Natural Antioxidant Molecules Research Articles

Nano-Formulations of Natural Antioxidants for the Treatment of Liver Cancer.

Oxidative stress is a key factor in the pathological processes that trigger various chronic liver diseases, and significantly contributes to the development of hepatocarcinogenesis. Natural antioxidants reduce oxidative stress by neutralizing free radicals and play a crucial role in the treatment of free-radical-induced liver diseases. However, their efficacy is often limited by poor bioavailability and metabolic stability. To address these limitations, recent advances have focused on developing nano-drug delivery systems that protect them from degradation and enhance their therapeutic potential. Among the several critical benefits, they showed to be able to improve bioavailability and targeted delivery, thereby reducing off-target effects by specifically directing the antioxidant to the liver tumor site. Moreover, these nanosystems led to sustained release, prolonging the therapeutic effect over time. Some of them also exhibited synergistic effects when combined with other therapeutic agents, allowing for improved overall efficacy. This review aims to discuss recent scientific advances in nano-formulations containing natural antioxidant molecules, highlighting their potential as promising therapeutic approaches for the treatment of liver cancer. The novelty of this review lies in its comprehensive focus on the latest developments in nano-formulations of natural antioxidants for the treatment of liver cancer.

Dual Functional Antibacterial-Antioxidant Core/Shell Alginate/Poly(ε-caprolactone) Nanofiber Membrane: A Potential Wound Dressing.

Core/shell nanofibers offer the advantage of encapsulating multiple drugs with different hydrophilicity in the core and shell, thus allowing for the controlled release of pharmaceutic agents. Specifically, the burst release of hydrophilic drugs from such fiber membranes causes an instantaneous high drug concentration, whereas a long and steady release is usually desired. Herein, we tackle the problem of the initial burst release by the generation of core/shell nanofibers with the hydrophilic antibiotic drug gentamycin loaded within a hydrophilic alginate core surrounded by a hydrophobic shell of poly(ε-caprolactone). Emulsion electrospinning was used as the nanofibrous mesh generation procedure. This process also allows for the loading of a hydrophobic compound, where we selected a natural antioxidant molecule, betulin (BTL), to detoxify the radicals. The resulting nanofibers exhibited a cylindrical shape with a core/shell structure. In vitro tests showed a controlled release of gentamicin from nanofibers via diffusion. The drug reached 93% release in an alginate hydrogel film but only 50% release in the nanofibers, suggesting its potential to minimize the initial burst release. Antibacterial tests revealed significant activity against both Gram-negative and Gram-positive bacteria. The antioxidant property of betulin was confirmed through the DPPH assay, where the incorporation of 20% BTL revealed 37.3% DPPH scavenging. The nanofibers also exhibited favorable biocompatibility in cell culture studies, and no harmful effects on cell viability were observed. Overall, this research offers a promising approach to producing core/shell nanofibrous mats with antibacterial and antioxidant properties, which could effectively address the requirements of wound dressings, including infection prevention and wound healing acceleration.

In Vitro Evaluation of the Antioxidant Capacity of 3,3-Disubstituted-3H-benzofuran-2-one Derivatives in a Cellular Model of Neurodegeneration.

Oxidative stress represents a hallmark for many degenerative pathologies of the Central Nervous System. Throughout life, the constant pressure of noxious stimuli and/or episodes of traumatic events may expose the brain to a microenvironment where the non-balanced reactive oxygen species inevitably lead to neuronal loss and cognitive decline. HO-1, a 32 kDa heat-shock protein catalyzing the degradation of heme into carbon monoxide (CO), iron and biliverdin/bilirubin is considered one of the main antioxidant defense mechanisms playing pivotal roles in neuroprotection. Restoring the redox homeostasis is the goal of many natural or synthetic antioxidant molecules pursuing beneficial effects on brain functions. Here, we investigated the antioxidant capacity of four selected benzofuran-2-one derivatives in a cellular model of neurodegeneration represented by differentiated SH-SY5Y cells exposed to catechol-induced oxidative stress. Our main results highlight how all the molecules have antioxidant properties, especially compound 9, showing great abilities in reducing intracellular ROS levels and protecting differentiated SH-SY5Y cells from catechol-induced death. This compound above all seems to boost HO-1 mRNA and perinuclear HO-1 protein isoform expression when cells are exposed to the oxidative insult. Our findings open the way to consider benzofuran-2-ones as a novel and promising adjuvant antioxidant strategy for many neurodegenerative disorders.

Luteoloside inhibits Aβ1–42 fibrillogenesis, disintegrates preformed fibrils, and alleviates amyloid-induced cytotoxicity

Abnormal aggregation and fibrillogenesis of amyloid-β protein (Aβ) can cause Alzheimerʼs disease (AD). Thus, the discovery of effective drugs that inhibit Aβ fibrillogenesis in the brain is crucial for the treatment of AD. Luteoloside, as one of the polyphenolic compounds, is found to have a certain therapeutic effect on nervous system diseases. However, it remains unknown whether luteoloside is a potential drug for treating AD by modulating Aβ aggregation pathway. In this study, we performed diverse biophysical and biochemical methods to explore the inhibition of luteoloside on Aβ1–42 which is linked to AD. The results demonstrated that luteoloside efficiently prevented amyloid oligomerization and cross-β-sheet formation, reduced the rate of amyloid growth and the length of amyloid fibrils in a dose-dependent manner. Moreover, luteoloside was able to influence aggregation and conformation of Aβ1–42 during different fiber-forming phases, and it could disintegrate already preformed fibrils of Aβ1–42 and convert them into nontoxic aggregates. Furthermore, luteoloside protected cells from amyloid-induced cytotoxicity and hemolysis, and attenuated the level of reactive oxygen species (ROS). The molecular docking study showed that luteoloside interacted with Aβ1–42 mainly via Conventional Hydrogen Bond, Carbon Hydrogen Bond, Pi-Pi T-shaped, Pi-Alkyl and Pi-Anion, thereby possibly preventing it from forming the aggregates. These observations indicate that luteoloside, a natural anti-oxidant molecule, may be applicable as an effective inhibitor of Aβ, and promote further exploration of the therapeutic strategy against AD.

MEK-inhibitors decrease Nfix in muscular dystrophy but induce unexpected calcifications, partially rescued with Cyanidin diet

Muscular dystrophies (MDs) are incurable genetic myopathies characterized by progressive degeneration of skeletal muscles. Dystrophic mice lacking the transcription factor Nfix display morphological and functional improvements of the disease. Recently, we demonstrated that MAPK signaling pathway positively regulates Nfix in muscle development and that Cyanidin, a natural antioxidant molecule, strongly ameliorates the pathology. To explore a synergistic approach aimed at treating MDs, we administered Trametinib, a clinically approved MEK inhibitor, alone or combined with Cyanidin to adult Sgca null mice. We observed that chronic treatment with Trametinib and Cyanidin reduced Nfix in myogenic cells but, unexpectedly, caused ectopic calcifications exclusively in dystrophic muscles. The combined treatment with Cyanidin resulted in histological improvements by preventing Trametinib-induced calcifications in Diaphragm and Soleus. Collectively, this first pilot study revealed that Nfix is modulated by the MAPK pathway in MDs, and that Cyanidin partly rescued the unexpected ectopic calcifications caused by MEK inhibition.

Preventive Anti-inflammatory Effects of Apocynin on Acetic Acid-Induced Colitis in Rats.

Ulcerative colitis is an inflammatory bowel disease with a complex aetiology characterised by abnormal immune responses and oxidative stress-induced tissue injury. Inflammatory cells play an important role in the progression of this pathology through the overproduction of reactive oxygen species (ROS) from various sources including the NADPH oxidases (NOXs). The aim of this study was to investigate the preventive effect of apocynin, a natural antioxidant molecule and a selective inhibitor of NOXs, on acetic acid (AA)-induced ulcerative colitis in rats. Our results first confirmed that apocynin has a high free radical scavenging capacity as well as a potent iron chelating ability. Oral pretreatment of rats with apocynin (200mg/kg and 400mg/kg) for 7days prior to AA-induced colitis suppressed the increase in pro-oxidant markers in colonic homogenates and preserved colonic cytoarchitecture from acetic acid-induced damage. Oral administration of apocynin (200mg/kg and 400mg/kg) also reduced several systemic inflammatory markers such as alkaline phosphatase, iron, pro-inflammatory cytokines, C-reactive protein and myeloperoxidase. This study shows that apocynin protects rats from acetic acid-induced colonic inflammation and suggests that apocynin may have a promising beneficial effect in the prevention of ulcerative colitis.

Subcritical Water Extraction of Phenolic Compounds from Vaccinium Dunalianum Wight Leaves and Their Antioxidant and Tyrosinase Inhibitory Activities in Vitro

Subcritical water extraction was used to extract bioactive phenolic compounds from Vaccinium dunalianum Wight leaves. The optimal extraction conditions were determined as an extraction temperature of 150 °C, an extraction time of 40 min, and a liquid-solid ratio of 35 : 1 mL/g. The total phenolic content reached 21.35 mg gallic acid /g, which was 16 % higher than that by hot water extraction. The subcritical water extraction extract exhibited strong scavenging activity of DPPH free radical and ABTS+ free radical, as well as significant tyrosinase inhibitory activity. The study suggests that subcritical water extraction can alter the composition of the extracts, leading to the production of various phenolic compounds, effective antioxidants, and tyrosinase inhibitors from Vaccinium dulciana Wight leaves. These findings confirm the potential of Vaccinium dunalianum Wight as a natural antioxidant molecule source for the medicine and food industries, and for the therapy of skin pigmentation disorders.

Repairing and Preventing Photooxidation of Few-Layer Black Phosphorus with β-Carotene

Few-layer black phosphorus (FLBP), a technologically important 2D material, faces a major hurdle to consumer applications: spontaneous degradation under ambient conditions. Blocking the direct exposure of FLBP to the environment has remained the key strategy to enhance its stability, but this can also limit its utility. In this paper, a more ambitious approach to handling FLBP is reported where not only is FLBP oxidation blocked, but it is also repaired postoxidation. Our approach, inspired by nature, employs the antioxidant molecule β-carotene that protects plants against photooxidative damages to act as a protecting and repairing agent for FLBP. The mechanistic role of β-carotene is established by a suite of spectro-microscopy techniques, in combination with computational studies and biochemical assays. Transconductance studies on FLBP-based field effect transistor (FET) devices further affirm the protective and reparative effects of β-carotene. The outcomes indicate the potential for deploying a plethora of natural antioxidant molecules to enhance the stability of other environmentally sensitive inorganic nanomaterials and expedite their translation for technological and consumer applications.

Niosomes for Topical Application of Antioxidant Molecules: Design and In Vitro Behavior

In the present study, gels based on xanthan gum and poloxamer 407 have been developed and characterized in order to convey natural antioxidant molecules included in niosomes. Specifically, the studies were conducted to evaluate how the vesicular systems affect the release of the active ingredient and which formulation is most suitable for cutaneous application. Niosomes, composed of Span 20 or Tween 20, were produced through the direct hydration method, and therefore, borate buffer or a micellar solution of poloxamer 188 was used as the aqueous phase. The niosomes were firstly characterized in terms of morphology, dimensional and encapsulation stability. Afterwards, gels based on poloxamer 407 or xanthan gum were compared in terms of spreadability and adhesiveness. It was found to have greater spreadability for gels based on poloxamer 407 and 100% adhesiveness for those based on xanthan gum. The in vitro diffusion of drugs studied using Franz cells associated with membranes of mixed cellulose esters showed that the use of a poloxamer micellar hydration phase determined a lower release as well as the use of Span 20. The thickened niosomes ensured controlled diffusion of the antioxidant molecules. Lastly, the in vivo irritation test confirmed the safeness of niosomal gels after cutaneous application.

Extraction Systems and Analytical Techniques for Food Phenolic Compounds: A Review.

Phenolic compounds are highly valuable food components due to their potential utilisation as natural bioactive and antioxidant molecules for the food, cosmetic, chemical, and pharmaceutical industries. For this purpose, the development and optimisation of efficient extraction methods is crucial to obtain phenolic-rich extracts and, for some applications, free of interfering compounds. It should be accompanied with robust analytical tools that enable the standardisation of phenolic-rich extracts for industrial applications. New methodologies based on both novel extraction and/or analysis are also implemented to characterise and elucidate novel chemical structures and to face safety, pharmacology, and toxicity issues related to phenolic compounds at the molecular level. Moreover, in combination with multivariate analysis, the extraction and analysis of phenolic compounds offer tools for plant chemotyping, food traceability and marker selection in omics studies. Therefore, this study reviews extraction techniques applied to recover phenolic compounds from foods and agri-food by-products, including liquid-liquid extraction, solid-liquid extraction assisted by intensification technologies, solid-phase extraction, and combined methods. It also provides an overview of the characterisation techniques, including UV-Vis, infra-red, nuclear magnetic resonance, mass spectrometry and others used in minor applications such as Raman spectroscopy and ion mobility spectrometry, coupled or not to chromatography. Overall, a wide range of methodologies are now available, which can be applied individually and combined to provide complementary results in the roadmap around the study of phenolic compounds.

Therapeutic and Nutraceutical Effects of Polyphenolics from Natural Sources.

The prevalence of cardiovascular disease, oxidative stress-related complications, and chronic age-related illnesses is gradually increasing worldwide. Several causes include the ineffectiveness of medicinal treatment therapies, their toxicity, their inability to provide radical solutions in some diseases, and the necessity of multiple drug therapy in certain chronic diseases. It is therefore necessary for alternative treatment methods to be sought. In this review, polyphenols were identified and classified according to their chemical structure, and the sources of these polyphenol molecules are indicated. The cardioprotective, ROS scavenging, anti-aging, anticancer properties of polyphenolic compounds have been demonstrated by the results of many studies, and these natural antioxidant molecules are potential alternative therapeutic agents.

Bioactive Compounds and Antioxidant Properties with Involved Mechanisms of Eugenia involucrata DC Fruits.

In this study, the phytochemical profile and the antioxidative properties of Eugenia involucrata fruits were evaluated. Spectrophotometric assays indicated that these berries are a rich source of polyphenols with very high radical-scavenging and metal-reducing activities. High-performance liquid chromatography–Orbitrap analysis was able to carry out the annotation of 36 different compounds, mainly belonging to the flavonol, flavan-3-ol, and anthocyanin families. Antioxidant activity of the fruit extract was evaluated in a cell-based lipid peroxidation model. Obtained data showed that the extract, at very low concentration, was able to prevent oxidative damage in HepG2 cells exposed to oxidative stimuli. Moreover, the evaluation of the gene expression of the most important antioxidant enzymes suggested that the observed antioxidant protection in cells also involves an improvement in enzymatic antioxidant defenses. Finally, the collected data show that E. involucrata fruits are a good source of natural antioxidant molecules and provide evidence of their potential application in the nutraceutical field.

Protective Effects of Diets Rich in Polyphenols in Cigarette Smoke (CS)-Induced Oxidative Damages and Associated Health Implications.

Cigarette smoking has been responsible for causing many life-threatening diseases such as pulmonary and cardiovascular diseases as well as lung cancer. One of the prominent health implications of cigarette smoking is the oxidative damage of cellular constituents, including proteins, lipids, and DNA. The oxidative damage is caused by reactive oxygen species (ROS, oxidants) present in the aqueous extract of cigarette smoke (CS). In recent years, there has been considerable interest in the potential health benefits of dietary polyphenols as natural antioxidant molecules. Epidemiological studies strongly suggest that long-term consumption of diets (fruits, vegetables, tea, and coffee) rich in polyphenols offer protective effects against the development of cancer, cardiovascular diseases, diabetes, osteoporosis, and neurodegenerative diseases. For instance, green tea has chemopreventive effects against CI-induced lung cancer. Tea might prevent CS-induced oxidative damages in diseases because tea polyphenols, such as catechin, EGCG, etc., have strong antioxidant properties. Moreover, apple polyphenols, including catechin and quercetin, provide protection against CS-induced acute lung injury such as chronic obstructive pulmonary disease (COPD). In CS-induced health problems, the antioxidant action is often accompanied by the anti-inflammatory effect of polyphenols. In this narrative review, the CS-induced oxidative damages and the associated health implications/pathological conditions (or diseases) and the role of diets rich in polyphenols and/or dietary polyphenolic compounds against various serious/chronic conditions of human health have been delineated.

Curcumin-loaded human endometrial stem cells derived exosomes as an effective carrier to suppress alpha-synuclein aggregates in 6OHDA-induced Parkinson's disease mouse model.

Parkinson disease (PD) is considered as one of the most worldwide neurodegenerative disorders. The major reasons associated to neurodegeneration process of PD pathogenesis are oxidative stress. Many studies reported that natural antioxidant molecules, especially, curcumin can suppress inflammatory pathways and preserve dopaminergic neurons damage in PD. Further, the poor pharmacokinetics, instability of chemical structure because of fast hydrolytic degradation at physiologic condition and especially, the presence of the blood brain barrier (BBB) has regarded as a considerable restriction factor for transfer of neurotherapeutic molecules to the brain tissue. The present research aims to the fabrication of nanoformulated curcumin loaded human endometrial stem cells derived exosomes (hEnSCs EXOs-Cur) to study on enhancing curcumin penetration to the brain across BBB and to improve anti- Parkinsonism effects of curcumin against neural death and alpha-synuclein aggregation. hEnSCs EXOs-Cur characterization results demonstrated the accurate size and morphology of formulated curcumin loaded exosomes with a proper stability and sustained release profile. In vivo studies including behavioral, Immunohistochemical and molecular evaluations displayed that novel formulation of hEnSCs EXO-Cur is able to cross BBB, enhance motor uncoordinated movements, suppress the aggregation of αS protein and rescue neuronal cell death through elevation of BCL2 expression level as an anti-apoptotic protein and the expression level reduction of BAX and Caspase 3 as apoptotic markers.

Biodegradable Active Packaging with Controlled Release: Principles, Progress, and Prospects

Climate change is accelerated by increasing food waste; more importantly, this pressing challenge is compounded by the environmentally damaging effects of conventional plastics used in food packaging. We have critically reviewed active release packaging as an innovative solution to address these concerning effects. Particular attention is paid to controlled release, encapsulation methods, and natural active agents. Other aspects of active packaging development such as stringent safety legislations are also discussed, alongside highlighting developmental hurdles. Certain technologies are underscored as revolutionary for the field of active packaging: in particular, stimuli-responsive materials, reliable controlled-release mechanisms, and the synergy of active packaging and intelligent packaging. Encapsulation is described as an important method of achieving controlled release. The potential of electrospun biopolymeric fibers to encapsulate natural antimicrobial or antioxidant molecules is also noted. Importantly, the review discusses the incorporation of nanomaterials and subsequent increased commercialization success due to the modulation of Bioplastic properties. In order to outcompete inexpensive petroleum-based plastics, these novel packaging materials must have good mechanical properties, good barrier properties, well-defined controlled release studies, and good biodegradation rates. Overall, it is evident that biopolymeric active-release packaging incorporating natural active compounds will serve as a high-potential, sustainable replacement for ubiquitous petroleum-based plastics.

Production of biologically active hydroxytyrosol rich extract via catalytic conversion of tyrosol.

An effective and economical process was established to produce hydroxytyrosol, a naturally occurring orthodiphenolic antioxidant molecule found in olive oil from its monophenolic precursor tyrosol. The approach proposed in the present work presents an environment-friendly method based on wet hydrogen peroxide catalytic oxidation with montmorillonite KSF as an inexpensive and environmentally benign solid acid at room temperature. The influence of the principal operating parameters including concentration of tyrosol, H2O2, and catalyst used were studied. The antioxidant activity was realized by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. High antioxidant activity was detected according to the high hydroxytyrosol production (IC50 = 0.7 μg mL−1). The bactericidal and fungicidal properties of hydroxytyrosol rich extract were investigated using the NCCLS broth dilution and EN 1276 standard methods. Positive bactericidal and fungicidal effects of concentrations ranging between 1–0.5 g L−1 and 4–2 g L−1 were obtained.

Oxidative Stress and Cognitive Decline: The Neuroprotective Role of Natural Antioxidants.

Free- radicals (Oxygen and Nitrogen species) are formed in mitochondria during the oxidative phosphorylation. Their high reactivity, due to not-engaged electrons, leads to an increase of the oxidative stress. This condition affects above all the brain, that usually needs a large oxygen amount and in which there is the major possibility to accumulate “Reacting Species.” Antioxidant molecules are fundamental in limiting free-radical damage, in particular in the central nervous system: the oxidative stress, in fact, seems to worsen the course of neurodegenerative diseases. The aim of this review is to sum up natural antioxidant molecules with the greatest neuroprotective properties against free radical genesis, understanding their relationship with the Central Nervous System.

Virgin coconut oil complements with its polyphenol components mitigate sodium fluoride toxicity in vitro and in vivo

Virgin coconut oil (VCO), prepared from fresh coconut kernel without any chemical refining, is an emerging functional food. The pharmacological benefits of VCO are believed to be due to the natural combination of phenolics. Although cell culture studies have demonstrated the antioxidant activity of VCO under different oxidative stress conditions, a valid in vivo demonstration of the antioxidant activity of VCO is yet to come. Sodium fluoride (NaF), an environmental pollutant, is widely used to induce oxidative stress in cell culture models and rodents to test the antioxidant potential of several compounds. Herein, VCO and its polyphenolic (VCOP) and non-phenolic oil fraction (VCOF) were individually tested in fluoride-exposed normal intestinal cells (IEC-6) and mice to address their contribution to the documented antioxidant potential. It was found that pretreatment of VCOP (40 µg/mL) was effective in mitigating the fluoride-induced cell death when compared to VCO (200 µg/mL) and VCOF (160 µg/mL). Further, exposure to fluoride (10 mM), increased the intracellular ROS measured based on the dichlorofluorescein (DCF) fluorescence, and this, in turn, was significantly reduced when the cells were supplemented with VCOP. Oral administration of VCO (2 mL/kg bwt) reversed the drop in the hepatic catalase and SOD activities to near normal with a minimal level of lipid peroxidation in fluoride intoxicated mice. However, VCOP and VCOF were less effective in lowering the fluoride-induced increase in hepatic oxidative stress markers. It is reasoned that the oil components of VCO complement the natural antioxidant molecules resulting in an overall increase in their bioavailability.

Antioxidant Properties of Ergosterol and Its Role in Yeast Resistance to Oxidation.

Although the functions and structural roles of sterols have been the subject of numerous studies, the reasons for the diversity of sterols in the different eukaryotic kingdoms remain unclear. It is thought that the specificity of sterols is linked to unidentified supplementary functions that could enable organisms to be better adapted to their environment. Ergosterol is accumulated by late branching fungi that encounter oxidative perturbations in their interfacial habitats. Here, we investigated the antioxidant properties of ergosterol using in vivo, in vitro, and in silico approaches. The results showed that ergosterol is involved in yeast resistance to tert-butyl hydroperoxide and protects lipids against oxidation in liposomes. A computational study based on quantum chemistry revealed that this protection could be related to its antioxidant properties operating through an electron transfer followed by a proton transfer mechanism. This study demonstrates the antioxidant role of ergosterol and proposes knowledge elements to explain the specific accumulation of this sterol in late branching fungi. Ergosterol, as a natural antioxidant molecule, could also play a role in the incompletely understood beneficial effects of some mushrooms on health.

A Review on Coordination Properties of Al(III) and Fe(III) toward Natural Antioxidant Molecules: Experimental and Theoretical Insights.

This review focuses on the ability of some natural antioxidant molecules (i.e., hydroxycinnamic acids, coumarin-3-carboxylic acid, quercetin, luteolin and curcumin) to form Al(III)- and Fe(III)-complexes with the aim of evaluating the coordination properties from a combined experimental and theoretical point of view. Despite the contributions of previous studies on the chemical properties and biological activity of these metal complexes involving such natural antioxidants, further detailed relationships between the structure and properties are still required. In this context, the investigation on the coordination properties of Al(III) and Fe(III) toward these natural antioxidant molecules might deserve high interest to design water soluble molecule-based metal carriers that can improve the metal’s intake and/or its removal in living organisms.