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1.
Physiol Plant ; 176(3): e14313, 2024.
Article En | MEDLINE | ID: mdl-38666351

Bipolaris setariae is known to cause brown stripe disease in sugarcane, resulting in significant yield losses. Silicon (Si) has the potential to enhance plant growth and biotic resistance. In this study, the impact of Si on brown stripe disease was investigated across susceptible and resistant sugarcane varieties, utilizing four Si concentrations (0, 15, 30, and 45 g per barrel of Na2SiO3·5H2O). Si significantly reduced the incidence of brown stripe disease (7.41-59.23%) and alleviated damage to sugarcane growth parameters, photosynthetic parameters, and photosynthetic pigments. Submicroscopic observations revealed that Si induced the accumulation of silicified cells in leaves, reduced spore accumulation, decreased stomatal size, and protected organelles from B. setariae damage. In addition, Si increased the activity of antioxidant enzymes (superoxide dismutase, peroxidase, and catalase), reduced reactive oxygen species production (malondialdehyde and hydrogen peroxide) and modulated the expression of genes associated with hormone signalling (PR1, TGA, AOS, AOC, LOX, PYL8, and SnRK2), leading to the accumulation of abscisic acid and jasmonic acid and inhibiting SA synthesis. Si also activated the activity of metabolism-related enzymes (polyphenol oxidase and phenylalanine ammonia lyase) and the gene expression of PAL-dependent genes (PAL, C4H, and 4CL), regulating the accumulation of metabolites, such as chlorogenic acid and lignin. The antifungal test showed that chlorogenic acid (15ug µL-1) had a significant inhibitory effect on the growth of B. setariae. This study is the first to demonstrate the inhibitory effect of Si on B. setariae in sugarcane, highlighting Si as a promising and environmentally friendly strategy for managing brown stripe disease.


Plant Diseases , Plant Growth Regulators , Reactive Oxygen Species , Saccharum , Silicon , Saccharum/drug effects , Saccharum/metabolism , Saccharum/microbiology , Saccharum/genetics , Saccharum/growth & development , Silicon/pharmacology , Silicon/metabolism , Plant Diseases/microbiology , Reactive Oxygen Species/metabolism , Plant Growth Regulators/metabolism , Antifungal Agents/pharmacology , Antifungal Agents/metabolism , Plant Leaves/metabolism , Plant Leaves/drug effects , Plant Leaves/microbiology , Plant Leaves/genetics , Ascomycota/physiology , Ascomycota/drug effects , Signal Transduction/drug effects , Photosynthesis/drug effects , Free Radical Scavengers/metabolism
2.
New Phytol ; 242(5): 2043-2058, 2024 Jun.
Article En | MEDLINE | ID: mdl-38515251

MicroRNAs are essential in plant development and stress resistance, but their specific roles in drought stress require further investigation. Here, we have uncovered that a Populus-specific microRNAs (miRNA), miR6445, targeting NAC (NAM, ATAF, and CUC) family genes, is involved in regulating drought tolerance of poplar. The expression level of miR6445 was significantly upregulated under drought stress; concomitantly, seven targeted NAC genes showed significant downregulation. Silencing the expression of miR6445 by short tandem target mimic technology significantly decreased the drought tolerance in poplar. Furthermore, 5' RACE experiments confirmed that miR6445 directly targeted NAC029. The overexpression lines of PtrNAC029 (OE-NAC029) showed increased sensitivity to drought compared with knockout lines (Crispr-NAC029), consistent with the drought-sensitive phenotype observed in miR6445-silenced strains. PtrNAC029 was further verified to directly bind to the promoters of glutathione S-transferase U23 (GSTU23) and inhibit its expression. Both Crispr-NAC029 and PtrGSTU23 overexpressing plants showed higher levels of PtrGSTU23 transcript and GST activity while accumulating less reactive oxygen species (ROS). Moreover, poplars overexpressing GSTU23 demonstrated enhanced drought tolerance. Taken together, our research reveals the crucial role of the miR6445-NAC029-GSTU23 module in enhancing poplar drought tolerance by regulating ROS homeostasis. This finding provides new molecular targets for improving the drought resistance of trees.


Adaptation, Physiological , Droughts , Gene Expression Regulation, Plant , Glutathione Transferase , MicroRNAs , Plant Proteins , Populus , Reactive Oxygen Species , Populus/genetics , Populus/physiology , Populus/enzymology , MicroRNAs/genetics , MicroRNAs/metabolism , Reactive Oxygen Species/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Glutathione Transferase/genetics , Glutathione Transferase/metabolism , Adaptation, Physiological/genetics , Plants, Genetically Modified , Stress, Physiological/genetics , Free Radical Scavengers/metabolism , Base Sequence , Genes, Plant , Promoter Regions, Genetic/genetics , Drought Resistance
3.
Biomed Pharmacother ; 148: 112763, 2022 Apr.
Article En | MEDLINE | ID: mdl-35240526

Alzheimer's disease (AD) is caused by various pathological mechanisms; therefore, it is necessary to develop drugs that simultaneously act on multiple targets. In this study, we investigated the effects of eugenitol, which has anti-amyloid ß (Aß) and anti-neuroinflammatory effects, in an AD mouse model. We found that eugenitol potently inhibited Aß plaque and oligomer formation. Moreover, eugenitol dissociated the preformed Aß plaques and reduced Aß-induced nero2a cell death. An in silico docking simulation study showed that eugenitol may interact with Aß1-42 monomers and fibrils. Eugenitol showed radical scavenging effects and potently reduced the release of proinflammatory cytokines from lipopolysaccharide-treated BV2 cells. Systemic administration of eugenitol blocked Aß aggregate-induced memory impairment in the Morris water maze test in a dose-dependent manner. In 5XFAD mice, prolonged administration of eugenitol ameliorated memory and hippocampal long-term potentiation impairment. Moreover, eugenitol significantly reduced Aß deposits and neuroinflammation in the hippocampus of 5XFAD mice. These results suggest that eugenitol, which has anti-Aß aggregation, Aß fibril dissociation, and anti-inflammatory effects, potently modulates AD-like pathologies in 5XFAD mice, and could be a promising candidate for AD therapy.


Amyloid beta-Peptides , Memory Disorders , Neuroinflammatory Diseases , Animals , Male , Mice , Alzheimer Disease/pathology , Amyloid beta-Peptides/drug effects , Cell Death/drug effects , Cell Line , Cell Survival/drug effects , Cytokines/drug effects , Disease Models, Animal , Dose-Response Relationship, Drug , Free Radical Scavengers/metabolism , Hippocampus/drug effects , Memory Disorders/pathology , Neuroinflammatory Diseases/pathology , Reactive Oxygen Species/metabolism
4.
Mar Drugs ; 20(2)2022 Feb 06.
Article En | MEDLINE | ID: mdl-35200655

As an important enzyme involved in the marine carbon cycle, alginate lyase has received extensive attention because of its excellent degradation ability on brown algae, which is widely utilized for alginate oligosaccharide preparation or bioethanol production. In comparison with endo-type alginate lyases (PL-5, PL-7, and PL-18 families), limited studies have focused on PL-17 family alginate lyases, especially for those with special characteristics. In this study, a novel PL-17 family alginate lyase, Aly23, was identified and cloned from the marine bacterium Pseudoalteromonas carrageenovora ASY5. Aly23 exhibited maximum activity at 35 °C and retained 48.93% of its highest activity at 4 °C, representing an excellent cold-adaptation property. Comparative molecular dynamics analysis was implemented to explore the structural basis for the cold-adaptation property of Aly23. Aly23 had a high substrate preference for poly ß-D-mannuronate and exhibited both endolytic and exolytic activities; its hydrolysis reaction mainly produced monosaccharides, disaccharides, and trisaccharides. Furthermore, the enzymatic hydrolyzed oligosaccharides displayed good antioxidant activities to reduce ferric and scavenge radicals, such as hydroxyl, ABTS+, and DPPH. Our work demonstrated that Aly23 is a promising cold-adapted biocatalyst for the preparation of natural antioxidants from brown algae.


Antioxidants/pharmacology , Oligosaccharides/pharmacology , Polysaccharide-Lyases/metabolism , Pseudoalteromonas/metabolism , Antioxidants/metabolism , Disaccharides/metabolism , Free Radical Scavengers/metabolism , Free Radical Scavengers/pharmacology , Hydrolysis , Molecular Dynamics Simulation , Monosaccharides/metabolism , Oligosaccharides/metabolism , Polysaccharide-Lyases/isolation & purification , Temperature , Trisaccharides/metabolism
5.
J Ethnopharmacol ; 290: 115107, 2022 May 23.
Article En | MEDLINE | ID: mdl-35176467

ETHNOPHARMACOLOGICAL RELEVANCE: Alzheimer's disease is the most common form of dementia, but its treatment options remain few and ineffective. To find new therapeutic strategies, natural products have gained interest due to their neuroprotective potential, being able to target different pathological hallmarks associated with this disorder. Several plant species are traditionally used due to their empirical neuroprotective effects and it is worth to explore their mechanism of action. AIM OF THE STUDY: This study intended to explore the neuroprotective potential of seven traditional medicinal plants, namely Scutellaria baicalensis, Ginkgo biloba, Hypericum perforatum, Curcuma longa, Lavandula angustifolia, Trigonella foenum-graecum and Rosmarinus officinalis. The safety assessment with reference to pesticides residues was also aimed. MATERIALS AND METHODS: Decoctions prepared from these species were chemically characterized by HPLC-DAD and screened for their ability to scavenge four different free radicals (DPPH•, ABTS•+, O2•‒ and •NO) and to inhibit enzymes related to neurodegeneration (cholinesterases and glycogen synthase kinase-3ß). Cell viability through MTT assay was also evaluated in two different brain cell lines, namely non-tumorigenic D3 human brain endothelial cells (hCMEC/D3) and NSC-34 motor neurons. Furthermore, and using GC, 21 pesticides residues were screened. RESULTS: Regarding chemical composition, chromatographic analysis revealed the presence of several flavonoids, phenolic acids, curcuminoids, phenolic diterpenoids, one alkaloid and one naphthodianthrone in the seven decoctions. All extracts were able to scavenge free radicals and were moderate glycogen synthase kinase-3ß inhibitors; however, they displayed weak to moderate acetylcholinesterase and butyrylcholinesterase inhibition. G. biloba and L. angustifolia decoctions were the less cytotoxic to hCMEC/D3 and NSC-34 cell lines. No pesticides residues were detected. CONCLUSIONS: The results extend the knowledge on the potential use of plant extracts to combat multifactorial disorders, giving new insights into therapeutic avenues for Alzheimer's disease.


Alzheimer Disease/pathology , Neuroprotective Agents/pharmacology , Plant Extracts/pharmacology , Plants, Medicinal/chemistry , Cell Line , Cell Survival/drug effects , Cholinesterases/drug effects , Dose-Response Relationship, Drug , Free Radical Scavengers/metabolism , Glycogen Synthase/drug effects , Humans , Medicine, Chinese Traditional/methods , Neuroprotective Agents/adverse effects , Pesticide Residues/analysis , Plant Extracts/adverse effects
6.
Oxid Med Cell Longev ; 2022: 5450421, 2022.
Article En | MEDLINE | ID: mdl-35126815

Bisphenol A (BPA) is one of the environmental endocrine disrupting toxicants and is widely used in the industry involving plastics, polycarbonate, and epoxy resins. This study was designed to investigate the toxicological effects of BPA on hematology, serum biochemistry, and histopathology of different organs of common carp (Cyprinus carpio). A total of 60 fish were procured and haphazardly divided into four groups. Each experimental group contained 15 fish. The fish retained in group A was kept as the untreated control group. Three levels of BPA 3.0, 4.5, and 6 mg/L were given to groups B, C, and D for 30 days. Result indicated significant reduction in hemoglobin (Hb), lymphocytes, packed cell volume (PCV), red blood cells (RBC), and monocytes in a dose-dependent manner as compared to the control group. However, significantly higher values of leucocytes and neutrophils were observed in the treated groups (P < 0.05). Results on serum biochemistry revealed that the quantity of glucose, cholesterol, triglycerides, urea, and creatinine levels was significantly high (P < 0.05). Our study results showed significantly (P < 0.05) increase level of oxidative stress parameters like reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) and lower values of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), peroxidase (POD) in treated groups (4.5 mg/L and 6 mg/L)) in the brain, liver, gills, and kidneys. Our study depicted significant changes in erythrocytes (pear shaped erythrocytes, leptocytes, microcytes, spherocytes, erythrocytes with broken, lobed, micronucleus, blabbed, vacuolated nucleus, and nuclear remnants) among treated groups (4.5 mg/L and 6 mg/L). Comet assay showed increased genotoxicity in different tissues including the brain, liver, gills, and kidneys in the treated fish group. Based on the results of our experiment, it can be concluded that the BPA exposure to aquatic environment is responsible for deterioration of fish health, performance leading to dysfunction of multiple vital organs.


Benzhydryl Compounds/toxicity , Brain/drug effects , Carps/blood , Carps/genetics , DNA Damage/drug effects , Endocrine Disruptors/toxicity , Gills/drug effects , Kidney/drug effects , Liver/drug effects , Oxidative Stress/drug effects , Phenols/toxicity , Signal Transduction/drug effects , Water Pollutants, Chemical/toxicity , Animals , Benzhydryl Compounds/administration & dosage , Brain/metabolism , Brain/pathology , Catalase/metabolism , Comet Assay/methods , Free Radical Scavengers/metabolism , Gills/metabolism , Gills/pathology , Hematocrit , Kidney/metabolism , Kidney/pathology , Leukocyte Count , Liver/metabolism , Liver/pathology , Phenols/administration & dosage , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolism
7.
J Chem Phys ; 156(2): 025101, 2022 Jan 14.
Article En | MEDLINE | ID: mdl-35032990

The avian compass and many other of nature's magnetoreceptive traits are widely ascribed to the protein cryptochrome. There, magnetosensitivity is thought to emerge as the spin dynamics of radicals in the applied magnetic field enters in competition with their recombination. The first and dominant model makes use of a radical pair. However, recent studies have suggested that magnetosensitivity could be markedly enhanced for a radical triad, the primary radical pair of which undergoes a spin-selective recombination reaction with a third radical. Here, we test the practicality of this supposition for the reoxidation reaction of the reduced FAD cofactor in cryptochrome, which has been implicated with light-independent magnetoreception but appears irreconcilable with the classical radical pair mechanism (RPM). Based on the available realistic cryptochrome structures, we predict the magnetosensitivity of radical triad systems comprising the flavin semiquinone, the superoxide, and a tyrosine or ascorbyl scavenger radical. We consider many hyperfine-coupled nuclear spins, the relative orientation and placement of the radicals, their coupling by the electron-electron dipolar interaction, and spin relaxation in the superoxide radical in the limit of instantaneous decoherence, which have not been comprehensively considered before. We demonstrate that these systems can provide superior magnetosensitivity under realistic conditions, with implications for dark-state cryptochrome magnetoreception and other biological magneto- and isotope-sensitive radical recombination reactions.


Anisotropy , Benzoquinones/metabolism , Cryptochromes/metabolism , Free Radical Scavengers/metabolism , Magnetic Fields , Superoxides/metabolism , Animals , Birds , Flavin-Adenine Dinucleotide/metabolism , Oxidation-Reduction
8.
J Inorg Biochem ; 229: 111727, 2022 04.
Article En | MEDLINE | ID: mdl-35093777

Five Zn(II) complexes with 3,5-dichloro-salicylaldehyde (3,5-diCl-saloH) in the absence or presence of N,N'-donor co-ligands (2,2'-bipyridine, 1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline, or 2,2'-bipyridylamine) were synthesized and formulated as [Zn(3,5-diCl-salo)2(CH3OH)2] (1) and [Zn(3,5-diCl-salo)2(N,N'-donor)] (2-5), respectively, and characterized by diverse techniques. The crystal structures of four complexes were determined by single-crystal X-ray crystallography. The ability of the compounds to scavenge 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radicals and to reduce H2O2 was investigated. In addition, their antimicrobial profile against two Gram-positive and two Gram-negative bacterial strains were investigated. The affinity of the complexes for calf-thymus DNA was examined by diverse techniques, and the DNA-binding constants of the complexes were determined. The cleavage ability of the complexes towards supercoiled circular pBR322 plasmid DNA was examined by agarose gel electrophoretic experiments. The binding of the complexes with bovine and human serum albumins was investigated in order to determine the corresponding binding constants and the binding subdomain. In order to explain the described in vitro activity of the compounds and possibly establish a rational approach in the mechanism of action, molecular docking studies were adopted on the crystal structure of E. coli and S. aureus DNA-gyrase, 5-lipoxygenase, and 5-lipoxygenase-activating protein.


Aldehydes/chemistry , Coordination Complexes/chemistry , Zinc/chemistry , Aldehydes/metabolism , Animals , Anti-Infective Agents/metabolism , Antioxidants/metabolism , Cattle , Coordination Complexes/metabolism , Crystallography, X-Ray/methods , DNA/chemistry , Escherichia coli/metabolism , Free Radical Scavengers/metabolism , Humans , Hydrogen Peroxide/chemistry , Molecular Docking Simulation , Molecular Structure , Protein Binding , Serum Albumin, Bovine/chemistry , Serum Albumin, Human/chemistry , Staphylococcus aureus/metabolism , Zinc/metabolism
9.
Biomed Pharmacother ; 146: 112555, 2022 Feb.
Article En | MEDLINE | ID: mdl-34954639

Human exposure to radiation has expanded considerably in recent years, due to a wide range of medical, agricultural, and industrial applications. Despite its beneficial utilities, radiation is also known to have a deleterious effect on cells and tissues, largely through the creation of free radicals, which cause severe damage to biological systems through processes such as DNA double/single-strand fragmentation, protein modification, and upregulation of lipid peroxidation pathways. In addition, radiation damages genetic material while inducing hereditary genotoxicity. Developing measures to counter radiation-induced damage is thus considered to be of significant importance. Considering the inherent capability of plants to survive radiative conditions, certain plants and natural compounds have been the subject of investigations to explore and harness their natural radioprotective abilities. Podophyllum hexandrum, an Indian medicinal plant with several known traditional phytotherapeutic uses, is considered in particular to be of immense therapeutic importance. Recent studies have been conducted to validate its radioprotective potential alongside discovering its protective mechanisms following γ-radiation-induced mortality and disorder in both mice and human cells. These findings show that Podophyllum and its constituents/natural compounds protect the lungs, gastrointestinal tissues, hemopoietic system, and testis by inducing DNA repair pathways, apoptosis inhibition, free radical scavenging, metal chelation, anti-oxidation and anti-inflammatory mechanisms. In this review, we have provided an updated, comprehensive summary of ionizing radiations and their impacts on biological systems, highlighting the mechanistic and radioprotective role of natural compounds from Podophyllum hexandrum.


Berberidaceae , Plant Extracts/pharmacology , Radiation-Protective Agents/pharmacology , Animals , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Apoptosis/drug effects , Cell Survival/drug effects , Chelating Agents/pharmacology , DNA Repair/drug effects , Free Radical Scavengers/metabolism , Maximum Tolerated Dose , Medicine, Traditional , Mitochondria/drug effects , Radiation-Protective Agents/chemistry
10.
Cells ; 10(12)2021 11 30.
Article En | MEDLINE | ID: mdl-34943874

Neuroglobin (Ngb), the third member of the globin family, was discovered in human and murine brains in 2000. This monomeric globin is structurally similar to myoglobin (Mb) and hemoglobin (Hb) α and ß subunits, but it hosts a bis-histidyl six-coordinated heme-Fe atom. Therefore, the heme-based reactivity of Ngb is modulated by the dissociation of the distal HisE7-heme-Fe bond, which reflects in turn the redox state of the cell. The high Ngb levels (~100-200 µM) present in the retinal ganglion cell layer and in the optic nerve facilitate the O2 buffer and delivery. In contrast, the very low levels of Ngb (~1 µM) in most tissues and organs support (pseudo-)enzymatic properties including NO/O2 metabolism, peroxynitrite and free radical scavenging, nitrite, hydroxylamine, hydrogen sulfide reduction, and the nitration of aromatic compounds. Here, structural and (pseudo-)enzymatic properties of Ngb, which are at the root of tissue and organ protection, are reviewed, envisaging a possible role in the protection from neuronal degeneration of the retina and the optic nerve.


Neuroglobin/chemistry , Neuroglobin/metabolism , Neuroprotection , Animals , Free Radical Scavengers/metabolism , Heme/metabolism , Humans , Oxidation-Reduction
11.
Food Funct ; 12(21): 10423-10431, 2021 Nov 01.
Article En | MEDLINE | ID: mdl-34596192

Yeast mannans from Saccharomyces cerevisiae (123.2 kDa, 40.5 kDa and 21.3 kDa) were prepared. The scavenging abilities of Fe2+, OH˙, and O2˙- and protective capacities against lipid peroxidation and oxidative DNA damage increased with the reduction of the molecular weights of yeast mannans. The highest scavenging abilities of Fe2+, OH˙ and O2˙- (25.32%, 70.8%, and 61.5%) were observed with YM-90, and it showed an anti-lipid peroxidation capacity of 65.82%, which was much stronger than that of vitamin C (VC), with a thiobarbituric acid-reactive substance (TBARS) inhibition rate of 80.41%. However, the highest DPPH scavenging rate (88.7%) was exhibited by YM-30. In addition, the growth-promoting effect of yeast mannans on Lactobacillus strains was further confirmed, and a 54.2% increment of Lactobacillus plantarum ZWR5 cell viability was achieved by YM-90. The results indicated the potential industrial applications of this yeast mannan technology in therapeutic and nutraceutical production.


Antioxidants/metabolism , Lactobacillus/growth & development , Lactobacillus/metabolism , Mannans/metabolism , Saccharomyces cerevisiae/metabolism , Free Radical Scavengers/metabolism , Lipid Peroxidation/drug effects , Molecular Weight , Oxidative Stress/drug effects
12.
Cell ; 184(21): 5391-5404.e17, 2021 10 14.
Article En | MEDLINE | ID: mdl-34597584

Plant immunity is activated upon pathogen perception and often affects growth and yield when it is constitutively active. How plants fine-tune immune homeostasis in their natural habitats remains elusive. Here, we discover a conserved immune suppression network in cereals that orchestrates immune homeostasis, centering on a Ca2+-sensor, RESISTANCE OF RICE TO DISEASES1 (ROD1). ROD1 promotes reactive oxygen species (ROS) scavenging by stimulating catalase activity, and its protein stability is regulated by ubiquitination. ROD1 disruption confers resistance to multiple pathogens, whereas a natural ROD1 allele prevalent in indica rice with agroecology-specific distribution enhances resistance without yield penalty. The fungal effector AvrPiz-t structurally mimics ROD1 and activates the same ROS-scavenging cascade to suppress host immunity and promote virulence. We thus reveal a molecular framework adopted by both host and pathogen that integrates Ca2+ sensing and ROS homeostasis to suppress plant immunity, suggesting a principle for breeding disease-resistant, high-yield crops.


Calcium/metabolism , Free Radical Scavengers/metabolism , Fungal Proteins/metabolism , Oryza/immunology , Plant Immunity , Plant Proteins/metabolism , Reactive Oxygen Species/metabolism , CRISPR-Cas Systems/genetics , Cell Membrane/metabolism , Disease Resistance/genetics , Models, Biological , Oryza/genetics , Plant Diseases/immunology , Plant Proteins/genetics , Protein Binding , Protein Stability , Reproduction , Species Specificity , Ubiquitin-Protein Ligases/metabolism , Ubiquitination , Zea mays/immunology
13.
Front Endocrinol (Lausanne) ; 12: 732190, 2021.
Article En | MEDLINE | ID: mdl-34671319

Myoglobin (MB) is an oxygen-binding protein usually found in cardiac myocytes and skeletal muscle fibers. It may function as a temporary storage and transport protein for O2 but could also have scavenging capacity for reactive oxygen and nitrogen species. In addition, MB has recently been identified as a hallmark in luminal breast cancer and was shown to be robustly induced under hypoxia. Cellular responses to hypoxia are regulated by the transcription factor hypoxia-inducible factor (HIF). For exploring the function of MB in breast cancer, we employed the human cell line MDA-MB-468. Cells were grown in monolayer or as 3D multicellular spheroids, which mimic the in vivo avascular tumor architecture and physiology with a heterogeneous cell population of proliferating cells in the rim and non-cycling or necrotic cells in the core region. This central necrosis was increased after MB knockdown, indicating a role for MB in hypoxic tumor regions. In addition, MB knockdown caused higher levels of HIF-1α protein after treatment with NO, which also plays an important role in cancer cell survival. MB knockdown also led to higher reactive oxygen species (ROS) levels in the cells after treatment with H2O2. To further explore the role of MB in cell survival, we performed RNA-Seq after MB knockdown and NO treatment. 1029 differentially expressed genes (DEGs), including 45 potential HIF-1 target genes, were annotated in regulatory pathways that modulate cellular function and maintenance, cell death and survival, and carbohydrate metabolism. Of these target genes, TMEFF1, TREX2, GLUT-1, MKNK-1, and RAB8B were significantly altered. Consistently, a decreased expression of GLUT-1, MKNK-1, and RAB8B after MB knockdown was confirmed by qPCR. All three genes of interest are often up regulated in cancer and correlate with a poor clinical outcome. Thus, our data indicate that myoglobin might influence the survival of breast cancer cells, possibly due to its ROS and NO scavenging properties and could be a valuable target for cancer therapy.


Breast Neoplasms/pathology , Myoglobin/physiology , Nitric Oxide/metabolism , Reactive Oxygen Species/metabolism , Breast Neoplasms/genetics , Breast Neoplasms/metabolism , Cell Survival/drug effects , Cell Survival/genetics , Female , Free Radical Scavengers/metabolism , Gene Expression Regulation, Neoplastic/drug effects , Gene Knockdown Techniques , Humans , Myoglobin/genetics , Myoglobin/metabolism , Protective Agents/metabolism , RNA, Small Interfering/pharmacology , Signal Transduction/drug effects , Signal Transduction/genetics , Tumor Cells, Cultured
14.
Molecules ; 26(20)2021 Oct 14.
Article En | MEDLINE | ID: mdl-34684798

The genus Vachellia, previously known as Acacia, belongs to the family Fabaceae, subfamily Leguminosae, which are flowering plants, commonly known as thorn trees. They are traditionally used medicinally in various countries including South Africa for the treatment of ailments such as fever, sore throat, Tuberculosis, convulsions and as sedatives. The aim of this study was to determine biochemical variations in five Vachellia species and correlate their metabolite profiles to antioxidant activity using a chemometric approach. The antioxidant activity of five Vachellia aqueous-methanolic extracts were analyzed using three methods: 2,2-di-phenyl-1-picrylhydrazyl (DPPH) radical scavenging assay, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS+) analysis and the ferric reducing antioxidant power (FRAP) assay by means of serial dilution and bioautography with the thin-layer chromatography (TLC) method. Amongst the Vachellia extracts tested, V. karroo, V. kosiensis and V. xanthophloea demonstrated the highest DPPH, ABTS+ and FRAP inhibitory activity. The antioxidant activities of DPPH were higher than those obtained by ABTS+, although these values varied among the Vachellia species. Proton nuclear magnetic resonance (1H NMR), coupled with multivariate statistical modeling tools such as principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), were performed to profile metabolites responsible for the observed activity. The OPLS-DA categorized the five Vachellia species, separating them into two groups, with V. karroo, V. kosiensis and V. xanthophloea demonstrating significantly higher radical scavenging activity than V. tortilis and V. sieberiana, which clustered together to form another group with lower radical scavenging activity. Annotation of metabolites was carried out using the ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-qTOF-MS), and it tentatively identified 23 metabolites of significance, including epigallocatechin (m/z = 305.0659), methyl gallate (m/z = 183.0294) and quercetin (m/z = 301.0358), amongst others. These results elucidated the metabolites that separated the Vachellia species from each other and demonstrated their possible free radical scavenging activities.


Acacia/metabolism , Antioxidants/metabolism , Fabaceae/metabolism , Acacia/chemistry , Acacia/classification , Antioxidants/chemistry , Biological Products/chemistry , Biological Products/metabolism , Fabaceae/chemistry , Fabaceae/classification , Free Radical Scavengers/chemistry , Free Radical Scavengers/metabolism , Magnetic Resonance Spectroscopy , Metabolome , Metabolomics , Molecular Structure , Plant Extracts/chemistry , Plant Extracts/metabolism , Plants, Medicinal/chemistry , Plants, Medicinal/classification , Plants, Medicinal/metabolism , South Africa
15.
Bioorg Med Chem Lett ; 49: 128316, 2021 10 01.
Article En | MEDLINE | ID: mdl-34391893

A series of naringenin derivatives were designed and synthesized as multifunctional anti-Alzheimer's disease (AD) agents. The results showed that these derivatives displayed moderate-to-good acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory activities at the micromolar range (IC50, 12.91 ~ 62.52 µM for AChE and 0.094 ~ 13.72 µM for BuChE). Specifically, compound 1 showed the highest inhibitory activity against BuChE with the IC50 value of (0.094 ± 0.0054) µM. A Lineweaver-Burk plot and molecular docking studies demonstrated that 1 targeted both the catalytically active site (CAS) and the peripheral anion site (PAS) of BuChE. Besides, all derivatives showed excellent hydroxyl free radicals (·OH) scavenging ability than vitamin C and cyclic voltammetry results displayed that 1 could effectively scavenge superoxide anion radical (·O2-). In addition, compound 1 displayed good metal chelating properties and had anti-Aß aggregation activities. Therefore, compound 1 might be the potential anti-AD agent for further developments.


Carbamates/pharmacology , Chelating Agents/pharmacology , Cholinesterase Inhibitors/pharmacology , Flavanones/pharmacology , Free Radical Scavengers/pharmacology , Acetylcholinesterase/chemistry , Alzheimer Disease/drug therapy , Amyloid beta-Peptides/metabolism , Animals , Butyrylcholinesterase/chemistry , Butyrylcholinesterase/metabolism , Carbamates/chemical synthesis , Carbamates/metabolism , Chelating Agents/chemical synthesis , Chelating Agents/metabolism , Cholinesterase Inhibitors/chemical synthesis , Cholinesterase Inhibitors/metabolism , Drug Design , Electrophorus , Flavanones/chemical synthesis , Flavanones/metabolism , Free Radical Scavengers/chemical synthesis , Free Radical Scavengers/metabolism , Horses , Kinetics , Molecular Docking Simulation , Molecular Structure , Peptide Fragments/metabolism , Protein Binding , Protein Multimerization/drug effects , Structure-Activity Relationship
16.
Article En | MEDLINE | ID: mdl-34339956

Ylang-ylang (YY) essential oil (EO) is distilled from the fresh-mature flowers of the Annonaceae family tropical tree Cananga odorata [Lam.] Hook. f. & Thomson, and is widely used in perfume and cosmetic industries for its fragrant character. Herein, two different metabolomic profiles obtained using high-performance thin-layer chromatography (HPTLC), applying different stains, namely 2,2-diphenyl-1-picrylhydrazyl (DPPH·) and p-anisaldehyde, were used for discrimination of 52 YY samples across geographical origins and distillation grades. The first profile is developed using the DPPH· stain based on the radical scavenging activity (RSA) of YY EOs. Results of the HPTLC-DPPH· assay confirmed that RSA of YY EOs is in proportion to the length of distillation times. Major components contributing to the RSA of YY EOs were tentatively identified as germacrene D and α-farnesene, eugenol and linalool, by gas chromatography-mass spectrometry (GC-MS) and GC-flame ionisation detector (GC-FID). The second profile was developed using the general-purpose p-anisaldehyde stain based on the general chemical composition of YY EOs. Untargeted metabolomic discrimination of YY EOs from different geographical origins was performed based on the HPTLC-p-anisaldehyde profiles, followed by principal component analysis (PCA). A discrimination and prediction model for identification of YY distillation grade was developed using PCA and partial least squares regression (PLS) based on binned HPTLC-ultraviolet (254 nm) profiles, which was successfully applied to distillation grade determination of blended YY Complete EOs.


Cananga/chemistry , Chromatography, Thin Layer/methods , Free Radical Scavengers/chemistry , Oils, Volatile/chemistry , Plant Oils/chemistry , Biphenyl Compounds/analysis , Biphenyl Compounds/metabolism , Chromatography, High Pressure Liquid , Distillation , Eugenol/analysis , Eugenol/chemistry , Eugenol/metabolism , Free Radical Scavengers/metabolism , Metabolomics , Multivariate Analysis , Oils, Volatile/metabolism , Picrates/analysis , Picrates/metabolism , Plant Oils/metabolism , Sesquiterpenes/analysis , Sesquiterpenes/chemistry , Sesquiterpenes/metabolism
17.
ACS Appl Mater Interfaces ; 13(33): 39126-39134, 2021 Aug 25.
Article En | MEDLINE | ID: mdl-34383476

The usage of exogenous antioxidant materials to relieve oxidative stress offers an important strategy for the therapy of oxidative stress-induced injuries. However, the fabrication processes toward the antioxidant materials usually require the involvement of extra metal ions and organic agents, as well as sophisticated purification steps, which might cause tremendous environmental stress and induce unpredictable side effects in vivo. To address these issues, herein, we proposed a novel strategy to fabricate green nanoparticles for efficiently modulating oxidative stress, which was facilely prepared from tea polyphenol extracts (originated from green tea) via a green enzymatic polymerization-based chemistry method. The resulting nanoparticles possessed a uniform spherical morphology and good stability in water and biomedium and demonstrated excellent radical scavenging properties. These nanoparticle scavengers could effectively prevent intracellular oxidative damage, accelerate wound recovery, and protect the kidneys from reactive oxygen species damaging in the acute kidney injury model. We hope this work will inspire the further development of more types of green nanoparticles for antioxidant therapies via similar synthetic strategies using green biomass materials.


Acute Kidney Injury/prevention & control , Antioxidants/chemistry , Nanoparticles/chemistry , Oxidative Stress/drug effects , Polyphenols/chemistry , Tea/chemistry , 3T3 Cells , A549 Cells , Animals , Antioxidants/pharmacology , Catechols/chemistry , Cell Survival/drug effects , Female , Free Radical Scavengers/metabolism , Green Chemistry Technology , Horseradish Peroxidase/chemistry , Human Umbilical Vein Endothelial Cells , Humans , Hydrogen Peroxide/chemistry , Mice , Reactive Oxygen Species/metabolism , Theranostic Nanomedicine , Wound Healing/drug effects
18.
Int J Mol Sci ; 22(16)2021 Aug 11.
Article En | MEDLINE | ID: mdl-34445329

Melatonin is registered to treat circadian rhythm sleep-wake disorders and insomnia in patients aged 55 years and over. The essential role of the circadian sleep rhythm in the deterioration of sleep quality during COVID-19 confinement and the lack of an adverse effect of melatonin on respiratory drive indicate that melatonin has the potential to be a recommended treatment for sleep disturbances related to COVID-19. This review article describes the effects of melatonin additional to its sleep-related effects, which make this drug an attractive therapeutic option for treating patients with COVID-19. The preclinical data suggest that melatonin may inhibit COVID-19 progression. It may lower the risk of the entrance of the SARS-CoV-2 virus into cells, reduce uncontrolled hyper-inflammation and the activation of immune cells, limit the damage of tissues and multiorgan failure due to the action of free radicals, and reduce ventilator-induced lung injury and the risk of disability resulting from fibrotic changes within the lungs. Melatonin may also increase the efficacy of COVID-19 vaccination. The high safety profile of melatonin and its potential anti-SARS-CoV-2 effects make this molecule a preferable drug for treating sleep disturbances in COVID-19 patients. However, randomized clinical trials are needed to verify the clinical usefulness of melatonin in the treatment of COVID-19.


COVID-19 Drug Treatment , Melatonin/pharmacology , SARS-CoV-2/drug effects , COVID-19/virology , COVID-19 Vaccines/pharmacology , Cytokines/metabolism , Free Radical Scavengers/metabolism , Humans , Melatonin/therapeutic use , Renin-Angiotensin System , Sleep Wake Disorders/drug therapy
19.
Pak J Pharm Sci ; 34(2(Supplementary)): 737-745, 2021 Mar.
Article En | MEDLINE | ID: mdl-34275809

Present study is aimed to investigate the hepatoprotective and hematopoietic effect of Typha elephantina leaves aqueous (T.E.AQ), extract in paracetamol (PCM) intoxicated rabbits. Experimental animals were divided into various groups. The blood was taken on day 7th (W1=Week 1), day 14th (W2 = week 2) and day 21st (W3 = week 3) of treatments and was analyzed for all hematological and serum biochemical markers. PCM administration caused marked increase in the levels of serum biochemical and hematological parameters. The leaves of T.E.AQ extract at dose rate 300mg/kg body weight significantly (P<0.05) reduced the elevated levels of serum biochemical and hematological indices towards normal values on third week (day 21st) of treatment while treatment in the first two weeks revealed non-significant effects even at all doses of extract. The levels of glutathione (GSH) and radical scavenging activity (RSA) were reduced and thiobarbituric acid reactive substances (TBARS) levels was high in the PCM feed animals. Administration of (T.E.AQ) extract at high dose (300mg/kg) significantly regulated and normalized these antioxidant values. The antioxidant capacity of (TE.AQ) extract, showed increase inhibition against various extract concentrations on the basis of percent scavenging of (DPPH) free radical. The histological sections of liver further supported the hepatoprotective activity of extract.


Acetaminophen/antagonists & inhibitors , Analgesics, Non-Narcotic/toxicity , Plant Extracts/therapeutic use , Plant Leaves/chemistry , Typhaceae/chemistry , Acetaminophen/toxicity , Animals , Dose-Response Relationship, Drug , Free Radical Scavengers/metabolism , Glutathione/metabolism , Liver/drug effects , Liver/metabolism , Male , Rabbits
20.
J Inorg Biochem ; 223: 111534, 2021 10.
Article En | MEDLINE | ID: mdl-34273715

The reaction of the dioxouranium(VI) ion with a series of non-steroidal anti-inflammatory drugs (NSAIDs), namely mefenamic acid, indomethacin, diclofenac, diflunisal and tolfenamic acid, as ligands in the absence or presence of diverse N,N'-donors (1,10-phenanthroline,2,2'-bipyridine or 2,2'-bipyridylamine) as co-ligands led to the formation of ten complexes bearing the formulas [UO2(NSAID-O,O')2(O-donor)2] or [UO2(NSAID-O,O')2(N,N'-donor)], respectively. The complexes were characterized with diverse spectroscopic techniques and the crystal structures of three complexes were determined by single-crystal X-ray crystallography. The biological profile of the resultant complexes was assessed in vitro and in silico. The in vitro studies include their antioxidant properties (ability to scavenge free radicals 1,1-diphenyl-picrylhydrazyl and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) and to reduce H2O2), their interaction with DNA (linear calf-thymus DNA or supercoiled circular pBR322 plasmid DNA) and their affinity for serum albumins (bovine and human serum albumin). In silico molecular docking calculations were performed regarding the behavior of the complexes towards DNA and their binding to both albumins.


Anti-Inflammatory Agents, Non-Steroidal/chemistry , Coordination Complexes/chemistry , Free Radical Scavengers/chemistry , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Cattle , Coordination Complexes/chemical synthesis , Coordination Complexes/metabolism , DNA/chemistry , DNA/metabolism , Free Radical Scavengers/chemical synthesis , Free Radical Scavengers/metabolism , Humans , Ligands , Molecular Docking Simulation , Molecular Structure , Plasmids/chemistry , Plasmids/metabolism , Protein Binding , Serum Albumin, Bovine/chemistry , Serum Albumin, Bovine/metabolism , Serum Albumin, Human/chemistry , Serum Albumin, Human/metabolism , Uranium/chemistry
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