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Neuron Oct 2022For many cancer patients, chemotherapy produces untreatable life-long neurologic effects termed chemotherapy-related cognitive impairment (CRCI). We discovered that the...
For many cancer patients, chemotherapy produces untreatable life-long neurologic effects termed chemotherapy-related cognitive impairment (CRCI). We discovered that the chemotherapy methotrexate (MTX) adversely affects oxidative metabolism of non-cancerous choroid plexus (ChP) cells and the cerebrospinal fluid (CSF). We used a ChP-targeted adeno-associated viral (AAV) vector approach in mice to augment CSF levels of the secreted antioxidant SOD3. AAV-SOD3 gene therapy increased oxidative defense capacity of the CSF and prevented MTX-induced lipid peroxidation in the hippocampus. Furthermore, this gene therapy prevented anxiety and deficits in short-term learning and memory caused by MTX. MTX-induced oxidative damage to cultured human cortical neurons and analyses of CSF samples from MTX-treated lymphoma patients demonstrated that MTX diminishes antioxidant capacity of patient CSF. Collectively, our findings motivate the advancement of ChP- and CSF-targeted anti-oxidative prophylactic measures to relieve CRCI.
Topics: Humans; Animals; Mice; Antioxidants; Choroid Plexus; Methotrexate; Oxidative Stress; Hippocampus; Neoplasms
PubMed: 36070751
DOI: 10.1016/j.neuron.2022.08.009 -
Molecules (Basel, Switzerland) Aug 2021Numerous plant compounds and their metal-ion complexes exert antioxidative, anti-inflammatory, anticancer, and other beneficial effects. This review highlights the... (Review)
Review
Numerous plant compounds and their metal-ion complexes exert antioxidative, anti-inflammatory, anticancer, and other beneficial effects. This review highlights the different bioactivities of flavonoids, chromones, and coumarins and their metal-ions complexes due to different structural characteristics. In addition to insight into the most studied antioxidative properties of these compounds, the first part of the review provides a comprehensive overview of exogenous and endogenous sources of reactive oxygen and nitrogen species, oxidative stress-mediated damages of lipids and proteins, and on protective roles of antioxidant defense systems, including plant-derived antioxidants. Additionally, the review covers the anti-inflammatory and antimicrobial activities of flavonoids, chromones, coumarins and their metal-ion complexes which support its application in medicine, pharmacy, and cosmetology.
Topics: Anti-Inflammatory Agents; Antioxidants; Coordination Complexes; Free Radicals; Humans; Ions; Metals; Phytochemicals; Plants
PubMed: 34443474
DOI: 10.3390/molecules26164886 -
Triterpenes and Aromatic Meroterpenoids with Antioxidant Activity and Neuroprotective Effects from .Molecules (Basel, Switzerland) Nov 2019Reactive oxygen/nitrogen species generated in the human body can cause oxidative damage associated with many degenerative diseases such as atherosclerosis, dementia,...
Reactive oxygen/nitrogen species generated in the human body can cause oxidative damage associated with many degenerative diseases such as atherosclerosis, dementia, coronary heart diseases, aging, and cancer. There is a great interest in developing new antioxidants from fungus due to its low toxicity. As part of our ongoing search for antioxidative constituents from the fruiting bodies of , the chemical constituents were investigated and seven secondary metabolites, including one new lanostane triterpene (), two known aromatic meroterpenoids (-), and four known triterpenes (-), were isolated by a series of chromatographic methods. The structures of the seven compounds were elucidated by spectroscopic techniques. The isolated compounds were tested in vitro for antioxidant potencies and neuroprotective activities against HO and aged Aβ-induced cell death in SH-SY5Y cells. As a result, compounds , , and exhibited potent antioxidant and neuroprotective activities. Additionally, all isolated compounds were tested for radical scavenging activities. Compounds and showed the comparable free radical scavenging activities with the standard drug in both ABTS (2, 2'-azobis (3-ethylbenzothiazole-6-sulfonaic acid)) and ORAC (oxygen radical absorbance capacity) experiments. The results from this study suggested that and its metabolites (especially the meroterpenoids) may be potential functional food ingredients for the antioxidation and prevention of neurogenerative diseases.
Topics: Antioxidants; Cell Line, Tumor; Dose-Response Relationship, Drug; Drugs, Chinese Herbal; Humans; Molecular Structure; Neuroprotective Agents; Reishi; Terpenes; Triterpenes
PubMed: 31795252
DOI: 10.3390/molecules24234353 -
International Journal of Molecular... Oct 2021Sarcoidosis is a rare, systemic inflammatory disease whose diagnosis and management can pose a challenge for clinicians and specialists. Scientific knowledge on the... (Review)
Review
Sarcoidosis is a rare, systemic inflammatory disease whose diagnosis and management can pose a challenge for clinicians and specialists. Scientific knowledge on the molecular pathways that drive its development is still lacking, with no standardized therapies available and insufficient strategies to predict patient outcome. In recent years, oxidative stress has been highlighted as an important factor in the pathogenesis of sarcoidosis, involving several enzymes and molecules in the mechanism of the disease. This review presents current data on the role of oxidative stress in sarcoidosis and its interaction with inflammation, as well as the application of antioxidative therapy in the disease.
Topics: Animals; Antioxidants; Humans; Lung; Oxidative Stress; Sarcoidosis
PubMed: 34769145
DOI: 10.3390/ijms222111712 -
Marine Drugs Nov 2019Marine-derived antioxidant polysaccharides have aroused extensive attention because of their potential nutritional and therapeutic benefits. However, the comprehensive... (Review)
Review
Marine-derived antioxidant polysaccharides have aroused extensive attention because of their potential nutritional and therapeutic benefits. However, the comprehensive comparison of identified marine-derived antioxidant polysaccharides is still inaccessible, which would facilitate the discovery of more efficient antioxidants from marine organisms. Thus, this review summarizes the sources, chemical composition, structural characteristics, and antioxidant capacity of marine antioxidant polysaccharides, as well as their protective in vivo effects mediated by antioxidative stress reported in the last few years (2013-2019), and especially highlights the dominant role of marine algae as antioxidant polysaccharide source. In addition, the relationships between the chemical composition and structural characteristics of marine antioxidant polysaccharides with their antioxidant capacity were also discussed. The antioxidant activity was found to be determined by multiple factors, including molecular weight, monosaccharide composition, sulfate position and its degree.
Topics: Antioxidants; Aquatic Organisms; Humans; Monosaccharides; Polysaccharides; Structure-Activity Relationship; Sulfates
PubMed: 31795427
DOI: 10.3390/md17120674 -
IUBMB Life Jan 2022Forkhead box, class O (FOXO) family proteins are widely expressed and highly conserved transcriptional regulators that modulate cellular fuel metabolism, stress...
Forkhead box, class O (FOXO) family proteins are widely expressed and highly conserved transcriptional regulators that modulate cellular fuel metabolism, stress resistance and cell death. FOXO target genes include genes encoding antioxidant proteins, thus likely contributing to the key role FOXOs play in the cellular response to oxidative stress and supporting the cellular strategies of antioxidant defense, that is, prevention (of the formation of reactive oxygen species), interception (of reactive species prior to their reaction with cellular components), repair (of damaged biomolecules), and adaptation (i.e., the stimulation of signaling pathways allowing for the expression of protective proteins). FOXOs themselves are regulated by redox processes at several levels, including expression of FOXO genes and enzymatic as well as nonenzymatic posttranslational modifications of FOXO proteins. The latter include modifications of FOXO cysteine residues. Here, an overview is provided on (i) the contribution of FOXO target genes to cellular antioxidative strategies, and (ii) on the impact of thiol homeostasis and thiol modification on FOXO activity.
Topics: Antioxidants; Forkhead Transcription Factors; Oxidation-Reduction; Oxidative Stress; Reactive Oxygen Species
PubMed: 34423888
DOI: 10.1002/iub.2542 -
Oxidative Medicine and Cellular... 2021Reactive oxygen species (ROS) are highly reactive molecules that can oxidize proteins, lipids, and DNA. Under physiological conditions, ROS are mainly generated in the... (Review)
Review
Reactive oxygen species (ROS) are highly reactive molecules that can oxidize proteins, lipids, and DNA. Under physiological conditions, ROS are mainly generated in the mitochondria during aerobic metabolism. Under pathological conditions, excessive ROS disrupt cellular homeostasis. High levels of ROS result in severe oxidative damage to the cellular machinery. However, a low/mild level of ROS could serve as a signal to trigger cell survival mechanisms. To prevent and cope with oxidative damage to biomolecules, cells have developed various antioxidant and detoxifying mechanisms. Meanwhile, ROS can initiate autophagy, a process of self-clearance, which helps to reduce oxidative damage by engulfing and degrading oxidized substance. This review summarizes the interactions among ROS, autophagy, and antioxidant pathways. The effects of natural phytochemicals on autophagy induction, antioxidation, and dual-function are also discussed.
Topics: Antioxidants; Autophagy; Humans; Oxidation-Reduction; Reactive Oxygen Species
PubMed: 34336103
DOI: 10.1155/2021/5583215 -
Molecules (Basel, Switzerland) May 2023Loach, rich in nutrients, such as proteins, amino acids, and mineral elements, is being gradually favored by consumers. Therefore, in this study, the antioxidant...
Loach, rich in nutrients, such as proteins, amino acids, and mineral elements, is being gradually favored by consumers. Therefore, in this study, the antioxidant activity and structural characteristics of loach peptides were comprehensively analyzed. The loach protein (LAP) with a molecular weight between 150 and 3000 Da was graded by ultrafiltration and nanofiltration processes, which exhibited excellent scavenging activity against DPPH radical (IC50 2.91 ± 0.02 mg/mL), hydroxyl radical (IC50 9.95 ± 0.03 mg/mL), and superoxide anion radical (IC50 13.67 ± 0.33 mg/mL). Additionally, LAP was purified by gel filtration chromatography, and two principal components (named as LAP-I and LAP-II) were isolated. A total of 582 and 672 peptides were identified in LAP-I and LAP-II, respectively, through structural analysis. The XRD results revealed that LAP-I and LAP-II had an irregular amorphous structure. The 2D-NMR spectroscopy results suggested that LAP-I had a compact stretch conformation in the DO solution, while LAP-II had a folded conformation. Overall, the study results suggested that loach peptide could be a potential antioxidant agent and might provide valuable information for chain conformation and antioxidant mechanism research further.
Topics: Antioxidants; Protein Hydrolysates; Free Radical Scavengers; Peptides; Proteins; Superoxides
PubMed: 37298867
DOI: 10.3390/molecules28114391 -
Frontiers in Bioscience (Scholar... May 2022Chronic kidney disease is generally progressive and currently has no reliable treatment to reverse a decline in kidney function or to slow the progression of the... (Review)
Review
Chronic kidney disease is generally progressive and currently has no reliable treatment to reverse a decline in kidney function or to slow the progression of the disease. Diabetic nephropathy is one of the leading causes of end-stage kidney failure. Kidney damage in diabetic nephropathy is largely attributed to the increased oxidative stress, affecting its metabolic activity, metabolic pathways, and hemodynamic pathways. In diabetic patients, hyperglycemia causes an increase in the production of reactive oxygen species that further increase oxidative stress. These reactive oxygen species are created through a variety of pathways, providing the opportunity for treatment using anti-oxidative defense mechanisms to prevent vascular injury. This review will give an overview of oxidative stress, along with the current treatments and limitations of diabetic nephropathy. We will also discuss the potential of antioxidative therapies, with an emphasis on the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway.
Topics: Antioxidants; Diabetes Mellitus; Diabetic Nephropathies; Humans; Hyperglycemia; Kidney; Oxidative Stress; Reactive Oxygen Species
PubMed: 35730439
DOI: 10.31083/j.fbs1402014 -
Molecules (Basel, Switzerland) Jan 2018Tibetan tea (Kangzhuan) is an essential beverage of the Tibetan people. In this study, a lyophilized aqueous extract of Tibetan tea () was prepared and analyzed by HPLC....
Tibetan tea (Kangzhuan) is an essential beverage of the Tibetan people. In this study, a lyophilized aqueous extract of Tibetan tea () was prepared and analyzed by HPLC. The results suggested that there were at least five phenolic components, including gallic acid, and four catechins (i.e., (+)-catechin, (-)-catechin gallate (), (-)-epicatechin gallate (), and (-)-epigallocatechin gallate). Gallic acid, the four catechins, and were then comparatively investigated by four antioxidant assays: ferric reducing antioxidant power, 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide radical (PTIO•) scavenging, 1,1-diphenyl-2-picryl-hydrazl radical scavenging, and 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) radical scavenging assays. In these assays, LATT, along with the five phenolic components, increased their antioxidant effects in a concentration-dependent manner; however, the half maximal scavenging concentrations of were always lower than those of . Gallic acid and the four catechins were also suggested to chelate Fe based on UV-visible spectral analysis. Ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) analysis suggested that, when mixed with PTIO•, the five phenolic components could yield two types of radical adduct formation (RAF) products (i.e., tea phenolic dimers and tea phenolic-PTIO• adducts). In a flow cytometry assay, (+)-catechin and was observed to have a cytoprotective effect towards oxidative-stressed bone marrow-derived mesenchymal stem cells. Based on this evidence, we concluded that LATT possesses antioxidative or cytoprotective properties. These effects may mainly be attributed to the presence of phenolic components, including gallic acid and the four catechins. These phenolic components may undergo electron transfer, H⁺-transfer, and Fe-chelating pathways to exhibit antioxidative or cytoprotective effects. In these effects, two diastereoisomeric CG and ECG showed differences to which a steric effect from the 2-carbon may contribute. Phenolic component decay may cause RAF in the antioxidant process.
Topics: Animals; Antioxidants; Cell Survival; Chromatography, High Pressure Liquid; Cytoprotection; Flow Cytometry; Models, Molecular; Molecular Conformation; Molecular Structure; Phenols; Plant Extracts; Rats; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Tea; Tibet
PubMed: 29364183
DOI: 10.3390/molecules23020179