With the development of society and the improvement of people’s health consciousness, the demand for antioxidants is increasing. As a natural antioxidant with no toxic side effects, antioxidant peptides are widely used in food, cosmetics, medicine, and other fields because of their strong [...] Read more.

With the development of society and the improvement of people’s health consciousness, the demand for antioxidants is increasing. As a natural antioxidant with no toxic side effects, antioxidant peptides are widely used in food, cosmetics, medicine, and other fields because of their strong antioxidant capacity and easy absorption by the human body. Plant-derived antioxidant peptides have attracted more attention than animal-derived antioxidant peptides because plants are more diverse than animals and produce a large number of protein-rich by-products during the processing of their products, which are the main source of antioxidant peptides. In this review, we summarize the source, structure and activity, other biological functions, mechanism of action, and comprehensive applications of plant antioxidant peptides, and look forward to their future development trends, which will provide a reference for further research and development of plant antioxidant peptides. Full article

(This article belongs to the Topic Natural Bioactive Compounds as a Promising Approach to Mitigating Oxidative Stress)

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12 pages, 2847 KiB  

Open AccessArticle

Computational Insights into the Radical Scavenging Activity and Xanthine Oxidase Inhibition of the Five Anthocyanins Derived from Grape Skin

by Xiao-Qin Lu, Jindong Li, Bin Wang and Shu Qin

Antioxidants 2024, 13(9), 1117; https://doi.org/10.3390/antiox13091117 - 15 Sep 2024

Cited by 2 | Viewed by 1246

Abstract

Anthocyanins, typical polyphenol compounds in grape skin, have attracted increasing interest due to their health-promoting properties. In this body of work, five representative anthocyanins (Cy-3-O-glc, Dp-3-O-glc, Pn-3-O-glc, Mv-3-O-glc, and Pt-3-O-glc) were studied using [...] Read more.

Anthocyanins, typical polyphenol compounds in grape skin, have attracted increasing interest due to their health-promoting properties. In this body of work, five representative anthocyanins (Cy-3-O-glc, Dp-3-O-glc, Pn-3-O-glc, Mv-3-O-glc, and Pt-3-O-glc) were studied using the density functional theory (DFT) to elucidate structure–radical scavenging activity in the relationship and the reaction path underlying the radical-trapping process. Based on thermodynamic parameters involved in HAT, SET-PT, and SPLET mechanisms, along with the structural attributes, it was found that the C4′ hydroxyl group mainly contributes to the radical scavenging activities of the investigated compounds. Pt-3-O-glc exhibits a good antioxidant capacity among the five compounds. The preferred radical scavenging mechanisms vary in different phases. For the Pt-3-O-glc compound, the calculations indicate the thermodynamically favoured product is benzodioxole, rather than o-quinone, displaying considerably reduced energy in double HAT mechanisms. Additionally, the thermodynamic and kinetic calculations indicate that the reaction of ^•OH into the 4′-OH site of Pt-3-O-glc has a lower energy barrier (7.6 kcal/mol), a higher rate constant (5.72 × 10⁹ M⁻¹ s⁻¹), and exhibits potent ^•OH radical scavenging properties. Molecular docking results have shown the strong affinity of the studied anthocyanins with the pro-oxidant enzyme xanthine oxidase, displaying their significant role in inhibiting ROS formation. Full article

(This article belongs to the Topic Natural Bioactive Compounds as a Promising Approach to Mitigating Oxidative Stress)

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31 pages, 2531 KiB  

Open AccessReview

Treatment of Acute and Long-COVID, Diabetes, Myocardial Infarction, and Alzheimer’s Disease: The Potential Role of a Novel Nano-Compound—The Transdermal Glutathione–Cyclodextrin Complex

by Ray Yutani, Vishwanath Venketaraman and Nisar Sheren

Antioxidants 2024, 13(9), 1106; https://doi.org/10.3390/antiox13091106 - 12 Sep 2024

Viewed by 2132

Abstract

Oxidative stress (OS) occurs from excessive reactive oxygen species or a deficiency of antioxidants—primarily endogenous glutathione (GSH). There are many illnesses, from acute and post-COVID-19, diabetes, myocardial infarction to Alzheimer’s disease, that are associated with OS. These dissimilar illnesses are, in order, viral [...] Read more.

Oxidative stress (OS) occurs from excessive reactive oxygen species or a deficiency of antioxidants—primarily endogenous glutathione (GSH). There are many illnesses, from acute and post-COVID-19, diabetes, myocardial infarction to Alzheimer’s disease, that are associated with OS. These dissimilar illnesses are, in order, viral infections, metabolic disorders, ischemic events, and neurodegenerative disorders. Evidence is presented that in many illnesses, (1) OS is an early initiator and significant promotor of their progressive pathophysiologic processes, (2) early reduction of OS may prevent later serious and irreversible complications, (3) GSH deficiency is associated with OS, (4) GSH can likely reduce OS and restore adaptive physiology, (5) effective administration of GSH can be accomplished with a novel nano-product, the GSH/cyclodextrin (GC) complex. OS is an overlooked pathological process of many illnesses. Significantly, with the GSH/cyclodextrin (GC) complex, therapeutic administration of GSH is now available to reduce OS. Finally, rigorous prospective studies are needed to confirm the efficacy of this therapeutic approach. Full article

(This article belongs to the Topic Natural Bioactive Compounds as a Promising Approach to Mitigating Oxidative Stress)

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25 pages, 442 KiB  

Open AccessReview

Current Treatments, Emerging Therapeutics, and Natural Remedies for Inflammatory Bowel Disease

by Karma Yeshi, Tenzin Jamtsho and Phurpa Wangchuk

Molecules 2024, 29(16), 3954; https://doi.org/10.3390/molecules29163954 - 21 Aug 2024

Cited by 6 | Viewed by 2964

Abstract

Inflammatory bowel disease (IBD) is a chronic, lifelong disorder characterized by inflammation of the gastrointestinal (GI) tract. The exact etiology of IBD remains incompletely understood due to its multifaceted nature, which includes genetic predisposition, environmental factors, and host immune response dysfunction. Currently, there [...] Read more.

Inflammatory bowel disease (IBD) is a chronic, lifelong disorder characterized by inflammation of the gastrointestinal (GI) tract. The exact etiology of IBD remains incompletely understood due to its multifaceted nature, which includes genetic predisposition, environmental factors, and host immune response dysfunction. Currently, there is no cure for IBD. This review discusses the available treatment options and the challenges they present. Importantly, we examine emerging therapeutics, such as biologics and immunomodulators, that offer targeted treatment strategies for IBD. While many IBD patients do not respond adequately to most biologics, recent clinical trials combining biologics with small-molecule drugs (SMDs) have provided new insights into improving the IBD treatment landscape. Furthermore, numerous novel and specific therapeutic targets have been identified. The high cost of IBD drugs poses a significant barrier to treatment, but this challenge may be alleviated with the development of more affordable biosimilars. Additionally, emerging point-of-care protein biomarkers from serum and plasma are showing potential for enhancing the precision of IBD diagnosis and prognosis. Several natural products (NPs), including crude extracts, small molecules, and peptides, have demonstrated promising anti-inflammatory activity in high-throughput screening (HTS) systems and advanced artificial intelligence (AI)-assisted platforms, such as molecular docking and ADMET prediction. These platforms are advancing the search for alternative IBD therapies derived from natural sources, potentially leading to more affordable and safer treatment options with fewer side effects. Full article

(This article belongs to the Topic Natural Bioactive Compounds as a Promising Approach to Mitigating Oxidative Stress)

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18 pages, 9614 KiB  

Open AccessArticle

Functional Mechanisms of Dietary Crocin Protection in Cardiovascular Models under Oxidative Stress

by Sepideh Zununi Vahed, Marisol Zuluaga Tamayo, Violeta Rodriguez-Ruiz, Olivier Thibaudeau, Sobhan Aboulhassanzadeh, Jalal Abdolalizadeh, Anne Meddahi-Pellé, Virginie Gueguen, Abolfazl Barzegari and Graciela Pavon-Djavid

Pharmaceutics 2024, 16(7), 840; https://doi.org/10.3390/pharmaceutics16070840 - 21 Jun 2024

Cited by 3 | Viewed by 1684

Abstract

It was previously reported that crocin, a water-soluble carotenoid isolated from the Crocus sativus L. (saffron), has protective effects on cardiac cells and may neutralize and even prevent the formation of excess number of free radicals; however, functional mechanisms of crocin activity have [...] Read more.

It was previously reported that crocin, a water-soluble carotenoid isolated from the Crocus sativus L. (saffron), has protective effects on cardiac cells and may neutralize and even prevent the formation of excess number of free radicals; however, functional mechanisms of crocin activity have been poorly understood. In the present research, we aimed to study the functional mechanism of crocin in the heart exposed to oxidative stress. Accordingly, oxidative stress was modeled in vitro on human umbilical vein endothelial cells (HUVECs) and in vivo in mice using cellular stressors. The beneficial effects of crocin were investigated at cellular and molecular levels in HUVECs and mice hearts. Results indicated that oral administration of crocin could have protective effects on HUVECs. In addition, it protects cardiac cells and significantly inhibits inflammation via modulating molecular signaling pathways TLR4/PTEN/AKT/mTOR/NF-κB and microRNA (miR-21). Here we show that crocin not only acts as a direct free radical scavenger but also modifies the gene expression profiles of HUVECs and protects mice hearts with anti-inflammatory action under oxidative stress. Full article

(This article belongs to the Topic Natural Bioactive Compounds as a Promising Approach to Mitigating Oxidative Stress)

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18 pages, 9765 KiB  

Open AccessArticle

Stress Granule Core Protein-Derived Peptides Inhibit Assembly of Stress Granules and Improve Sorafenib Sensitivity in Cancer Cells

by Juan Li, Yaobin Zhang, Jinxuan Gu, Yulin Zhou, Jie Liu, Haiyan Cui, Tiejun Zhao and Zhigang Jin

Molecules 2024, 29(9), 2134; https://doi.org/10.3390/molecules29092134 - 4 May 2024

Cited by 1 | Viewed by 2755

Abstract

Upon a variety of environmental stresses, eukaryotic cells usually recruit translational stalled mRNAs and RNA-binding proteins to form cytoplasmic condensates known as stress granules (SGs), which minimize stress-induced damage and promote stress adaptation and cell survival. SGs are hijacked by cancer cells to [...] Read more.

Upon a variety of environmental stresses, eukaryotic cells usually recruit translational stalled mRNAs and RNA-binding proteins to form cytoplasmic condensates known as stress granules (SGs), which minimize stress-induced damage and promote stress adaptation and cell survival. SGs are hijacked by cancer cells to promote cell survival and are consequently involved in the development of anticancer drug resistance. However, the design and application of chemical compounds targeting SGs to improve anticancer drug efficacy have rarely been studied. Here, we developed two types of SG inhibitory peptides (SIPs) derived from SG core proteins Caprin1 and USP10 and fused with cell-penetrating peptides to generate TAT-SIP-C1/2 and SIP-U1-Antp, respectively. We obtained 11 SG-inducing anticancer compounds from cell-based screens and explored the potential application of SIPs in overcoming resistance to the SG-inducing anticancer drug sorafenib. We found that SIPs increased the sensitivity of HeLa cells to sorafenib via the disruption of SGs. Therefore, anticancer drugs which are competent to induce SGs could be combined with SIPs to sensitize cancer cells, which might provide a novel therapeutic strategy to alleviate anticancer drug resistance. Full article

(This article belongs to the Topic Natural Bioactive Compounds as a Promising Approach to Mitigating Oxidative Stress)

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