benzofurans and Inflammation

Inflammation and immunity play an essential role in disease pathogenesis. 3-N-Butylphthalide (NBP), a group of compounds extracted from seeds of

Topics: Anti-Inflammatory Agents; Benzofurans; Humans; Inflammation; Neuroprotective Agents

Unprecedented community containment measures were taken following the recent outbreak of COVID-19 in Italy. The aim of the study was to explore the self-reported future compliance of citizens with such measures and its relationship with potentially impactful psychological variables.. An online survey was completed by 931 people (18-76 years) distributed across the Italian territory. In addition to demographics, five dimensions were measured: self-reported compliance with containment measures over time (today, at 7, 14, 30, 60, 90, and 180 days from now) at three hypothetical risk levels (10, 50, 90% of likelihood of contracting the COVID-19), perceived risk, generalized anxiety, intolerance of uncertainty, and relevance of several psychological needs whose satisfaction is currently precluded.. The duration of containment measures plays a crucial role in tackling the spread of the disease as people will be less compliant over time. Psychological needs of citizens impacting on the compliance should be taken into account when planning an easing of the lockdown, along with interventions for protecting vulnerable groups from mental distress.. La apendicitis aguda (AA) es la urgencia quirúrgica abdominal más frecuente. No encontramos estudios específicos que evalúen el impacto de la pandemia causada por el coronavirus 2 (SARS-Cov-2) sobre la AA y su tratamiento quirúrgico. Analizamos la influencia de esta nueva patología sobre la AA.. Estudio observacional retrospectivo en pacientes intervenidos por AA desde enero hasta abril de 2020. Fueron clasificados según el momento de la apendicectomía, antes de la declaración del estado de alarma (Pre-COVID19) y después de la declaración del estado de alarma (Post-COVID19) en España. Se evaluaron variables demográficas, duración de la sintomatología, tipo de apendicitis, tiempo quirúrgico, estancia hospitalaria y complicaciones postoperatorias.. La pandemia por SARS-Cov-2 influye en el momento de diagnóstico de la apendicitis, así como en su grado de evolución y estancia hospitalaria. La peritonitis fue lo más frecuentemente observado. Una sospecha y orientación clínica más temprana, es necesaria para evitar un manejo inadecuado de este trastorno quirúrgico común.. The primary outcome is improvement in PaO. Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634).. None.. The gut barrier is crucial in cirrhosis in preventing infection-causing bacteria that normally live in the gut from accessing the liver and other organs via the bloodstream. Herein, we characterised gut inflammation by measuring different markers in stool samples from patients at different stages of cirrhosis and comparing this to healthy people. These markers, when compared with equivalent markers usually measured in blood, were found to be very different in pattern and absolute levels, suggesting that there is significant gut inflammation in cirrhosis related to different immune system pathways to that seen outside of the gut. This provides new insights into gut-specific immune disturbances that predispose to complications of cirrhosis, and emphasises that a better understanding of the gut-liver axis is necessary to develop better targeted therapies.. La surveillance de l’intervalle QT a suscité beaucoup d’intérêt durant la pandémie de la COVID-19 en raison de l’utilisation de médicaments prolongeant l’intervalle QT et les préoccupations quant à la transmission virale par les électrocardiogrammes (ECG) en série. Nous avons posé l’hypothèse que la surveillance en continu de l’intervalle QT par télémétrie était associée à une meilleure détection des épisodes de prolongation de l’intervalle QT.. Nous avons introduit la télémétrie cardiaque en continu (TCC) à l’aide d’un algorithme de surveillance automatisée de l’intervalle QT dans nos unités de COVID-19. Les mesures automatisées quotidiennes de l’intervalle QT corrigé (auto-QTc) en fonction de la fréquence cardiaque maximale ont été enregistrées. Nous avons comparé la proportion des épisodes de prolongation marquée de l’intervalle QTc (QTc long), définie par un intervalle QTc ≥ 500 ms, chez les patients montrant une suspicion de COVID-19 ou ayant la COVID-19 qui avaient été admis avant et après la mise en place de la TCC (groupe témoin. La surveillance en continu de l’intervalle QT est supérieure à la norme de soins dans la détection des épisodes de QTc long et exige peu d’ECG. La réponse clinique aux épisodes de QTc long est sous-optimale.. Exposure to a model wildfire air pollution source modifies cardiovascular responses to HC challenge, suggesting air pollution sensitizes the body to systemic triggers.. Though the majority of HIV-infected adults who were on HAART had shown viral suppression, the rate of suppression was sub-optimal according to the UNAIDS 90-90-90 target to help end the AIDS pandemic by 2020. Nonetheless, the rate of immunological recovery in the study cohort was low. Hence, early initiation of HAART should be strengthened to achieve good virological suppression and immunological recovery.. Dust in Egyptian laying hen houses contains high concentrations of microorganisms and endotoxins, which might impair the health of birds and farmers when inhaled. Furthermore, laying hens in Egypt seem to be a reservoir for ESBL-producing Enterobacteriaceae. Thus, farmers are at risk of exposure to ESBL-producing bacteria, and colonized hens might transmit these bacteria into the food chain.. The lack of significant differences in the absolute changes and relative ratios of injury and repair biomarkers by contrast-associated AKI status suggests that the majority of mild contrast-associated AKI cases may be driven by hemodynamic changes at the kidney.. Most comparisons for different outcomes are based on very few studies, mostly low-powered, with an overall low CoE. Thus, the available evidence is considered insufficient to either support or refute CH effectiveness or to recommend one ICM over another. Therefore, further well-designed, larger RCTs are required.. PROSPERO database Identifier: CRD42016041953.. Untouched root canal at cross-section perimeter, the Hero 642 system showed 41.44% ± 5.62% and Reciproc R40 58.67% ± 12.39% without contact with instruments. Regarding the untouched area, Hero 642 system showed 22.78% ± 6.42% and Reciproc R40 34.35% ± 8.52%. Neither instrument achieved complete cross-sectional root canal debridement. Hero 642 system rotary taper 0.02 instruments achieved significant greater wall contact perimeter and area compared to reciprocate the Reciproc R40 taper 0.06 instrument.. Hero 642 achieved higher wall contact perimeter and area but, regardless of instrument size and taper, vital pulp during. The functional properties of the main mechanisms involved in the control of muscle Ca. This study showed that the anti-inflammatory effect of the iron-responsive product DHA in arthritis can be monitored by an iron-like radioactive tracer (. Attenuated vascular reactivity during pregnancy suggests that the systemic vasodilatory state partially depletes nitric oxide bioavailability. Preliminary data support the potential for MRI to identify vascular dysfunction in vivo that underlies PE. Level of Evidence 2 Technical Efficacy Stage 1 J. MAGN. RESON. IMAGING 2021;53:447-455.. La evaluación de riesgo es importante para predecir los resultados postoperatorios en pacientes con cáncer gastroesofágico. Este estudio de cohortes tuvo como objetivo evaluar los cambios en la composición corporal durante la quimioterapia neoadyuvante e investigar su asociación con complicaciones postoperatorias. MÉTODOS: Los pacientes consecutivos con cáncer gastroesofágico sometidos a quimioterapia neoadyuvante y cirugía con intención curativa entre 2016 y 2019, identificados a partir de una base de datos específica, se incluyeron en el estudio. Se utilizaron las imágenes de tomografía computarizada, antes y después de la quimioterapia neoadyuvante, para evaluar el índice de masa muscular esquelética, la sarcopenia y el índice de grasa visceral y subcutánea.. In this in vitro premature infant lung model, HF oscillation of BCPAP was associated with improved CO. Our results showed that HPC significantly promotes neurogenesis after MCAO and ameliorates neuronal injury.. Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis.. These findings indicate that Tetrapleura tetraptera fruit has a protective potential against stroke through modulation of redox and electrolyte imbalances, and attenuation of neurotransmitter dysregulation and other neurochemical dysfunctions. Tetrapleura tetraptera fruit could be a promising source for the discovery of bioactives for stroke therapy.

Topics: 3T3-L1 Cells; A Kinase Anchor Proteins; Acetates; Achilles Tendon; Acute Kidney Injury; Acute Pain; Acyclic Monoterpenes; Adenine Nucleotides; Adhesins, Escherichia coli; Adipocytes; Adipocytes, Brown; Adipogenesis; Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Adsorption; Adult; Aeromonas hydrophila; Africa; Aged; Aged, 80 and over; Agrobacterium tumefaciens; Air; Air Pollutants; Air Pollution; Air Pollution, Indoor; Algorithms; Alkaloids; Alkynes; Allosteric Regulation; Amines; Amino Acid Sequence; Amino Acids; Amino Acids, Branched-Chain; Aminoisobutyric Acids; Aminopyridines; Amyotrophic Lateral Sclerosis; Anaerobic Threshold; Angiography; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animal Distribution; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Ankle Joint; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Inflammatory Agents; Antibodies, Bacterial; Antifungal Agents; Antimalarials; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Antiretroviral Therapy, Highly Active; Antiviral Agents; Aotidae; Apelin; Apoptosis; Arabidopsis Proteins; Argentina; Arginine; Artemisinins; Arthritis, Experimental; Arthritis, Rheumatoid; Arthroscopy; Aspergillus; Aspergillus niger; Asteraceae; Asthma; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; Auditory Cortex; Autoantibodies; Autophagy; Bacteria; Bacterial Infections; Bacterial Proteins; Bacterial Typing Techniques; Base Composition; Base Sequence; Basketball; Beclin-1; Benzhydryl Compounds; Benzimidazoles; Benzo(a)pyrene; Benzofurans; Benzoxazines; Bereavement; beta Catenin; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Betacoronavirus; Betaine; Binding Sites; Biofilms; Biological Assay; Biological Availability; Biological Evolution; Biomarkers; Biomechanical Phenomena; Biopolymers; Biopsy; Bismuth; Blood Glucose; Blood Platelets; Blood Pressure; Body Composition; Body Weight; Bone Marrow; Bone Marrow Cells; Bone Regeneration; Boron; Botrytis; Brain Ischemia; Brain Neoplasms; Brain-Derived Neurotrophic Factor; Brazil; Breast Neoplasms; Breath Tests; Bronchoalveolar Lavage Fluid; Burkholderia; C-Reactive Protein; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Calcification, Physiologic; Calcium; Calcium Signaling; Calorimetry, Differential Scanning; Cameroon; Camptothecin; Candida; Candida albicans; Capillaries; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Carbohydrate Conformation; Carbon; Carbon Dioxide; Carbon Isotopes; Carcinoma, Ovarian Epithelial; Cardiac Output; Cardiomyopathy, Hypertrophic; Cardiotonic Agents; Cardiovascular Diseases; Caregivers; Carps; Case-Control Studies; Catalase; Catalysis; Cats; CD4 Lymphocyte Count; Cell Culture Techniques; Cell Differentiation; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Cellulose; Centrosome; Ceratopogonidae; Chickens; Child; China; Cholera Toxin; Choline; Cholinesterases; Chromatography, High Pressure Liquid; Chromatography, Liquid; Chromatography, Micellar Electrokinetic Capillary; Chromatography, Reverse-Phase; Chronic Disease; Cinnamates; Cities; Citrates; Climate Change; Clinical Trials, Phase III as Topic; Coal; Coal Mining; Cohort Studies; Coinfection; Colchicine; Colony Count, Microbial; Colorectal Neoplasms; Coloring Agents; Common Cold; Complement Factor H; Computational Biology; Computer Simulation; Continuous Positive Airway Pressure; Contrast Media; Coordination Complexes; Coronary Artery Bypass; Coronavirus 3C Proteases; Coronavirus Infections; Coronavirus Protease Inhibitors; Corynebacterium glutamicum; Cosmetics; COVID-19; Creatinine; Cross-Sectional Studies; Crotonates; Crystallography, X-Ray; Cues; Culicidae; Culture Media; Curcuma; Cyclopentanes; Cyclopropanes; Cymbopogon; Cystine; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C19 Inhibitors; Cytokines; Databases, Genetic; Death; Dendritic Cells; Density Functional Theory; Depsides; Diabetes Mellitus, Type 2; Diamond; Diarylheptanoids; Dibenzofurans; Dibenzofurans, Polychlorinated; Diclofenac; Diet; Dietary Carbohydrates; Dietary Supplements; Diffusion Magnetic Resonance Imaging; Dioxins; Diphenylamine; Disease Outbreaks; Disease Susceptibility; Disulfides; Dithiothreitol; Dizocilpine Maleate; DNA Methylation; DNA-Binding Proteins; DNA, Bacterial; Dogs; Dose-Response Relationship, Drug; Double-Blind Method; Doublecortin Protein; Drosophila melanogaster; Droughts; Drug Carriers; Drug Combinations; Drug Delivery Systems; Drug Liberation; Drug Resistance; Drug Resistance, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Dust; Dynactin Complex; Dysferlin; Echo-Planar Imaging; Echocardiography; Edaravone; Egypt; Elasticity; Electrodes; Electrolytes; Emodin; Emtricitabine; Endometriosis; Endothelium, Vascular; Endotoxins; Energy Metabolism; Energy Transfer; Enterobacteriaceae; Enterococcus faecalis; Enterotoxigenic Escherichia coli; Environmental Monitoring; Enzyme Inhibitors; Epidemiologic Factors; Epigenesis, Genetic; Erythrocytes; Escherichia coli; Escherichia coli Infections; Escherichia coli Vaccines; Esophageal Neoplasms; Esophagectomy; Esophagogastric Junction; Esterases; Esterification; Ethanol; Ethiopia; Ethnicity; Eucalyptus; Evidence-Based Practice; Exercise; Exercise Tolerance; Extracorporeal Membrane Oxygenation; Family; Fatty Acids; Feedback; Female; Ferric Compounds; Fibrin Fibrinogen Degradation Products; Filtration; Fish Diseases; Flavonoids; Flavonols; Fluorodeoxyglucose F18; Follow-Up Studies; Food Microbiology; Food Preservation; Forests; Fossils; Free Radical Scavengers; Freund's Adjuvant; Fruit; Fungi; Gallium; Gender Identity; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Genes, Bacterial; Genes, Plant; Genetic Predisposition to Disease; Genitalia; Genotype; Glomerulonephritis, IGA; Glottis; Glucocorticoids; Glucose; Glucuronides; Glutathione Transferase; Glycogen Synthase Kinase 3 beta; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Grassland; Guinea Pigs; Half-Life; Head Kidney; Heart Atria; Heart Rate; Heart Septum; HEK293 Cells; Hematopoietic Stem Cells; Hemodynamics; Hep G2 Cells; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Hepatocytes; Hesperidin; High-Frequency Ventilation; High-Temperature Requirement A Serine Peptidase 1; Hippocampus; Hirudins; History, 20th Century; History, 21st Century; HIV Infections; Homeostasis; Hominidae; Housing, Animal; Humans; Hydrocarbons, Brominated; Hydrogen Bonding; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydroxybutyrates; Hydroxyl Radical; Hypertension; Hypothyroidism; Image Interpretation, Computer-Assisted; Immunoconjugates; Immunogenic Cell Death; Indoles; Infant, Newborn; Infant, Premature; Infarction, Middle Cerebral Artery; Inflammation; Inflammation Mediators; Infrared Rays; Inhibitory Concentration 50; Injections, Intravenous; Interferon-gamma; Interleukin-23; Interleukin-4; Interleukin-6; Intermediate Filaments; Intermittent Claudication; Intestine, Small; Iridoid Glucosides; Iridoids; Iron; Isomerism; Isotope Labeling; Isoxazoles; Itraconazole; Kelch-Like ECH-Associated Protein 1; Ketoprofen; Kidney Failure, Chronic; Kinetics; Klebsiella pneumoniae; Lactams, Macrocyclic; Lactobacillus; Lactulose; Lakes; Lamivudine; Laparoscopy; Laparotomy; Laryngoscopy; Leucine; Limit of Detection; Linear Models; Lipid A; Lipopolysaccharides; Listeria monocytogenes; Liver; Liver Cirrhosis; Logistic Models; Longitudinal Studies; Losartan; Low Back Pain; Lung; Lupinus; Lupus Erythematosus, Systemic; Machine Learning; Macular Degeneration; Madin Darby Canine Kidney Cells; Magnetic Phenomena; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Magnetics; Malaria, Falciparum; Male; Mannans; MAP Kinase Signaling System; Mass Spectrometry; Melatonin; Membrane Glycoproteins; Membrane Proteins; Meniscectomy; Menisci, Tibial; Mephenytoin; Mesenchymal Stem Cells; Metal Nanoparticles; Metal-Organic Frameworks; Methionine; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Nude; Mice, Obese; Mice, Transgenic; Microbial Sensitivity Tests; Microcirculation; MicroRNAs; Microscopy, Video; Microtubules; Microvascular Density; Microwaves; Middle Aged; Minimally Invasive Surgical Procedures; Models, Animal; Models, Biological; Models, Molecular; Models, Theoretical; Molecular Docking Simulation; Molecular Structure; Molecular Weight; Morus; Mouth Floor; Multicenter Studies as Topic; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Muscle, Skeletal; Myocardial Ischemia; Myocardium; NAD; NADP; Nanocomposites; Nanoparticles; Naphthols; Nasal Lavage Fluid; Nasal Mucosa; Neisseria meningitidis; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasms, Experimental; Neural Stem Cells; Neuroblastoma; Neurofilament Proteins; Neurogenesis; Neurons; New York; NF-E2-Related Factor 2; NF-kappa B; Nicotine; Nitriles; Nitrogen; Nitrogen Fixation; North America; Observer Variation; Occupational Exposure; Ochrobactrum; Oils, Volatile; Olea; Oligosaccharides; Omeprazole; Open Field Test; Optimism; Oregon; Oryzias; Osmolar Concentration; Osteoarthritis; Osteoblasts; Osteogenesis; Ovarian Neoplasms; Ovariectomy; Oxadiazoles; Oxidation-Reduction; Oxidative Stress; Oxygen; Ozone; p38 Mitogen-Activated Protein Kinases; Pakistan; Pandemics; Particle Size; Particulate Matter; Patient-Centered Care; Pelargonium; Peptides; Perception; Peripheral Arterial Disease; Peroxides; Pets; Pharmaceutical Preparations; Pharmacogenetics; Phenobarbital; Phenols; Phenotype; Phosphates; Phosphatidylethanolamines; Phosphines; Phospholipids; Phosphorus; Phosphorylation; Photoacoustic Techniques; Photochemotherapy; Photosensitizing Agents; Phylogeny; Phytoestrogens; Pilot Projects; Plant Components, Aerial; Plant Extracts; Plant Immunity; Plant Leaves; Plant Oils; Plants, Medicinal; Plasmodium berghei; Plasmodium falciparum; Platelet Activation; Platelet Function Tests; Pneumonia, Viral; Poaceae; Pogostemon; Poloxamer; Poly I; Poly(ADP-ribose) Polymerase Inhibitors; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Polycyclic Compounds; Polyethylene Glycols; Polylysine; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Population Dynamics; Portasystemic Shunt, Transjugular Intrahepatic; Positron Emission Tomography Computed Tomography; Postoperative Complications; Postprandial Period; Potassium Cyanide; Predictive Value of Tests; Prefrontal Cortex; Pregnancy; Prepulse Inhibition; Prevalence; Procalcitonin; Prodrugs; Prognosis; Progression-Free Survival; Proline; Proof of Concept Study; Prospective Studies; Protein Binding; Protein Conformation; Protein Domains; Protein Folding; Protein Multimerization; Protein Sorting Signals; Protein Structure, Secondary; Proton Pump Inhibitors; Protozoan Proteins; Psychometrics; Pulse Wave Analysis; Pyridines; Pyrrolidines; Quality of Life; Quantum Dots; Quinoxalines; Quorum Sensing; Radiopharmaceuticals; Rain; Random Allocation; Randomized Controlled Trials as Topic; Rats; Rats, Sprague-Dawley; Rats, Wistar; RAW 264.7 Cells; Reactive Oxygen Species; Receptor, Angiotensin, Type 1; Receptor, PAR-1; Receptors, CXCR4; Receptors, Estrogen; Receptors, Glucocorticoid; Receptors, Interleukin-1; Receptors, Interleukin-17; Receptors, Notch; Recombinant Fusion Proteins; Recombinant Proteins; Reducing Agents; Reflex, Startle; Regional Blood Flow; Regression Analysis; Reperfusion Injury; Reproducibility of Results; Republic of Korea; Respiratory Tract Diseases; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Risk Assessment; Risk Factors; Rituximab; RNA, Messenger; RNA, Ribosomal, 16S; ROC Curve; Rosmarinic Acid; Running; Ruthenium; Rutin; Sarcolemma; Sarcoma; Sarcopenia; Sarcoplasmic Reticulum; SARS-CoV-2; Scavenger Receptors, Class A; Schools; Seasons; Seeds; Sequence Analysis, DNA; Severity of Illness Index; Sex Factors; Shock, Cardiogenic; Short Chain Dehydrogenase-Reductases; Signal Transduction; Silver; Singlet Oxygen; Sinusitis; Skin; Skin Absorption; Small Molecule Libraries; Smoke; Socioeconomic Factors; Soil; Soil Microbiology; Solid Phase Extraction; Solubility; Solvents; Spain; Spectrometry, Mass, Electrospray Ionization; Spectroscopy, Fourier Transform Infrared; Speech; Speech Perception; Spindle Poles; Spleen; Sporothrix; Staphylococcal Infections; Staphylococcus aureus; Stereoisomerism; Stomach Neoplasms; Stress, Physiological; Stroke Volume; Structure-Activity Relationship; Substrate Specificity; Sulfonamides; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Rate; T-Lymphocytes, Cytotoxic; Tandem Mass Spectrometry; Temperature; Tenofovir; Terpenes; Tetracycline; Tetrapleura; Textiles; Thermodynamics; Thiobarbituric Acid Reactive Substances; Thrombin; Thyroid Hormones; Thyroid Neoplasms; Tibial Meniscus Injuries; Time Factors; Tissue Distribution; Titanium; Toluidines; Tomography, X-Ray Computed; Tooth; Tramadol; Transcription Factor AP-1; Transcription, Genetic; Transfection; Transgender Persons; Translations; Treatment Outcome; Triglycerides; Ubiquinone; Ubiquitin-Specific Proteases; United Kingdom; United States; Up-Regulation; Vascular Stiffness; Veins; Ventricular Remodeling; Viral Load; Virulence Factors; Virus Replication; Vitis; Voice; Voice Quality; Wastewater; Water; Water Pollutants, Chemical; Water-Electrolyte Balance; Weather; Wildfires; Wnt Signaling Pathway; Wound Healing; X-Ray Diffraction; Xenograft Model Antitumor Assays; Young Adult; Zoogloea

Postoperative ileus is common and is a major clinical problem. It has been widely studied in patients and in experimental models in laboratory animals. A wide variety of treatments have been tested to prevent or modify the course of this disorder.. This review draws together information on animal studies of ileus with studies on human patients. It summarizes some of the conceptual advances made in understanding the mechanisms that underlie paralytic ileus. The treatments that have been tested in human subjects (both pharmacological and non-pharmacological) and their efficacy are summarized and graded consistent with current clinical guidelines. The review is not intended to provide a comprehensive overview of ileus, but rather a general understanding of the major clinical problems associated with it, how animal models have been useful to elucidate key mechanisms and, finally, some perspectives from both scientists and clinicians as to how we may move forward with this debilitating yet common condition.

Topics: Anesthesia, Epidural; Animals; Benzofurans; Chewing Gum; Cholinergic Agents; Contrast Media; Cyclooxygenase Inhibitors; Diatrizoate Meglumine; Digestive System Surgical Procedures; Enhanced Recovery After Surgery; Enteral Nutrition; Enteric Nervous System; Fluid Therapy; Gastrointestinal Agents; Gastrointestinal Motility; Ghrelin; Humans; Ileus; Inflammation; Intestinal Pseudo-Obstruction; Intubation, Gastrointestinal; Laparoscopy; Mast Cells; Piperidines; Postoperative Complications; Serotonin 5-HT4 Receptor Agonists; Sympathetic Nervous System; Sympatholytics

Increasing prevalence of herbal and dietary supplement-induced hepatotoxicity has been reported worldwide. Usnic acid (UA) is a well-known hepatotoxin derived from lichens. Since 2000, more than 20 incident reports have been received by the US Food and Drug Administration after intake of UA containing dietary supplement resulting in severe complications. Scientists and clinicians have been studying the cause, prevention and treatment of UA-induced hepatotoxicity. It is now known that UA decouples oxidative phosphorylation, induces adenosine triphosphate (ATP) depletion, decreases glutathione (GSH), and induces oxidative stress markedly leading to lipid peroxidation and organelle stress. In addition, experimental rat liver tissues have shown massive vacuolization associated with cellular swellings. Additionally, various signaling pathways, such as c-JNK N-terminal kinase (JNK), store-operated calcium entry, nuclear erythroid 2-related factor 2 (Nrf2), and protein kinase B/mammalian target of rapamycin (Akt/mTOR) pathways are stimulated by UA causing beneficial or harmful effects. Nevertheless, there are controversial issues, such as UA-induced inflammatory or anti-inflammatory responses, cytochrome P450 detoxifying UA into non-toxic or transforming UA into reactive metabolites, and unknown mechanism of the formation of vacuolization and membrane pore. This article focused on the previous and latest comprehensive putative mechanistic findings of UA-induced hepatotoxicity and cell death. New insights on controversial issues and future perspectives are also discussed and summarized.

Topics: Animals; Autophagy; Benzofurans; Cell Death; Chemical and Drug Induced Liver Injury; Cytochrome P-450 Enzyme System; Humans; Inflammation; Liver; Mitochondria; Oxidative Phosphorylation; Oxidative Stress

The research of alternative treatment for ischemic stroke and degenerative diseases has always been a priority in neurology. 3-N-Butylphthalide (NBP), a family of compounds initially isolated from the seeds of

Topics: Apium; Apoptosis; Benzofurans; Humans; Inflammation; Nervous System Diseases; Neuroprotective Agents; Oxidative Stress; Plant Extracts

Raxofelast, also named IRFI 016 or (+/-)5-(acetyloxy)-2,3-dihydro-4,6,7-trimethyl-2-benzofuranacetic acid, belongs to a family of novel molecules designed with the aim to maximize antioxidant potency of phenols related to Vitamin E (alpha-tocopherol). This review will focus on the antioxidant and radical scavenging activity of this new promising compound.

Topics: Animals; Antioxidants; Benzofurans; Biological Availability; Humans; Inflammation; Molecular Structure; Reperfusion Injury; Vitamin E; Wound Healing

Unprecedented community containment measures were taken following the recent outbreak of COVID-19 in Italy. The aim of the study was to explore the self-reported future compliance of citizens with such measures and its relationship with potentially impactful psychological variables.. An online survey was completed by 931 people (18-76 years) distributed across the Italian territory. In addition to demographics, five dimensions were measured: self-reported compliance with containment measures over time (today, at 7, 14, 30, 60, 90, and 180 days from now) at three hypothetical risk levels (10, 50, 90% of likelihood of contracting the COVID-19), perceived risk, generalized anxiety, intolerance of uncertainty, and relevance of several psychological needs whose satisfaction is currently precluded.. The duration of containment measures plays a crucial role in tackling the spread of the disease as people will be less compliant over time. Psychological needs of citizens impacting on the compliance should be taken into account when planning an easing of the lockdown, along with interventions for protecting vulnerable groups from mental distress.. La apendicitis aguda (AA) es la urgencia quirúrgica abdominal más frecuente. No encontramos estudios específicos que evalúen el impacto de la pandemia causada por el coronavirus 2 (SARS-Cov-2) sobre la AA y su tratamiento quirúrgico. Analizamos la influencia de esta nueva patología sobre la AA.. Estudio observacional retrospectivo en pacientes intervenidos por AA desde enero hasta abril de 2020. Fueron clasificados según el momento de la apendicectomía, antes de la declaración del estado de alarma (Pre-COVID19) y después de la declaración del estado de alarma (Post-COVID19) en España. Se evaluaron variables demográficas, duración de la sintomatología, tipo de apendicitis, tiempo quirúrgico, estancia hospitalaria y complicaciones postoperatorias.. La pandemia por SARS-Cov-2 influye en el momento de diagnóstico de la apendicitis, así como en su grado de evolución y estancia hospitalaria. La peritonitis fue lo más frecuentemente observado. Una sospecha y orientación clínica más temprana, es necesaria para evitar un manejo inadecuado de este trastorno quirúrgico común.. The primary outcome is improvement in PaO. Findings will provide timely information on the safety, efficacy, and optimal dosing of t-PA to treat moderate/severe COVID-19-induced ARDS, which can be rapidly adapted to a phase III trial (NCT04357730; FDA IND 149634).. None.. The gut barrier is crucial in cirrhosis in preventing infection-causing bacteria that normally live in the gut from accessing the liver and other organs via the bloodstream. Herein, we characterised gut inflammation by measuring different markers in stool samples from patients at different stages of cirrhosis and comparing this to healthy people. These markers, when compared with equivalent markers usually measured in blood, were found to be very different in pattern and absolute levels, suggesting that there is significant gut inflammation in cirrhosis related to different immune system pathways to that seen outside of the gut. This provides new insights into gut-specific immune disturbances that predispose to complications of cirrhosis, and emphasises that a better understanding of the gut-liver axis is necessary to develop better targeted therapies.. La surveillance de l’intervalle QT a suscité beaucoup d’intérêt durant la pandémie de la COVID-19 en raison de l’utilisation de médicaments prolongeant l’intervalle QT et les préoccupations quant à la transmission virale par les électrocardiogrammes (ECG) en série. Nous avons posé l’hypothèse que la surveillance en continu de l’intervalle QT par télémétrie était associée à une meilleure détection des épisodes de prolongation de l’intervalle QT.. Nous avons introduit la télémétrie cardiaque en continu (TCC) à l’aide d’un algorithme de surveillance automatisée de l’intervalle QT dans nos unités de COVID-19. Les mesures automatisées quotidiennes de l’intervalle QT corrigé (auto-QTc) en fonction de la fréquence cardiaque maximale ont été enregistrées. Nous avons comparé la proportion des épisodes de prolongation marquée de l’intervalle QTc (QTc long), définie par un intervalle QTc ≥ 500 ms, chez les patients montrant une suspicion de COVID-19 ou ayant la COVID-19 qui avaient été admis avant et après la mise en place de la TCC (groupe témoin. La surveillance en continu de l’intervalle QT est supérieure à la norme de soins dans la détection des épisodes de QTc long et exige peu d’ECG. La réponse clinique aux épisodes de QTc long est sous-optimale.. Exposure to a model wildfire air pollution source modifies cardiovascular responses to HC challenge, suggesting air pollution sensitizes the body to systemic triggers.. Though the majority of HIV-infected adults who were on HAART had shown viral suppression, the rate of suppression was sub-optimal according to the UNAIDS 90-90-90 target to help end the AIDS pandemic by 2020. Nonetheless, the rate of immunological recovery in the study cohort was low. Hence, early initiation of HAART should be strengthened to achieve good virological suppression and immunological recovery.. Dust in Egyptian laying hen houses contains high concentrations of microorganisms and endotoxins, which might impair the health of birds and farmers when inhaled. Furthermore, laying hens in Egypt seem to be a reservoir for ESBL-producing Enterobacteriaceae. Thus, farmers are at risk of exposure to ESBL-producing bacteria, and colonized hens might transmit these bacteria into the food chain.. The lack of significant differences in the absolute changes and relative ratios of injury and repair biomarkers by contrast-associated AKI status suggests that the majority of mild contrast-associated AKI cases may be driven by hemodynamic changes at the kidney.. Most comparisons for different outcomes are based on very few studies, mostly low-powered, with an overall low CoE. Thus, the available evidence is considered insufficient to either support or refute CH effectiveness or to recommend one ICM over another. Therefore, further well-designed, larger RCTs are required.. PROSPERO database Identifier: CRD42016041953.. Untouched root canal at cross-section perimeter, the Hero 642 system showed 41.44% ± 5.62% and Reciproc R40 58.67% ± 12.39% without contact with instruments. Regarding the untouched area, Hero 642 system showed 22.78% ± 6.42% and Reciproc R40 34.35% ± 8.52%. Neither instrument achieved complete cross-sectional root canal debridement. Hero 642 system rotary taper 0.02 instruments achieved significant greater wall contact perimeter and area compared to reciprocate the Reciproc R40 taper 0.06 instrument.. Hero 642 achieved higher wall contact perimeter and area but, regardless of instrument size and taper, vital pulp during. The functional properties of the main mechanisms involved in the control of muscle Ca. This study showed that the anti-inflammatory effect of the iron-responsive product DHA in arthritis can be monitored by an iron-like radioactive tracer (. Attenuated vascular reactivity during pregnancy suggests that the systemic vasodilatory state partially depletes nitric oxide bioavailability. Preliminary data support the potential for MRI to identify vascular dysfunction in vivo that underlies PE. Level of Evidence 2 Technical Efficacy Stage 1 J. MAGN. RESON. IMAGING 2021;53:447-455.. La evaluación de riesgo es importante para predecir los resultados postoperatorios en pacientes con cáncer gastroesofágico. Este estudio de cohortes tuvo como objetivo evaluar los cambios en la composición corporal durante la quimioterapia neoadyuvante e investigar su asociación con complicaciones postoperatorias. MÉTODOS: Los pacientes consecutivos con cáncer gastroesofágico sometidos a quimioterapia neoadyuvante y cirugía con intención curativa entre 2016 y 2019, identificados a partir de una base de datos específica, se incluyeron en el estudio. Se utilizaron las imágenes de tomografía computarizada, antes y después de la quimioterapia neoadyuvante, para evaluar el índice de masa muscular esquelética, la sarcopenia y el índice de grasa visceral y subcutánea.. In this in vitro premature infant lung model, HF oscillation of BCPAP was associated with improved CO. Our results showed that HPC significantly promotes neurogenesis after MCAO and ameliorates neuronal injury.. Inflammatory markers are highly related to signs of systemic hypoperfusion in CS. Moreover, high PCT and IL-6 levels are associated with poor prognosis.. These findings indicate that Tetrapleura tetraptera fruit has a protective potential against stroke through modulation of redox and electrolyte imbalances, and attenuation of neurotransmitter dysregulation and other neurochemical dysfunctions. Tetrapleura tetraptera fruit could be a promising source for the discovery of bioactives for stroke therapy.

Topics: 3T3-L1 Cells; A Kinase Anchor Proteins; Acetates; Achilles Tendon; Acute Kidney Injury; Acute Pain; Acyclic Monoterpenes; Adenine Nucleotides; Adhesins, Escherichia coli; Adipocytes; Adipocytes, Brown; Adipogenesis; Administration, Inhalation; Administration, Oral; Adrenal Cortex Hormones; Adsorption; Adult; Aeromonas hydrophila; Africa; Aged; Aged, 80 and over; Agrobacterium tumefaciens; Air; Air Pollutants; Air Pollution; Air Pollution, Indoor; Algorithms; Alkaloids; Alkynes; Allosteric Regulation; Amines; Amino Acid Sequence; Amino Acids; Amino Acids, Branched-Chain; Aminoisobutyric Acids; Aminopyridines; Amyotrophic Lateral Sclerosis; Anaerobic Threshold; Angiography; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animal Distribution; Animal Feed; Animal Nutritional Physiological Phenomena; Animals; Ankle Joint; Anti-Bacterial Agents; Anti-HIV Agents; Anti-Inflammatory Agents; Antibodies, Bacterial; Antifungal Agents; Antimalarials; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antioxidants; Antiretroviral Therapy, Highly Active; Antiviral Agents; Aotidae; Apelin; Apoptosis; Arabidopsis Proteins; Argentina; Arginine; Artemisinins; Arthritis, Experimental; Arthritis, Rheumatoid; Arthroscopy; Aspergillus; Aspergillus niger; Asteraceae; Asthma; ATP Binding Cassette Transporter, Subfamily B, Member 1; ATP Binding Cassette Transporter, Subfamily G, Member 2; Auditory Cortex; Autoantibodies; Autophagy; Bacteria; Bacterial Infections; Bacterial Proteins; Bacterial Typing Techniques; Base Composition; Base Sequence; Basketball; Beclin-1; Benzhydryl Compounds; Benzimidazoles; Benzo(a)pyrene; Benzofurans; Benzoxazines; Bereavement; beta Catenin; beta-Lactamase Inhibitors; beta-Lactamases; beta-Lactams; Betacoronavirus; Betaine; Binding Sites; Biofilms; Biological Assay; Biological Availability; Biological Evolution; Biomarkers; Biomechanical Phenomena; Biopolymers; Biopsy; Bismuth; Blood Glucose; Blood Platelets; Blood Pressure; Body Composition; Body Weight; Bone Marrow; Bone Marrow Cells; Bone Regeneration; Boron; Botrytis; Brain Ischemia; Brain Neoplasms; Brain-Derived Neurotrophic Factor; Brazil; Breast Neoplasms; Breath Tests; Bronchoalveolar Lavage Fluid; Burkholderia; C-Reactive Protein; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Calcification, Physiologic; Calcium; Calcium Signaling; Calorimetry, Differential Scanning; Cameroon; Camptothecin; Candida; Candida albicans; Capillaries; Carbapenem-Resistant Enterobacteriaceae; Carbapenems; Carbohydrate Conformation; Carbon; Carbon Dioxide; Carbon Isotopes; Carcinoma, Ovarian Epithelial; Cardiac Output; Cardiomyopathy, Hypertrophic; Cardiotonic Agents; Cardiovascular Diseases; Caregivers; Carps; Case-Control Studies; Catalase; Catalysis; Cats; CD4 Lymphocyte Count; Cell Culture Techniques; Cell Differentiation; Cell Line, Tumor; Cell Membrane; Cell Movement; Cell Proliferation; Cell Survival; Cells, Cultured; Cellulose; Centrosome; Ceratopogonidae; Chickens; Child; China; Cholera Toxin; Choline; Cholinesterases; Chromatography, High Pressure Liquid; Chromatography, Liquid; Chromatography, Micellar Electrokinetic Capillary; Chromatography, Reverse-Phase; Chronic Disease; Cinnamates; Cities; Citrates; Climate Change; Clinical Trials, Phase III as Topic; Coal; Coal Mining; Cohort Studies; Coinfection; Colchicine; Colony Count, Microbial; Colorectal Neoplasms; Coloring Agents; Common Cold; Complement Factor H; Computational Biology; Computer Simulation; Continuous Positive Airway Pressure; Contrast Media; Coordination Complexes; Coronary Artery Bypass; Coronavirus 3C Proteases; Coronavirus Infections; Coronavirus Protease Inhibitors; Corynebacterium glutamicum; Cosmetics; COVID-19; Creatinine; Cross-Sectional Studies; Crotonates; Crystallography, X-Ray; Cues; Culicidae; Culture Media; Curcuma; Cyclopentanes; Cyclopropanes; Cymbopogon; Cystine; Cytochrome P-450 CYP2B6; Cytochrome P-450 CYP2C19; Cytochrome P-450 CYP2C19 Inhibitors; Cytokines; Databases, Genetic; Death; Dendritic Cells; Density Functional Theory; Depsides; Diabetes Mellitus, Type 2; Diamond; Diarylheptanoids; Dibenzofurans; Dibenzofurans, Polychlorinated; Diclofenac; Diet; Dietary Carbohydrates; Dietary Supplements; Diffusion Magnetic Resonance Imaging; Dioxins; Diphenylamine; Disease Outbreaks; Disease Susceptibility; Disulfides; Dithiothreitol; Dizocilpine Maleate; DNA Methylation; DNA-Binding Proteins; DNA, Bacterial; Dogs; Dose-Response Relationship, Drug; Double-Blind Method; Doublecortin Protein; Drosophila melanogaster; Droughts; Drug Carriers; Drug Combinations; Drug Delivery Systems; Drug Liberation; Drug Resistance; Drug Resistance, Bacterial; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Dust; Dynactin Complex; Dysferlin; Echo-Planar Imaging; Echocardiography; Edaravone; Egypt; Elasticity; Electrodes; Electrolytes; Emodin; Emtricitabine; Endometriosis; Endothelium, Vascular; Endotoxins; Energy Metabolism; Energy Transfer; Enterobacteriaceae; Enterococcus faecalis; Enterotoxigenic Escherichia coli; Environmental Monitoring; Enzyme Inhibitors; Epidemiologic Factors; Epigenesis, Genetic; Erythrocytes; Escherichia coli; Escherichia coli Infections; Escherichia coli Vaccines; Esophageal Neoplasms; Esophagectomy; Esophagogastric Junction; Esterases; Esterification; Ethanol; Ethiopia; Ethnicity; Eucalyptus; Evidence-Based Practice; Exercise; Exercise Tolerance; Extracorporeal Membrane Oxygenation; Family; Fatty Acids; Feedback; Female; Ferric Compounds; Fibrin Fibrinogen Degradation Products; Filtration; Fish Diseases; Flavonoids; Flavonols; Fluorodeoxyglucose F18; Follow-Up Studies; Food Microbiology; Food Preservation; Forests; Fossils; Free Radical Scavengers; Freund's Adjuvant; Fruit; Fungi; Gallium; Gender Identity; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Gene Expression Regulation, Plant; Gene Knockdown Techniques; Genes, Bacterial; Genes, Plant; Genetic Predisposition to Disease; Genitalia; Genotype; Glomerulonephritis, IGA; Glottis; Glucocorticoids; Glucose; Glucuronides; Glutathione Transferase; Glycogen Synthase Kinase 3 beta; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Grassland; Guinea Pigs; Half-Life; Head Kidney; Heart Atria; Heart Rate; Heart Septum; HEK293 Cells; Hematopoietic Stem Cells; Hemodynamics; Hep G2 Cells; Hepacivirus; Hepatitis C; Hepatitis C, Chronic; Hepatocytes; Hesperidin; High-Frequency Ventilation; High-Temperature Requirement A Serine Peptidase 1; Hippocampus; Hirudins; History, 20th Century; History, 21st Century; HIV Infections; Homeostasis; Hominidae; Housing, Animal; Humans; Hydrocarbons, Brominated; Hydrogen Bonding; Hydrogen Peroxide; Hydrogen-Ion Concentration; Hydroxybutyrates; Hydroxyl Radical; Hypertension; Hypothyroidism; Image Interpretation, Computer-Assisted; Immunoconjugates; Immunogenic Cell Death; Indoles; Infant, Newborn; Infant, Premature; Infarction, Middle Cerebral Artery; Inflammation; Inflammation Mediators; Infrared Rays; Inhibitory Concentration 50; Injections, Intravenous; Interferon-gamma; Interleukin-23; Interleukin-4; Interleukin-6; Intermediate Filaments; Intermittent Claudication; Intestine, Small; Iridoid Glucosides; Iridoids; Iron; Isomerism; Isotope Labeling; Isoxazoles; Itraconazole; Kelch-Like ECH-Associated Protein 1; Ketoprofen; Kidney Failure, Chronic; Kinetics; Klebsiella pneumoniae; Lactams, Macrocyclic; Lactobacillus; Lactulose; Lakes; Lamivudine; Laparoscopy; Laparotomy; Laryngoscopy; Leucine; Limit of Detection; Linear Models; Lipid A; Lipopolysaccharides; Listeria monocytogenes; Liver; Liver Cirrhosis; Logistic Models; Longitudinal Studies; Losartan; Low Back Pain; Lung; Lupinus; Lupus Erythematosus, Systemic; Machine Learning; Macular Degeneration; Madin Darby Canine Kidney Cells; Magnetic Phenomena; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Magnetics; Malaria, Falciparum; Male; Mannans; MAP Kinase Signaling System; Mass Spectrometry; Melatonin; Membrane Glycoproteins; Membrane Proteins; Meniscectomy; Menisci, Tibial; Mephenytoin; Mesenchymal Stem Cells; Metal Nanoparticles; Metal-Organic Frameworks; Methionine; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Nude; Mice, Obese; Mice, Transgenic; Microbial Sensitivity Tests; Microcirculation; MicroRNAs; Microscopy, Video; Microtubules; Microvascular Density; Microwaves; Middle Aged; Minimally Invasive Surgical Procedures; Models, Animal; Models, Biological; Models, Molecular; Models, Theoretical; Molecular Docking Simulation; Molecular Structure; Molecular Weight; Morus; Mouth Floor; Multicenter Studies as Topic; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Muscle, Skeletal; Myocardial Ischemia; Myocardium; NAD; NADP; Nanocomposites; Nanoparticles; Naphthols; Nasal Lavage Fluid; Nasal Mucosa; Neisseria meningitidis; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Neoplasms, Experimental; Neural Stem Cells; Neuroblastoma; Neurofilament Proteins; Neurogenesis; Neurons; New York; NF-E2-Related Factor 2; NF-kappa B; Nicotine; Nitriles; Nitrogen; Nitrogen Fixation; North America; Observer Variation; Occupational Exposure; Ochrobactrum; Oils, Volatile; Olea; Oligosaccharides; Omeprazole; Open Field Test; Optimism; Oregon; Oryzias; Osmolar Concentration; Osteoarthritis; Osteoblasts; Osteogenesis; Ovarian Neoplasms; Ovariectomy; Oxadiazoles; Oxidation-Reduction; Oxidative Stress; Oxygen; Ozone; p38 Mitogen-Activated Protein Kinases; Pakistan; Pandemics; Particle Size; Particulate Matter; Patient-Centered Care; Pelargonium; Peptides; Perception; Peripheral Arterial Disease; Peroxides; Pets; Pharmaceutical Preparations; Pharmacogenetics; Phenobarbital; Phenols; Phenotype; Phosphates; Phosphatidylethanolamines; Phosphines; Phospholipids; Phosphorus; Phosphorylation; Photoacoustic Techniques; Photochemotherapy; Photosensitizing Agents; Phylogeny; Phytoestrogens; Pilot Projects; Plant Components, Aerial; Plant Extracts; Plant Immunity; Plant Leaves; Plant Oils; Plants, Medicinal; Plasmodium berghei; Plasmodium falciparum; Platelet Activation; Platelet Function Tests; Pneumonia, Viral; Poaceae; Pogostemon; Poloxamer; Poly I; Poly(ADP-ribose) Polymerase Inhibitors; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Polycyclic Compounds; Polyethylene Glycols; Polylysine; Polymorphism, Genetic; Polymorphism, Single Nucleotide; Population Dynamics; Portasystemic Shunt, Transjugular Intrahepatic; Positron Emission Tomography Computed Tomography; Postoperative Complications; Postprandial Period; Potassium Cyanide; Predictive Value of Tests; Prefrontal Cortex; Pregnancy; Prepulse Inhibition; Prevalence; Procalcitonin; Prodrugs; Prognosis; Progression-Free Survival; Proline; Proof of Concept Study; Prospective Studies; Protein Binding; Protein Conformation; Protein Domains; Protein Folding; Protein Multimerization; Protein Sorting Signals; Protein Structure, Secondary; Proton Pump Inhibitors; Protozoan Proteins; Psychometrics; Pulse Wave Analysis; Pyridines; Pyrrolidines; Quality of Life; Quantum Dots; Quinoxalines; Quorum Sensing; Radiopharmaceuticals; Rain; Random Allocation; Randomized Controlled Trials as Topic; Rats; Rats, Sprague-Dawley; Rats, Wistar; RAW 264.7 Cells; Reactive Oxygen Species; Receptor, Angiotensin, Type 1; Receptor, PAR-1; Receptors, CXCR4; Receptors, Estrogen; Receptors, Glucocorticoid; Receptors, Interleukin-1; Receptors, Interleukin-17; Receptors, Notch; Recombinant Fusion Proteins; Recombinant Proteins; Reducing Agents; Reflex, Startle; Regional Blood Flow; Regression Analysis; Reperfusion Injury; Reproducibility of Results; Republic of Korea; Respiratory Tract Diseases; Retrospective Studies; Reverse Transcriptase Inhibitors; Rhinitis, Allergic; Risk Assessment; Risk Factors; Rituximab; RNA, Messenger; RNA, Ribosomal, 16S; ROC Curve; Rosmarinic Acid; Running; Ruthenium; Rutin; Sarcolemma; Sarcoma; Sarcopenia; Sarcoplasmic Reticulum; SARS-CoV-2; Scavenger Receptors, Class A; Schools; Seasons; Seeds; Sequence Analysis, DNA; Severity of Illness Index; Sex Factors; Shock, Cardiogenic; Short Chain Dehydrogenase-Reductases; Signal Transduction; Silver; Singlet Oxygen; Sinusitis; Skin; Skin Absorption; Small Molecule Libraries; Smoke; Socioeconomic Factors; Soil; Soil Microbiology; Solid Phase Extraction; Solubility; Solvents; Spain; Spectrometry, Mass, Electrospray Ionization; Spectroscopy, Fourier Transform Infrared; Speech; Speech Perception; Spindle Poles; Spleen; Sporothrix; Staphylococcal Infections; Staphylococcus aureus; Stereoisomerism; Stomach Neoplasms; Stress, Physiological; Stroke Volume; Structure-Activity Relationship; Substrate Specificity; Sulfonamides; Surface Properties; Surface-Active Agents; Surveys and Questionnaires; Survival Rate; T-Lymphocytes, Cytotoxic; Tandem Mass Spectrometry; Temperature; Tenofovir; Terpenes; Tetracycline; Tetrapleura; Textiles; Thermodynamics; Thiobarbituric Acid Reactive Substances; Thrombin; Thyroid Hormones; Thyroid Neoplasms; Tibial Meniscus Injuries; Time Factors; Tissue Distribution; Titanium; Toluidines; Tomography, X-Ray Computed; Tooth; Tramadol; Transcription Factor AP-1; Transcription, Genetic; Transfection; Transgender Persons; Translations; Treatment Outcome; Triglycerides; Ubiquinone; Ubiquitin-Specific Proteases; United Kingdom; United States; Up-Regulation; Vascular Stiffness; Veins; Ventricular Remodeling; Viral Load; Virulence Factors; Virus Replication; Vitis; Voice; Voice Quality; Wastewater; Water; Water Pollutants, Chemical; Water-Electrolyte Balance; Weather; Wildfires; Wnt Signaling Pathway; Wound Healing; X-Ray Diffraction; Xenograft Model Antitumor Assays; Young Adult; Zoogloea

Vagus nerve stimulation (VNS), most likely via enteric neurons, prevents postoperative ileus (POI) by reducing activation of alpha7 nicotinic receptor (α7nAChR) positive. EFS reduced the ATP-induced Ca. Enteric neurons dampen mMφ activation, an effect mimicked by prucalopride. Preoperative, but not postoperative treatment with prucalopride prevents intestinal inflammation and shortens POI in both mice and human, indicating that preoperative administration of 5-HT4R agonists should be further evaluated as a treatment of POI.. NCT02425774.

Topics: Adult; alpha7 Nicotinic Acetylcholine Receptor; Animals; Benzofurans; Disease Models, Animal; Female; Gastrointestinal Motility; Humans; Ileus; Inflammation; Intestine, Small; Macrophages; Male; Mice; Muscle, Smooth; Pancreaticoduodenectomy; Pilot Projects; Postoperative Complications; Serotonin 5-HT4 Receptor Agonists; Treatment Outcome

To investigate the effect of Butylphthalide and Xue Shuan Tong on serum inflammatory factors and prognosis of patients with cerebral infarction. One hundred and twenty patients with acute cerebral infarction were randomly divided into control group, Butylphthalide group and Xue Shuan Tong group, with 40 patients in each group. Conventional therapy was performed in the control group; On the basis of conventional therapy, 100ml Butylphthalide intravenously twice a day was administrated among patients in Butylphthalide group; On the basis of conventional therapy, 250ml 0.9% NaCl intravenously once a day was conducted among patients in Xue Shuan Tong group. A treatment course of continuous 7 days was taken in the three groups. The serum levels of IL-2 and CGRP were detected for patients in the three groups before and after treatment. Carotid plaque thickness and size as well as intima-media thickness were detected by ultrasonic testing for patients in three groups before treatment and 90 days after follow-up. The NIHSS, Barthel and MRS scoring were performed for all the patients after 90-day follow-up to evaluate the prognosis. After treatment, differences in the levels of IL-2 and CGRP for patients in the three groups showed statistical significance (P<0.05), while the levels of IL-2 and CGRP in Xue Shuan Tong group were significantly higher than those in the other two groups (P<0.05). After 7-day treatment, plaque size and thickness in Xue Shuan Tong group and Butylphthalide group were significantly reduced, compared with those before treatment (P<0.05), but no significant differences was shown in the plaque size and thickness between Xue Shuan Tong group and Butylphthalide group (P>0.05) .The CA-IMT in Xue Shuan Tong group and Butylphthalide group was significantly reduced after treatment, and that in Butylphthalide group was significantly larger than that in Xue Shuan Tong group (P<0.05). After 90-day follow-up, NIHSS scores in Butylphthalide group were significantly less than those in the other two groups (P<0.05). After 90-day follow-up, Barthel scores in Butylphthalide group and Xue Shuan Tong group were significantly larger than those in control group (P<0.05), while differences between Butylphthalide group and Xue Shuan Tong group indicated no statistical significance (P>0.05). There were significant differences in MRS scores among patients in the three groups after 90-day follow-up (P<0.05). Butylphthalide and Xue Shuan Tong are clinically effective

Topics: Aged; Aged, 80 and over; Benzofurans; Calcitonin Gene-Related Peptide; Carotid Arteries; Carotid Intima-Media Thickness; Cerebral Infarction; Drugs, Chinese Herbal; Female; Humans; Inflammation; Interleukin-2; Male; Middle Aged; Nervous System Diseases; Plaque, Atherosclerotic; Prognosis

To investigate the efficacy of butylphthalide combined with edaravone in the treatment of acute ischemic stroke and the effect on serum inflammatory factors.. One hundred and sixty patients with acute ischemic stroke who attended the neurovascular intervention department of our hospital from May 2020 to June 2022 were enrolled as study subjects for prospective analysis and were equally divided into a control group and an experimental group using the random number table method, with 80 cases in each group. The control group was treated with edaravone injection, while the experimental group was treated with butylphthalide combined with edaravone. The disease was recorded to compare the efficacy, erythrocyte sedimentation rate, homocysteine, serum inflammatory factors including tumor necrosis factor-. The total effective rate of treatment in the experimental group was 90.0% (72/80), while that of the control group was 62.5% (50/80), the total effective rate of the experimental group was significantly higher than that of the control group, and the difference was statistically significant (. The treatment of acute ischemic stroke with butylphthalide combined with edaravone has positive significance in improving blood circulation regulation and serum inflammatory factor levels and is reliable and worthy of clinical promotion.

Topics: Benzofurans; Edaravone; Humans; Inflammation; Interleukin-6; Ischemic Stroke; Stroke

Topics: Anti-Inflammatory Agents; Antineoplastic Agents; Benzofurans; Bromine; Carcinogenesis; Cyclooxygenase 2; Humans; Inflammation; Lipopolysaccharides; Nitric Oxide; Nitric Oxide Synthase Type II; Tumor Microenvironment

Multifunctional molecules might offer better treatment of complex multifactorial neurological diseases. Monoaminergic pathways dysregulation and neuroinflammation are common convergence points in diverse neurodegenerative and neuropsychiatric disorders. Aiming to target these diseases, polypharmacological agents modulating both monoaminergic pathways and neuroinflammatory were addressed. A library of analogues of the natural product hispidol was prepared and evaluated for inhibition of monoamine oxidases (MAOs) isoforms. Several molecules emerged as selective potential MAO B inhibitors. The most promising compounds were further evaluated

Topics: Benzofurans; Benzylidene Compounds; Biological Products; Dose-Response Relationship, Drug; Down-Regulation; Drug Discovery; Humans; Inflammation; Molecular Structure; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Neurodegenerative Diseases; Structure-Activity Relationship

Topics: Animals; Antagomirs; Autophagy; Benzofurans; Glomerulonephritis, Membranous; Inflammation; Kidney; MicroRNAs; Phosphatidylinositol 3-Kinase; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction

Topics: Animals; Benzofurans; Inflammation; Mice; Myeloid Differentiation Factor 88; NLR Family, Pyrin Domain-Containing 3 Protein; NLR Proteins; Oxidative Stress; Particulate Matter; Signal Transduction; Toll-Like Receptor 4

Topics: Acetylcholinesterase; Alzheimer Disease; Amyloid beta-Peptides; Animals; Anti-Inflammatory Agents; Antioxidants; Behavior, Animal; Benzofurans; Cerebral Cortex; Cognitive Dysfunction; Disease Models, Animal; Female; Hippocampus; Inflammation; Injections, Intraventricular; Interleukin-1beta; Mice; Molecular Docking Simulation; Nootropic Agents; Peptide Fragments

The aim of the present study was to investigate the role of fraxinellone in periodontitis and identify its potential mechanisms.. Lipopolysaccharide-induced periodontal ligament stem cells (PDLSCs) was employed to simulate the periodontitis in vitro. The levels of inflammatory factors were evaluated. After treatment with fraxinellone, alkaline phosphatase activity was determined. Additionally, calcium nodules staining was evaluated by alizarin red staining and the expression of osteogenesis differentiation-associated proteins was detected using western blot analysis. Moreover, the levels of proteins in bone morphogenetic protein 2 (BMP2)/Smad pathway were measured. Subsequently, BMP2 was silenced by transfection with small hairpin RNA to explore the underlying mechanisms of fraxinellone in lipopolysaccharide-induced PDLSCs.. Lipopolysaccharide stimulation significantly upregulated the levels of inflammatory factors, which were inhibited by fraxinellone intervention. Moreover, fraxinellone notably promoted osteogenic differentiation and calcification shown by increasing levels of alkaline phosphatase, calcification and osteogenic marker proteins. Furthermore, the expression of BMP2, phosphorylated Smad1 and phosphorylated Smad5 was remarkably upregulated when fraxinellone exposure in lipopolysaccharide-induced PDLSCs. What's more, BMP2 silencing dramatically restored the effects of fraxinellone on inflammation and osteogenic differentiation of PDLSCs stimulated by lipopolysaccharide.. These data demonstrated that fraxinellone alleviates inflammation and promotes osteogenic differentiation in lipopolysaccharide-stimulated PDLSCs by regulating the BMP2/Smad pathway, providing experimental supports for the clinical application of fraxinellone in the treatment of periodontitis.

Topics: Benzofurans; Bone Morphogenetic Protein 2; Cell Differentiation; Cells, Cultured; Humans; Inflammation; Lipopolysaccharides; Osteogenesis; Periodontal Ligament; Signal Transduction; Smad Proteins; Stem Cells

Dl-3-n-butylphthalide (NBP) has been widely used to treat ischemic stroke in China. To investigate the mechanisms underlying NBP activity, we established a permanent middle cerebral artery occlusion (pMCAO) rat model and injected the rats with 4 mg/kg/d NBP for nine days. We then assessed neuroinflammation, neovascularization and nerve regeneration within the brain. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry imaging (MALDI-TOF MSI) was used to determine the phospholipid distribution, while laser ablation-inductively coupled plasma mass spectrometry imaging (LA-ICP MSI) was used to measure Foxp3, Ki-67 and pCREB levels in the brain. Immunohistochemistry was used to investigate the expression of NLR family pyrin domain containing 3 (NLRP3) and its inflammatory products, caspase-1 and interleukin-1β, in brain tissues. NBP attenuated ischemic damage and ameliorated neurological deficits in rats with pMCAO. In the ischemic brain region, NBP reduced phosphatidylethanolamine (18:0), NLRP3, caspase-1 and interleukin-1β levels, but increased levels of Foxp3, Ki-67, pCREB and several phospholipids. In molecular docking analyses, NBP bound to NLRP3, interleukin-1β, caspase-1, Foxp3, and Ki-67. These results demonstrate that NBP reduces neuroinflammation in brain tissues and promotes nerve and blood vessel regeneration, thus protecting neuromorphology and function.

Topics: Animals; Benzofurans; Brain; Caspase 1; Cyclic AMP Response Element-Binding Protein; Forkhead Transcription Factors; Infarction, Middle Cerebral Artery; Inflammation; Ischemic Stroke; Ki-67 Antigen; Molecular Docking Simulation; Neovascularization, Physiologic; Nerve Regeneration; Neuroprotective Agents; NLR Family, Pyrin Domain-Containing 3 Protein; Phospholipids; Rats; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

We previously found a lipophilic fraction of the methanol/chloroform extract of a brown alga, Eisenia nipponica, that had an antiallergic effect in a murine ear swelling test. In this study, we purified the active component from the lipophilic fraction using high performance liquid chromatography and analyzed the mass and nuclear magnetic resonance spectra. This uncovered the phlorotannin dieckol, which exhibited antiallergic effects in an ear swelling test using mice sensitized by arachidonic acid, 12-O-tetradecanoylphorbol-13-acetate, and oxazolone. Mechanistic investigations indicated that dieckol suppressed degranulation, chemical mediator release, and the expression of mRNA such as cyclooxygenase-2, interleukin-6, and tumor necrosis factor-α in rat basophilic leukemia-2H3 cells. In summary, we isolated dieckol from E. nipponica and demonstrated its antiallergic mechanisms. PRACTICAL APPLICATIONS: As the incidence of allergies increases worldwide, so too does the demand for food components with antiallergic and anti-inflammatory properties. Given this trend, we focused on a brown alga that displays a variety of bioactivities. Here, we have isolated dieckol from the antiallergic lipophilic fraction of E. nipponica and found that it possesses diverse physiological activities that may prevent lifestyle-related diseases. Consequently, dieckol or the alga containing this phlorotannin could be used as a health food ingredient to combat not only allergies, but also variety of disorders including the undesirable effects of aging.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Inflammation; Mice; Phaeophyceae; Rats

Sepsis may lead to sleep deprivation, which will promote the development of neuroinflammation and mediate the progression of sepsis-associated encephalopathy (SAE). Senkyunolide I, an active component derived from an herb medicine, has been shown to provide a sedative effect to improve sleep. However, its role in sepsis is unclear. The present study was performed to investigate whether Senkyunolide I protected against SAE in a murine model of cecal ligation and puncture (CLP). Here, we showed that Senkyunolide I treatment improved the 7-day survival rate and reduced the excessive release of cytokines including TNF-

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Benzofurans; Cecum; Cognitive Dysfunction; Disease Models, Animal; Hippocampus; Inflammation; Ligation; Male; Memory Disorders; Mice, Inbred C57BL; Microglia; Neuroprotective Agents; Punctures; Sepsis-Associated Encephalopathy; Signal Transduction; Sleep Deprivation; Survival Analysis

Evidence suggests constipation precedes motor dysfunction and is the most common gastrointestinal symptom in Parkinson's disease (PD). 5-HT4 receptor (5-HT4R) agonist prucalopride has been approved to treat chronic constipation. Here, we reported intraperitoneal injection of prucalopride for 7 days increased dopamine and decreased dopamine turnover. Prucalopride administration improved motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced PD mouse models. Prucalopride treatment also ameliorated intestinal barrier impairment and increased IL-6 release in PD model mice. However, prucalopride treatment exerted no impact on JAK2/STAT3 pathway, suggesting that prucalopride may stimulate IL-6 via JAK2/STAT3-independent pathway. In conclusion, prucalopride exerted beneficial effects in MPTP-induced Parkinson's disease mice by attenuating the loss of dopamine, improving motor dysfunction and intestinal barrier.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Benzofurans; Body Weight; Disease Models, Animal; Dopamine; Eating; Inflammation; Interleukin-6; Intestinal Mucosa; Janus Kinase 2; Male; Mice; Mice, Inbred C57BL; Motor Skills; MPTP Poisoning; Neostriatum; Parkinson Disease; Parkinson Disease, Secondary; STAT3 Transcription Factor

Renal ischemia reperfusion injury (IRI) has become a growing concern in clinical practice with high morbidity and mortality rates. There is currently no effective prophylactic regimen available to prevent its occurrence and to improve its clinical prognosis. Dl-3-n-butylphthalide (NBP) has been used for stroke treatment in China for years. Little is known about its role in preventing kidney injury.. The kidneys of male C57BL/6J mice were subjected to 33 min of ischemia followed by 24 h of reperfusion. NBP was administered by gavage prior to surgery. The reno-protective effect of NBP was evaluated by serum creatinine, kidney injury markers and renal pathological changes. Furthermore, the inflammation, oxidative stress, and apoptosis markers in kidney tissue were examined. In vitro, HK2 cells were treated prophylactically with NBP and then exposed to hypoxia/reoxygenation (H/R). Cell viability and apoptosis related protein were quantified to verify the protective effect of NBP. Pro-inflammation genes expression as well as ROS generation were further investigated also.. NBP pretreatment significantly improved renal dysfunction and alleviated pathological injury, renal inflammation response, oxidative stress and cell apoptosis. Consistently, NBP attenuated H/R induced increases in ROS, pro-inflammatory genes expression, apoptosis and cleaved caspase-3 levels in HK2 cells.. Our promising results validated for the first time that NBP could ameliorate renal IRI via attenuating inflammation, oxidative stress, and apoptosis, which indicated that NBP might be a good candidate against AKI.

Topics: Animals; Apoptosis; Benzofurans; Caspase 3; Cell Hypoxia; Cell Survival; Creatinine; Disease Models, Animal; Immunohistochemistry; Inflammation; Kidney; Male; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Oxidative Stress; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction; Reperfusion Injury

Topics: Anti-Inflammatory Agents; Benzofurans; Benzoic Acid; Biomarkers; Drug Evaluation, Preclinical; Humans; Inflammation; Naphthalenes; Purinergic P2 Receptor Antagonists; Pyrimidines; Receptors, Purinergic P2; Structure-Activity Relationship; Triazoles

Aureusidin, a naturally-occurring flavonoid, is found in various plants of Cyperaceae such as Heleocharis dulcis (Burm. f.) Trin., but its pharmacological effect and active mechanism are rarely reported. This study aimed to investigate the anti-inflammatory effect and action mechanism of Aureusidin in LPS-induced mouse macrophage RAW264.7 cells. The results suggested that lipopolysaccharide (LPS)-induced nitric oxide (NO), tumor necrosis factor-α (TNF-α) and prostaglandin E2 (PGE2) production were obviously inhibited by Aureusidin. Moreover, Aureusidin also significantly decreased the mRNA expression of various inflammatory factors in LPS-stimulated RAW264.7 cells. Furthermore, mechanistic studies showed that Aureusidin significantly inhibited nuclear transfer of nuclear factor-κB (NF-κB), while increasing the nuclear translocation of nuclear factor E2-related factor 2 (Nrf2) as well as expression of Nrf2 target genes such as heme oxygenase (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1), but the addition of the HO-1 inhibitor Sn-protoporphyrin (Snpp) significantly abolished the anti-inflammatory effect of Aureusidin in LPS-stimulated RAW264.7 cells, confirming the view that HO-1 was involved in the anti-inflammatory effect. In addition, Aureusidin increased the levels of reactive oxygen species (ROS) and mitogen-activated protein kinase (MAPK) phosphorylation in RAW264.7 cells. Antioxidant N-acetylcysteine (NAC) or three MAPK inhibitors blocked the nuclear translocation of Nrf2 and HO-1 expression induced by Aureusidin, indicating that Aureusidin activated the Nrf2/HO-1 signaling pathway through ROS and MAPKs pathways. At the same time, co-treatment with the NAC blocked the phosphorylation of MAPKs. Results from molecular docking indicated that Aureusidin inhibited the NF-κB pathway by covalently binding to NF-κB. Thus, Aureusidin exerted the anti-inflammatory activity through blocking the NF-κB signaling pathways and activating the MAPKs and Nrf2/HO-1 signaling pathways. Based on the above results, Aureusidin may be an attractive therapeutic candidate for the inflammation-related diseases.

Topics: Acetylcysteine; Animals; Anti-Inflammatory Agents; Benzofurans; Heme Oxygenase-1; Humans; Inflammation; Lipopolysaccharides; MAP Kinase Signaling System; Membrane Proteins; Mice; Molecular Docking Simulation; NF-E2-Related Factor 2; NF-kappa B; Phosphorylation; RAW 264.7 Cells; Reactive Oxygen Species

The root of Salvia miltiorrhiza f. alba (RSMA) (Lamiaceae) is used for the treatment of patients with thromboangiitis obliterans (TAO) in traditional Chinese medicine. Previously, a mixture of phenolic acids extracted from RSMA has shown significant protective effects on TAO rats.. This study investigates the inhibitory effects of salvianolic acid B on TAO induced by sodium laurate injection in rats to explore the effective constituents of RSMA in TAO treatment.. TAO rats were developed using injected sodium laurate. After treatment with ligustrazine hydrochloride (15 mg/kg) and various doses of salvianolic acid B (10, 20, 40 mg/kg) by tail intravenous injection, levels of thromboxane B. Salvianolic acid B significantly decreased the expressions of TXB. Salvianolic acid B has a protective effect on TAO rats. The mechanism may involve inhibition of thrombosis and TAO-associated inflammatory responses, which may explain the success of RSMA treatment of TAO in humans in traditional Chinese medical practice. Hence, it may be a potential drug for TAO treatment in conventional medicine.

Topics: Animals; Benzofurans; Humans; Inflammation; Lauric Acids; Male; Medicine, Chinese Traditional; Plant Roots; Rats; Rats, Wistar; Salvia miltiorrhiza; Thromboangiitis Obliterans; Thrombosis

Accumulation of tau protein aggregation plays a crucial role in neurodegenerative diseases, such as Alzheimer's disease (AD). Uncontrollable neuroinflammation and tau pathology form a vicious circle that further aggravates AD progression. Herein, we reported the synthesis of usnic acid derivatives and evaluation of their inhibitory activities against tau-aggregation and neuroinflammation. The inhibitory activity of the derivatives against the self-fibrillation of the hexapeptide AcPHF6 was initially screened by ThT fluorescence assay. Using circular dichroism and transmission electron microscopy, compound 30 showed the most potent inhibitory activity against AcPHF6 self-fibrillation. Compound 30 was further confirmed to inhibit the aggregation of full-length 2N4R tau protein by a heparin-induced mechanism. In addition, we investigated the anti-inflammatory activity of compound 30, and showed that compared with sodium usnate, it reduced NO release in LPS-stimulated mouse microglia BV2 cells. More importantly, 30 showed significant protective effects against okadaic acid-induced memory impairment in rats. Thus, 30 was a novel tau-aggregation and neuroinflammation inhibitor that represented a potential therapeutic candidate for AD.

Topics: Alzheimer Disease; Animals; Benzofurans; Cell Line, Tumor; Disease Models, Animal; Dose-Response Relationship, Drug; Humans; Inflammation; Lipopolysaccharides; Male; Maze Learning; Mice; Models, Molecular; Molecular Structure; Nitric Oxide; Protein Aggregates; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; tau Proteins

Topics: Animals; Benzofurans; Cytokines; Inflammation; Intestines; Male; Oxidative Stress; Random Allocation; Rats; Rats, Sprague-Dawley; Reperfusion Injury

Sanggenon C (SC), a natural flavonoid extracted from Cortex Mori (Sang Bai Pi), is reported to possess anti-inflammatory and antioxidant properties in hypoxia. The present study aimed to investigate the therapeutic potential and the underlying mechanisms of SC in cerebral ischemia-reperfusion (I/R) injury. A rat model of reversible middle cerebral artery occlusion (MCAO) was used to induce cerebral I/R injury in vivo, and SC was administrated intragastrically. Brain injuries were evaluated using Bederson scores, brain water content, and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. The levels of inflammatory factors and oxidative stress were examined using corresponding kits. Cell apoptosis was evaluated by TUNEL. Moreover, the expressions of apoptosis-related and RhoA/ROCK signaling-related proteins were detected through western blotting. In vitro, RhoA was overexpressed in oxygen-glucose deprivation and reperfusion (OGD/R)-induced PC12 cells to confirm the contribution of RhoA-ROCK signaling inhibition by SC to the neuroprotective effects post OGD/R. Pretreatment with SC significantly ameliorated the neurologic impairment, brain edema, and cerebral infarction post MCAO-reperfusion, associated with reductions of inflammation, oxidative stress, and cell apoptosis in the brain. Furthermore, SC remarkably downregulated the expression of RhoA/ROCK signaling-related proteins post MCAO-reperfusion in rats, while overexpression of RhoA reversed the beneficial effects of SC on protecting against inflammation and oxidative stress in OGD/R-induced PC12 cells. Taken together, these findings demonstrated that SC exerts neuroprotective effects after cerebral I/R injury via inhibiting inflammation and oxidative stress through regulating RhoA-ROCK signaling, suggesting a therapeutic potential of SC in cerebral I/R injury.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Brain Ischemia; Chromones; Dose-Response Relationship, Drug; Inflammation; Male; Oxidative Stress; PC12 Cells; Rats; Rats, Sprague-Dawley; Reperfusion Injury; rho GTP-Binding Proteins; rho-Associated Kinases

The lack of effective Alzheimer's disease treatment is becoming a challenge for researchers and prompts numerous attempts to search for and develop better therapeutic solutions. Compounds that affect several routes of the neurodegeneration cascade leading to the development of disease are of particular interest. An example of such substances is resveratrol and its synthetic and natural derivatives, which have gained popularity in recent years and show promise as a possible new therapeutic option in the approach to Alzheimer's disease treatment. In this article, the state of the art evidence on the role of resveratrol (RSV) in neuroprotection is presented; research results are summarized and the importance of resveratrol and its derivatives in the treatment of Alzheimer's disease are underlined. It also focuses on various modifications of the resveratrol molecule that should be taken into account in the design of future research on drugs against Alzheimer's disease.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Benzofurans; Blood-Brain Barrier; Central Nervous System Diseases; Humans; Inflammation; Metabolic Diseases; Neuroprotection; Oxidative Stress; Resveratrol; Stilbenes; tau Proteins

Elevated inflammation is commonly observed in depression, but whether this association is causal is not determined. Our previous basic research indicated that Dl-3-n-butylphthalide (NBP) possessed an anti-inflammatory effect. Additional recent evidence consistently suggests that depression is associated with lipid metabolism. Therefore, our study performed an untargeted lipidomics approach of ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) to reveal the potential discriminating lipid profile of the hippocampus for NBP involvement in lipopolysaccharide (LPS)-induced depression. Male Sprague-Dawley(SD) rats were randomly allocated to one of three groups (n = 6): control, LPS-induced model of depression (LPS), or NBP involvement in the LPS-induced model of depression (LPS + NBP). Statistical analysis was used to identify differential hippocampus lipids in the LPS, NBP + LPS, and control groups. Our study demonstrated that most of the differentially expressed lipid metabolites were involved in glycerophospholipid metabolism, sphingolipid metabolism, glycerolipid metabolism, and glycosylphosphatidylinositol(GPI)-anchor biosynthesis, which may partially account for the pathophysiological process of depression. However, more pre-clinical and clinical evidence is warranted to determine the extent and consistency of the role of NBP and further elucidate the pathophysiological mechanisms underlying inflammation-induced depression.

Topics: Animals; Benzofurans; Depression; Hippocampus; Inflammation; Lipid Metabolism; Lipidomics; Lipopolysaccharides; Male; Neuroprotective Agents; Rats; Rats, Sprague-Dawley

Sepsis is an infection-induced aggressive and life-threatening organ dysfunction with high morbidity and mortality worldwide. Infection-associated inflammation and coagulation promote the progression of adverse outcomes in sepsis. Here, we report that phospho-Tyr705 of STAT3 (pY-STAT3), not total STAT3, contributes to systemic inflammation and coagulopathy in sepsis.. Cecal ligation and puncture (CLP)-induced septic mice were treated with BP-1-102, Napabucasin, or vehicle control respectively and then assessed for systemic inflammation, coagulation response, lung function and survival. Human pulmonary microvascular endothelial cells (HPMECs) and Raw264.7 cells were exposed to lipopolysaccharide (LPS) with pharmacological or genetic inhibition of pY-STAT3. Cells were assessed for inflammatory and coagulant factor expression, cell function and signaling.. Pharmacological inhibition of pY-STAT3 expression by BP-1-102 reduced the proinflammatory factors, suppressed coagulation activation, attenuated lung injury, alleviated vascular leakage and improved the survival rate in septic mice. Pharmacological or genetic inhibition of pY-STAT3 diminished LPS-induced cytokine production in macrophages and protected pulmonary endothelial cells via the IL-6/JAK2/STAT3, NF-κB and MAPK signaling pathways. Moreover, the increase in procoagulant indicators induced by sepsis such as tissue factor (TF), the thrombin-antithrombin complex (TAT) and D-Dimer were down-regulated by pY-STAT3 inhibition.. Our results revealed a therapeutic role of pY-STAT3 in modulating the inflammatory response and defective coagulation during sepsis. Video Abstract.

Topics: Aminosalicylic Acids; Animals; Benzofurans; Blood Coagulation; Cecum; Cell Membrane Permeability; Endothelial Cells; Humans; Inflammation; Inflammation Mediators; Ligation; Lipopolysaccharides; Macrophages; Male; Mice; Mice, Inbred C57BL; Models, Biological; Molecular Targeted Therapy; Naphthoquinones; Phosphotyrosine; Punctures; RAW 264.7 Cells; Sepsis; STAT3 Transcription Factor; Sulfonamides; Suppression, Genetic; Survival Analysis; Thromboplastin; Toll-Like Receptor 4

Accumulating evidence suggests that inflammation is linked to multiple pathological processes and induces cellular and molecular damage through the activation of inflammatory signaling pathways, including the NF‑κB pathway. The aim of the present study was to identify natural anti‑inflammatory products that can target NF‑κB activity, in order to establish a novel therapeutic approach for inflammatory diseases. Using a 4T1 breast cancer cell line that expresses the firefly luciferase gene under the control of an NF‑κB response element, 112 natural products were tested for their anti‑inflammatory properties. Sohakuhi (Morus alba Linn. bark) extract was observed to strongly suppress NF‑κB activity without affecting cell viability. To further examine the anti‑inflammatory effect of Sohakuhi, tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL)‑induced cellular damage of human HaCaT keratinocytes was evaluated. While TRAIL triggered the phosphorylation of the p65 subunit of NF‑κB, leading to cellular damage in HaCaT cells, treatment with Sohakuhi extract protected HaCaT cells against TRAIL‑induced cellular damage. Moreover, Sohakuhi treatment also upregulated the anti‑apoptotic proteins Bcl‑xL and Bcl‑2. Importantly, through chemical fractionation of Sohakuhi extract, moracin O and P were confirmed to mediate its anti‑inflammatory effects. Collectively, the present results indicated that Sohakuhi and moracin may represent potential candidates for the development of novel anti‑inflammatory drugs.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis Regulatory Proteins; Benzofurans; Cell Line, Tumor; Cell Survival; Humans; Inflammation; Keratinocytes; Mice; Morus; NF-kappa B; Phosphorylation; Signal Transduction

Ischemic heart disease is a major cause of mortality and disability worldwide. Salvianolic acid B (Sal B) is one of the main water‑soluble components of Salvia miltiorrhiza Bge. Numerous studies have demonstrated that Sal B could exert significant anti‑inflammatory and cardiovascular protective effects; however, the underlying mechanisms remain unclear. To elucidate the association between myocardial ischemia and inflammation, and to develop effective protective drugs, a rat model of myocardial ischemia was induced using isoproterenol (ISO) and an inflammation model in H9C2 cells was induced with lipopolysaccharide + adenosine triphosphate. Both of these models were treated with different concentrations of Sal B (5, 10 and 15 mg/kg in vivo; 1, 5 and 25 µM in vitro). In vivo, the serum levels of creatine kinase isoenzyme MB, glutamic oxaloacetic transaminase and IL‑1β, the cardiac function and the mRNA expression levels of NLR family pyrin domain‑containing 3 (NLRP3) inflammasome components were evaluated using ELISAs, an electrocardiogram, hematoxylin and eosin staining and reverse transcription‑quantitative PCR, respectively. The results demonstrated that treatment with Sal B markedly alleviated the acute myocardial ischemic injury induced by hypodermic injection of ISO in rats. In vitro, the results of reactive oxygen species (ROS) detection, JC‑1 staining, western blotting and TUNEL assays showed that Sal B treatment significantly inhibited intracellular ROS production, increased the mitochondrial membrane potential, regulated the expression of mitophagy‑related proteins, inhibited the activation of the NLRP3 inflammasome and inhibited apoptosis in H9C2 cells. In conclusion, these findings indicated that Sal B exerted protective effects against myocardial ischemic injury by promoting mitophagy and maintaining mitochondrial function.

Topics: Animals; Apoptosis; Benzofurans; Cell Line; China; Disease Models, Animal; Inflammasomes; Inflammation; Ischemia; Lipopolysaccharides; Male; Mitophagy; Myocardial Ischemia; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Signal Transduction; Toll-Like Receptor 4

The lack of inclusion of comorbidities in animal models of stroke may underlie the limited development of therapy in stroke. Previous studies in mice deficient of CD36, an immune receptor, indicated its contribution to stroke-induced inflammation and injury in hyperlipidemic conditions. The current study, therefore, tested whether pharmacological inhibition of CD36 provides neuroprotection in hyperlipidemic stroke. The hyperlipidemic mice subjected to stroke showed an exacerbation of infarct size and profound brain swelling. However, post-stroke treatment with CD36 inhibitors did not reduce, and in some cases worsened, acute stroke outcome, suggesting potential benefits of elevated CD36 in the post-stroke brain in a hyperlipidemic condition. On the other hand, chronic treatment of a CD36 inhibitor prior to stroke significantly reduced stroke-induced brain swelling. There was a trend toward infarct reduction, although it did not reach statistical significance. The observed benefit of preventative CD36 inhibition is in line with previously reported smaller infarct volume and swelling in CD36 KO mice. Thus, the current findings suggest that insights gained from the genetic models should be carefully considered before the implementation of pharmacological interventions, as a potential therapeutic strategy may depend on preventative treatment or a post-stroke acute treatment paradigm.

Topics: Animals; Apolipoproteins E; Benzofurans; Brain Edema; CD36 Antigens; Disease Models, Animal; Drug Administration Schedule; Drugs, Chinese Herbal; Hyperlipidemias; Inflammation; Male; Mice, Inbred C57BL; Mice, Knockout; Protective Agents; Stroke

The present study was designed to investigate the protective effect of moracin on primary culture of nucleus pulposus cells in intervertebral disc and explore the underlying mechanism. Moracin treatment significantly inhibited the LPS-induced inflammatory cytokine accumulation (IL-1β, IL-6 and TNF-α) in nucleus pulposus cells. And moracin also dramatically decreased MDA activity, and increased the levels of SOD and CAT induced by LPS challenge. Moreover, the expressions of Nrf-2 and HO-1 were decreased and the protein levels of p-NF-κBp65, p-IκBα, p-smad-3 and TGF-β were increased by LPS challenge, which were significantly reversed after moracin treatments. Moracin treatments also decreased the levels of matrix degradation enzymes (MMP-3, MMP-13) as indicated by RT-PCR analysis. However, Nrf-2 knockdown abolished these protective effects of moracin. Together, our results demonstrated the ability of moracin to antagonize LPS-mediated inflammation in primary culture of nucleus pulposus in intervertebral disc by partly regulating the Nrf2/HO-1 and NF-κB/TGF-β pathway in nucleus pulposus cells.

Topics: Benzofurans; Heme Oxygenase (Decyclizing); Humans; Inflammation; Lipopolysaccharides; Matrix Metalloproteinase 13; Matrix Metalloproteinase 3; NF-E2-Related Factor 2; NF-kappa B; Nucleus Pulposus; Stilbenes; Transforming Growth Factor beta

The aim of this study was to investigate the effects of butylphthalide on oxidative stress and inflammatory response in rats with myocardial infarction through the protein kinase B/nuclear factor E2-related factor 2 (Akt/Nrf2) signaling pathway.. A total of 36 Sprague-Dawley rats were randomly divided into three groups, including sham group (n=12), model group (n=12) and butylphthalide group (n=12). In the sham group, the heart was exposed, and normal saline was intraperitoneally injected after the operation. In the model group, acute myocardial infarction (AMI) model was established, and normal saline was intraperitoneally injected after the operation. In the butylphthalide group, AMI model was established, and butylphthalide was intraperitoneally injected after the operation. After intervention for 4 weeks, the rats were killed, and the samples were collected. The morphology of heart tissues was observed via hematoxylin-eosin (HE) staining. The expression of nicotinamide adenine dinucleotide phosphate oxidase-1 (NOX-1) was detected via immunohistochemistry. The protein expressions of phosphorylated Akt (p-Akt) and p-Nrf2 were detected via Western blotting. Moreover, the content of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) was detected via enzyme-linked immunosorbent assay (ELISA). The messenger ribonucleic acid (mRNA) expression levels of IL-1β, TNF-α and NOX-1 were detected via quantitative Polymerase Chain reaction (qPCR). Furthermore, the apoptosis rate of the cells was detected via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.. The morphology of heart tissues was significantly damaged in the model group and butylphthalide group compared with the sham group. However, it was significantly improved in the butylphthalide group when compared with the model group. The expression level of NOX-1 increased markedly in the model group and butylphthalide group compared with the sham group (p<0.05). However, it was remarkably reduced in the butylphthalide group compared with the model group (p<0.05). Meanwhile, the protein expression levels of p-Akt and p-Nrf2 were significantly higher in the model group and butylphthalide group than those of the sham group (p<0.05). However, the protein expression levels of p-Akt and p-Nrf2 in the butylphthalide group were remarkably lower than the model group (p<0.05). The mRNA expression levels of IL-1β, TNF-α and NOX-1 were markedly higher in the model group and butylphthalide group than those of the sham group (p<0.05). However, they remarkably declined in the butylphthalide group compared with the model group (p<0.05). In addition, the content of IL-1β and TNF-α increased in the model group and butylphthalide group when compared with the sham group (p<0.05). The content of IL-1β and TNF-α in the butylphthalide group was significantly lower than the model group (p<0.05). Furthermore, the apoptosis rate was significantly higher in the model group and butylphthalide group than the sham group (p<0.05), which was significantly lower in the butylphthalide group than the model group (p<0.05).. Butylphthalide inhibits inflammatory and oxidative stress responses after AMI by regulating the Akt/Nrf2 signaling pathway, thereby inhibiting myocardial apoptosis and benefiting the morphological repair of myocardial tissues.

Topics: Animals; Benzofurans; Disease Models, Animal; Inflammation; Male; Myocardial Infarction; Neuroprotective Agents; NF-E2-Related Factor 2; Oxidative Stress; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Signal Transduction

Inflammation is an aggregate of different pathologic responses in body that leads to life threatening conditions if not combated at early stages. A variety of chemical medications from low quality to high quality are available in market for treatment of inflammation. However the side effects posed by these medications cannot be ignored. Here in our study we have shown for the first time, the anti-inflammatory effects of SBF compound that is obtained from wild mushroom species that are Acremonium sp. HKI 0230 and Coprinus echinosporus. We employed Nitric oxide determination, cell viability assay, RT-PCR and western blot analysis to check the anti-inflammatory effects of SBF. The antioxidant activity of this compound has been studied in detail in past, but our results have shown that SBF potently suppressed the Nitric oxide production (NO) without any cytotoxicity to the model cell line; RAW 264.7 cells. It also inhibited the production of major proinflammatory mediators and cytokines i.e. iNOS, COX-2, IL-1β, IL-6 and TNF-α. SBF elicited its anti-inflammatory effects via the canonical NF-κB and MAPK pathway. Taken together, our results have shown that SBF exhibits excellent anti-inflammatory activity in vitro and further experimentations may warrant its application as a commercial herbal remedy for inflammation related anomalies.

Topics: Acremonium; Animals; Anti-Inflammatory Agents; Benzofurans; Cell Line; Coprinus; Cytokines; Inflammation; Inflammation Mediators; Mice; NF-kappa B; Nitric Oxide; RAW 264.7 Cells; Signal Transduction; Spiro Compounds

Metabolic inflammatory damage, characterized by Toll-like receptor 4 (TLR4) signaling activation, is a major mechanism underlying lipotoxicity-induced

Topics: Animals; Benzofurans; Cell Line, Tumor; Diet, High-Fat; Inflammation; Insulin-Secreting Cells; Male; Mice; Obesity; Rats; Rats, Sprague-Dawley; Receptors, G-Protein-Coupled; Signal Transduction; Sulfones; Toll-Like Receptor 4; Transcription Factor RelA

Paclitaxel induces microglial activation and production of proinflammatory mediators in the dorsal horn, which contribute to the development and maintenance of central sensitization and pain behavior. MDA7, 1-([3-benzyl-3-methyl-2,3-dihydro-1-benzofuran-6-yl]carbonyl) piperidine, is a novel highly selective cannabinoid type 2 (CB2) agonist. We tested the hypothesis that activation of CB2 receptor by MDA7 modulates microglial dysregulation, suppresses the overexpression of brain-derived neurotrophic factor (BDNF) in microglia in the dorsal horn, and attenuates the central sensitization and pain behavior induced by paclitaxel. For 4 consecutice days, groups of rats randomly received saline or 1.0 mg/kg of paclitaxel daily intraperitoneally for a total cumulative dose of 4 mg/kg. MDA7 15 mg/kg intraperitoneally or vehicle were administered 15 min before administering paclitaxel for 4 days and then continued for another 10 days. Behavioral and molecular studies were performed. Paclitaxel induced the expression of CB2 receptors and production of interleukin (IL)-6 in microglia in the dorsal horn. MDA7 attenuated the expression of IL-6 and promoted the expression of IL-10. Paclitaxel induced epigenetic upregulation of IRF8 and P2X purinoceptor 4 (P2X4) in microglia and subsequently increased the expression of alpha isoform of calcium/calmodulin-dependent protein kinase II (CaMKIIα), transcriptional factors p-CREB and ΔFosB, leading to the overproduction of BDNF in microglia. Paclitaxel also upregulated the expression of glutamate receptor subunits GluR1 and NR2B, decreased the expression of K

Topics: Animals; Benzofurans; Brain-Derived Neurotrophic Factor; Cannabinoid Receptor Agonists; Central Nervous System Sensitization; Epigenesis, Genetic; Hyperalgesia; Inflammation; Male; Microglia; Neuralgia; Paclitaxel; Piperidines; Random Allocation; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB2; Spinal Cord Dorsal Horn

Topics: Benzofurans; Cholinergic Agents; Humans; Ileus; Inflammation; Neurons; Postoperative Complications; Receptors, Serotonin, 5-HT4; Serotonin 5-HT4 Receptor Agonists

The present study investigates the protective effect of napabucasin on the expression of apoptosis markers and inflammatory factors in the neuronal rat cells with post-isolation damage. The level of ROS determined by the fluorescence measurement in the neuronal rat cells with post-isolation damage was 310.21 RFU compared to 21.45 RFU in sham cell cultures. Napabucasin treatment decreased ROS level in the neuronal rat cells with post-isolation damage in dose based manner. ROS level decreased to 278.67, 203.65, 163.32 and 26.87 RFU, respectively in 1, 2, 3 and 4 μM napabucasin treated cell cultures. Treatment with napabucasin increased GSH level significantly (P < 0.05) in the neuronal rat cells with post-isolation damage. Napabucasin treatment at with 1, 2, 3 and 4 μM concentrations increased SOD activity to 2.4, 3.6, 5.1 and 6.1 U/mg, respectively. Treatment with napabucasin increased the activity of catalase in dose based manner. Napabucasin treatment increased Gpx in injured brain cells of neonatal rats. A significant (P < 0.05) increase in the activity of AChE was observed in neuronal rat cells with post-isolation damage on treatment with napabucasin. Treatment with napabucasin reduced the level of TNF-α and IL-6 significantly (P < 0.05) compared to untreated group. Napabucasin treatment decreased the expression of Bax, caspase-3 and p53 proteins in the neuronal rat cells with post-isolation damage. Napabucasin treatment protects post-isolation damage in the neuronal cells of neonatal rats by suppression of apoptosis and oxidative stress. Therefore, napabucasin can be used for the treatment of brain injury.

Topics: Animals; Apoptosis; bcl-2-Associated X Protein; Benzofurans; Brain; Brain Injuries; Caspase 3; Catalase; Dose-Response Relationship, Drug; Glutathione Peroxidase; Inflammation; Interleukin-6; Naphthoquinones; Neuroglia; Neurons; Neuroprotective Agents; Oxidative Stress; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species; Tumor Necrosis Factor-alpha; Tumor Suppressor Protein p53

Inflammasomes promote the production of pro-inflammatory cytokines, such as interleukin (IL)-1β and IL-18, which are the representative mediators of inflammation. Abnormal activation of inflammasomes leads to the development of inflammatory diseases such as acute pancreatitis (AP). In this study, we demonstrate the inhibitory effects of a new natural compound fraxinellone on inflammasome formation and examine the role of inflammasomes in a mouse model of AP. AP was induced with hourly intraperitoneal injections of supramaximal concentrations of the stable cholecystokinin analogue cerulein (50 μg/kg) for 6 h. Mice were sacrificed 6 h after the final cerulein injection. Blood and pancreas samples were obtained for further experiments. Intraperitoneal injection of fraxinellone significantly inhibited the pancreatic activation of multiple inflammasome molecules such as NACHT, LRR and PYD domains-containing protein 3 (NLRP3), PY-CARD, caspase-1, IL-18, and IL-1β during AP. In addition, fraxinellone treatment inhibited pancreatic injury, elevation in serum amylase and lipase activities, and infiltration of inflammatory cells such as neutrophils and macrophages but had no effect on pancreatic edema. To investigate whether inflammasome activation leads to the infiltration of inflammatory cells, we used parthenolide, a well-known natural inhibitor, and IL-1 receptor antagonist mice. The inhibition of inflammasome activation by pharmacological/or genetic modification restricted the infiltration of inflammatory cells, but not edema, consistent with the results observed with fraxinellone. Taken together, our study highlights fraxinellone as a natural inhibitor of inflammasomes and that inflammasome inhibition may lead to the suppression of inflammatory cells during AP.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Benzofurans; Cell Movement; Ceruletide; Disease Models, Animal; Female; Humans; Inflammasomes; Inflammation; Macrophages; Male; Mice; Mice, Inbred C57BL; Neutrophils; Pancreatitis

As Alzheimer's disease (AD) induces several cellular and molecular damages, it could be interesting to use multi-target molecules for therapeutics. We previously published that trans ε-viniferin induced the disaggregation of Aβ42 peptide and inhibited the inflammatory response in primary cellular model of AD. Here, effects of this stilbenoid were evaluated in transgenic APPswePS1dE9 mice. We report that trans ε-viniferin could go through the blood brain barrier, reduces size and density of amyloid deposits and decreases reactivity of astrocytes and microglia, after a weekly intraperitoneal injection at 10 mg/kg from 3 to 6 months of age.

Topics: Alzheimer Disease; Animals; Astrocytes; Benzofurans; Disease Models, Animal; Female; Inflammation; Male; Mice; Mice, Transgenic; Microglia; Plaque, Amyloid; Stilbenes

Acute graft-versus-host disease (aGvHD) remains lethal, even after allogeneic hematopoietic stem cell transplantation. Inflammatory responses play an important role in aGvHD. Salvianolic acid B (Sal B) has been widely reported to have a major effect on the anti-inflammatory response, but these effects in an aGvHD model have never been reported. B6 donor splenocytes were transplanted into unirradiated BDF1 recipients and liver and serum were collected on day 14 after transplantation with or without Sal B administration. We measured the expression of pro-inflammatory cytokines and chemokines and other manifestations in aGvHD mice after Sal B treatment. Sal B ameliorated liver injury in aGvHD and promoted survival in mice. Sal B treatment resulted in decreased expression of pro-inflammatory cytokines and chemokines whose expressions in liver are normally elevated by aGvHD. Furthermore, Sal B treatment also enhanced PGC-1α expression in liver tissue and HO-1 expression in nonparenchymal cells. In addition, HO-1 inhibitor abrogated the improvement of survival rate of mice with aGvHD. These results indicated that the protective effect of Sal B relies on suppressing the inflammatory response phase in the aGvHD model, presumably by inducing HO-1. Taken together our data showed that Sal B ameliorates liver injury in aGvHD by decreasing inflammatory responses via upregulation of HO-1. It may provide a novel way to deal with this disease.

Topics: Acute Disease; Animals; Benzofurans; Disease Models, Animal; Gene Expression Regulation, Enzymologic; Graft vs Host Disease; Heme Oxygenase-1; Inflammation; Liver; Liver Diseases; Male; Membrane Proteins; Mice; Up-Regulation

Naturally occurring antioxidants prevent or delay the harmful effect of free radical formation and radioprotection. The present study aimed to investigate the radioprotective effect of dieckol, a naturally occurring marine bioactive phenolic compound on lipid peroxidation and antioxidant status, DNA damage, and inflammation in gamma-radiation-induced rat primary hepatocytes. Isolated hepatocyte cells exposed to gamma-radiation showed an increased level of lipid peroxidation markers (thiobarbituric acid reactive substances and lipid hydroperoxides) accompanied with the decrease in the activities of enzymatic (SOD, CAT, and GPx) and non-enzymatic (vitamin C, vitamin E, and GSH) antioxidants associated with increased DNA damage coupled with upregulation of inflammatory proteins (NF-κB and COX-2) compared to control. Treatment of dieckol (5, 10, 20 μM) reduces the γ-radiation-induced toxicity and the associated pro-oxidant and antioxidant imbalance as well as decreasing the DNA damage (tail length, tail moment, %DNA in a tail and olive tail moment) and inflammation in hepatocyte cells. These findings indicate that treatment of dieckol offers protection against γ-radiation-induced cellular damage in the liver cells.

Topics: Animals; Antioxidants; Benzofurans; Cell Survival; DNA Damage; Gamma Rays; Hepatocytes; Inflammation; Lipid Peroxidation; Male; Oxidative Stress; Radiation-Protective Agents; Rats; Rats, Wistar

Moracin M, a phenolic component obtained from Mori Cortex, has been reported to have anti-inflammatory activities. The present study was designed to investigate the effects and mechanisms of Moracin M on lipopolysaccharide (LPS)-treated nucleus pulposus cells (NPCs) in intervertebral disc. NPCs were treated with moracin M at different concentrations for 1 h and then stimulated with LPS (0.5 μg/mL) for 24 h. The result demonstrated that moracin M could significantly inhibit LPS-induced inflammation. The elevated levels of IL-1β, TNF-α and IL-6 induced by LPS could be reversed by moracin M in NPCs. Moreover, moracin M increased the expressions of autophagy-related proteins and up-regulated the phosphorylation of PI3K/Akt/mTOR in LPS-treated NPCs. In conclusion, our data demonstrated that moracin M might inhibit LPS-induced PI3K and Akt phosphorylation, which leading to promote the autophagy and inhibit the inflammatory mediator production in NPCs.

Topics: Animals; Anti-Inflammatory Agents; Autophagy; Benzofurans; Cells, Cultured; Cytokines; Inflammation; Inflammation Mediators; Intervertebral Disc; Lipopolysaccharides; Morus; Nucleus Pulposus; Oncogene Protein v-akt; Phosphatidylinositol 3-Kinases; Phosphorylation; Plant Bark; Rats; Rats, Sprague-Dawley; Resorcinols; Signal Transduction; TOR Serine-Threonine Kinases

Morus bombycis Koidzumi, commonly known as silkworm mulberry, is a plant belonging to family Moraceae. It has been used in Asian countries as a traditional medicine for treating hypertension, diabetes, and inflammatory disorders. In this study, we isolated eleven compounds from the cortex of M. bombycis and evaluated their inhibitory effects on nitric oxide (NO) production as an indicator of their anti-inflammatory activities using lipopolysaccharide (LPS)-stimulated murine macrophages. Compound 4 showed the most potent inhibitory activity on NO production. It was identified as mulberrofuran K (MFK). Anti-inflammatory activity of MFK was then carried out using LPS-stimulated RAW264.7 cells. MFK suppressed the production of NO, reactive oxygen species (ROS), and proinflammatory cytokines (interleukin (IL)-1β, IL-6 and tumor necrosis factor alpha (TNF-α)) in a concentration-dependent manner. Western blot analysis revealed that MFK treatment inhibited expression levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). MFK also inhibited transcriptional activation of nuclear factor-κB (NF-κB) and extracellular-regulated kinases (ERK) 1/2 in LPS-stimulated murine macrophages. These results suggest that MFK, an anti-inflammatory constituents of M. bombycis cortex, has potential as a therapeutic candidates for preventing and treating inflammatory diseases.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Cytokines; Inflammation; Inflammation Mediators; Lipopolysaccharides; Macrophages; Medicine, East Asian Traditional; Mice; Morus; NF-kappa B; Nitric Oxide; Plant Bark; RAW 264.7 Cells; Reactive Oxygen Species

BACKGROUND Salvianolic acid B (SB) is a major active phyto-component of the plant Radix Salvia miltiorrhiza, which is traditionally used to treat joint pain and arthritis. The present study examined the anti-rheumatoid arthritis efficacy of SB on collagen-induced rheumatoid arthritis (CIA) in a rat model. MATERIAL AND METHODS Forty-eight rats were divided into 4 groups: Control rats treated with saline (Group I), rats subjected to CIA induction by intradermal injection of bovine collagen II type at the tail (Group II), and rats subjected to CIA and supplemented with either 20 or 40 mg/kg of SB for 28 days (group III or IV). RESULTS Paw swelling, edema, arthritis score, thymus and spleen indexes, and neutrophil infiltration were significantly decreased (p<0.01) by treatment with 20 or 40 mg/kg of SB. The levels of inflammatory cytokines (interleukin-1β, -6, and -17, and TNF-α) and anti-collagen II-specific immunoglobulins (IgG1 and IgG2a) were markedly decreased (p<0.01), and those of antioxidant enzymes (SOD, CAT, and GSH) were significantly increased (p<0.01) in SB-treated rats. Administration with SB (20 or 40 mg/kg) resulted in lower phosphorylated IkB-a and NF-κB p65 protein levels and markedly downregulated IκB-a expression. Furthermore, CIA rats revealed the presence of highly diffused polymorphonuclear cells (PMNs) infiltration with eroded cartilage; however, these phenomena were considerably ameliorated by SB. CONCLUSIONS SB alleviates oxidative stress and inflammation in CIA rats, thus verifying its anti-rheumatoid arthritis property.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Antirheumatic Agents; Arthritis, Experimental; Arthritis, Rheumatoid; Benzofurans; Disease Models, Animal; Down-Regulation; Edema; Inflammation; Inflammation Mediators; Male; NF-kappa B; NF-KappaB Inhibitor alpha; Oxidative Stress; Plant Extracts; Rats; Rats, Sprague-Dawley; Transcription Factor RelA

Topics: Animals; Antidepressive Agents; Anxiety; Behavior, Animal; Benzofurans; Citalopram; Depression; Depressive Disorder, Major; Eukaryotic Initiation Factor-4E; Female; Fluoxetine; Inflammation; Ketamine; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-KappaB Inhibitor alpha; Phosphorylation; Protein Biosynthesis; Protein Serine-Threonine Kinases; Serotonin and Noradrenaline Reuptake Inhibitors; Synaptic Transmission; Tumor Necrosis Factor-alpha

Doxorubicin (DOX) is a broad-spectrum antitumor drug while its use is limited due to its neurobiological side effects associated with depression. We investigated the neuroprotective efficacy of dl-3-n-butylphthalide (dl-NBP) against DOX-induced anxiety- and depression-like behaviors in rats. dl-NBP was given (30 mg/kg) daily by gavage over three weeks starting seven days before DOX administration. Elevated plus maze (EPM) test, forced swimming test (FST), and sucrose preference test (SPT) were performed to assess anxiety- and depression-like behaviors. Our study showed that the supplementation of dl-NBP significantly mitigated the behavioral changes induced by DOX. To further explore the mechanism of neuroprotection induced by dl-NBP, several biomarkers including oxidative stress markers, endoplasmic reticulum (ER) stress markers, and neuroinflammatory cytokines in the hippocampus were quantified. The results showed that dl-NBP treatment alleviated DOX-induced neural apoptosis. Meanwhile, DOX-induced oxidative stress and ER stress in the hippocampus were significantly ameliorated in dl-NBP pretreatment group. Our study found that dl-NBP alleviated the upregulation of malondialdehyde (MDA), nitric oxide (NO), CHOP, glucose-regulated protein 78 kD (GRP-78), and caspase-12 and increased the levels of reduced glutathione (GSH) and activities of catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPx) in the hippocampus of rats exposed to DOX. Additionally, the gene expression of interleukin-6 (IL-6), interleukin-1

Topics: Antibiotics, Antineoplastic; Behavioral Symptoms; Benzofurans; Doxorubicin; Endoplasmic Reticulum Stress; Humans; Inflammation; Neuroprotective Agents; Oxidative Stress

The current study was aimed to investigate the effect of benzofuran on asthma neonatal rat model. Twenty-five neonatal rats were assigned into five groups; Normal control, untreated, 1 mg/kg, 8 mg/kg and 10 mg/kg treatment groups. Methacholine was administered orally to the rats of untreated and treatment groups. Animals in the normal control group were given PBS as a vehicle. FlexiVent system employing a computer-controlled mouse ventilator along with respiratory mechanics was used for the analysis of airway resistance in the rats. Cytokine level and IFN-γ in the rat serum samples was performed by ELISA in accordance with the instructions of manufacturer. Methacholine administration into the rats caused a marked increase in lung airway resistance. However, treatment with 8 and 10 mg/kg doses of benzofuran led to marked decrease in the airway resistance. Benzofuran treatment prevented accumulation of macrophages and inflammatory cells in the lung airways. Inhibition of inflammation in methacholine administered rats by benzofuran was also confirmed by hematoxylin & eosin-staining. Examination of the rat serum showed significantly higher level of Th2 cytokines (IL-4, -5 and -13) in the untreated rats. However, treatment of methacholine administered rats with benzofuran significantly inhibited Th2 cytokine expression. The level of IFN-γ was increased by benzofuran treatment in methacholine administered rats. In methacholine administered rats the level of IgE was markedly higher however treatment of asthma rats with benzofuran inhibited up-regulation of IgE significantly. The expression of T-bet is decreased and that of GATA-3 is increased by methacholine administration in the rat lungs. Benzofuran treatment of methacholine administered rats prevented reduction in T-bet and up-regulation of GATA-3 expression in the rat lungs. The effect of benzofuran was significant at the doses of 8 and 10 mg/kg and non-significant at 1 mg/kg. These finding suggest that benzofuran inhibits expression of dominant T-helper 2 cytokines through targeting GATA-binding protein 3 transcription factor. Thus benzofuran can be of therapeutic importance for the treatment of asthma.

Topics: Animals; Anti-Asthmatic Agents; Asthma; Benzofurans; Bronchoconstrictor Agents; Cytokines; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; GATA3 Transcription Factor; Histocytochemistry; Inflammation; Lung; Methacholine Chloride; Rats; Serum; Treatment Outcome

Salvianolic acid B (SAB) is one the major phytocomponents of Radix Salvia miltiorrhiza and exhibit numerous health promoting properties. The objective of the current study was to examine whether SAB exerts a renoprotective effect by attenuating oxidative stress and inflammatory response through activating phosphatidylinositol 3-kinase/serine-threonine kinase B (PI3K/Akt) signaling pathway in a renal ischemic reperfusion rat model. Forty Sprague-Dawley male rats (250-300 g) were obtained and split into four groups with ten rats in each group. The right kidney of all rats was removed (nephrectomy). The rats of the Control group received only saline (occlusion) and served as a sham control group, whereas rats subjected to ischemic reperfusion (IR) insult by clamping the left renal artery served as a postitive control group. The other 2 groups of rats were pretreated with SAB (20 and 40 mg·kg-1·day-1) for 7 days prior IR induction and served as treatment groups (SAB 20+IR; SAB 40+IR). Renal markers creatinine (Cr) and blood urea nitrogen (BUN) were significantly lower in the groups that received SAB. Pretreatment with SAB appears to attenuate oxidative stress by suppressing the production of lipid peroxidation products like malondialdehyde as well as elevating antioxidant activity. The concentration of inflammatory markers and neutrophil infiltration (myeloperoxidase) were significantly decreased. Meanwhile, PI3K protein expression and pAkt/Akt ratio were significantly upregulated upon supplementation with SAB, indicating its renoprotective activity. Taken together, these results indicate that SAB can therapeutically alleviate oxidative stress and inflammatory process via modulating PI3K/Akt signaling pathway and probably ameliorate renal function and thus act as a renoprotective agent.

Topics: Animals; Benzofurans; Blood Urea Nitrogen; Creatinine; Drugs, Chinese Herbal; Inflammation; Kidney; Lipid Peroxidation; Male; Oxidative Stress; Peroxidase; Phosphatidylinositol 3-Kinases; Protective Agents; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction

Calpocalyx dinklagei Harms (Fabaceae) is a tropical medicinal tree, which is indigenous to Western Africa. A phytochemical study of this local plant species from its stem bark has led to the isolation of two previously undescribed aryl benzofuran derivatives, named dinklagein A and B, together with eight known compounds. Their chemical structures were elucidated by use of extensive spectroscopic methods (IR, HREI-MS and 1D and 2D NMR). Among all isolates, dinklagein A displayed remarkably potent inhibitory activity against the production of nitric oxide (NO) in the lipopolysaccharide (LPS) induced RAW264.7 macrophages. SAR and molecular docking investigations on iNOS and previously undescribed compounds (dinklagein A and B) supported experimental data. Furthermore, dinklagein A dose dependently suppressed the LPS-stimulated iNOS expression at both mRNA and protein level. It also attenuated IL-1β release, mRNA expressions of IL-1β and COX-2 at low doses. These results suggest that dinklagein A can be developed as natural, multi-target agent against several inflammatory diseases.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Cyclooxygenase 2; Fabaceae; Flavanones; Inflammation; Interleukin-1beta; Lipopolysaccharides; Macrophages; Mice; Molecular Docking Simulation; Molecular Structure; Nitric Oxide; Nitric Oxide Synthase Type II; Plant Bark; RAW 264.7 Cells; Structure-Activity Relationship

Although accumulating evidence suggests that activated microglia are associated with deficits in neurogenesis and contribute to the physiopathology of major depressive disorder, the role of microglia in treating depression remains poorly understood. Our previous study showed that salvianolic acid (SalB) has the regulation of neuroinflammatory responses and antidepressant-like effects. Here, we hypothesized that SalB's therapeutic effects occur because it modulates microglial phenotypes that are associated with neurogenesis. To test this hypothesis, we treated CMS-exposed C57BL/6 mice with SalB (20mg/kg, intraperitoneally, once daily) for 3weeks and investigated microglial phenotypic profiles and hippocampal neurogenesis. The results showed that the SalB treatment skewed M1 microglial polarization toward M2 activation in the hippocampus and cortex and remedied CMS-induced deficits in hippocampal neurogenesis. SalB (40µM) inhibited LPS-stimulated microglial M1 activation as well as induced M2 activation in vitro, and the cultured microglia with the SalB treatment showed enhanced neural precursor cell proliferation, differentiation, and survival. SalB treatment also ameliorated the depressive-like behaviors of the CMS-treated mice in sucrose preference, forced swimming, and tail suspension tests. These findings suggest a possible antidepressive mechanism for anti-inflammatory agents that is correlated with microglial polarization and hippocampal neurogenesis and which may provide a new microglia-targeted strategy for depression therapy.

Topics: Animals; Benzofurans; Cerebral Cortex; Depression; Depressive Disorder; Hippocampus; Inflammation; Inflammation Mediators; Male; Mice, Inbred C57BL; Microglia; Neurogenesis; Phenotype; Stress, Psychological

Topics: Animals; Benzofurans; Cyclooxygenase 2; Diet, High-Fat; Dietary Supplements; Humans; Inflammation; Interleukin-10; Interleukin-6; Male; Mice; Mice, Inbred C57BL; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; Plant Extracts; Salvia miltiorrhiza; Tumor Necrosis Factor-alpha

Alzheimer's Disease (AD) is one of the commonest neural degeneration in aging population, and has become a global health challenge. 2-(2-benzofuranyl)-2-imidazoline (2-BFI) was reported to effectively improved the damage of patients with neuropathological disorders. In the present study, we investigated the effect of 2-BFI on the improvement of antioxidative, inflammation, and apoptosis in AD rats. Sprague-Dawley rats (2 months old, n=40) were used in this study and after injection of Aβ1-42 into hippocampal CA1 (Cornu Ammonis) region, the rats were given high, moderate and low dose of 2-BFI though intraperitoneal (i.p.) injection. Then spatial memory and navigation ability were analyzed by Morrize Water Maze. For the molecular testing, chemical colorimetry, ELISA and immunoblotting were performed to measure the activities of antioxidative enzymes, the abundance of immune cytokines and expression of apoptotic proteins, respectively. Hematoxylin and Eosin staining was used to analyze the pathological changes. We observed that 2-BFI significantly ameliorated the learning and memory abilities in rat models with AD by dosage treatment, as demonstrated by the shorten learning latency and greater times of travel across the platform quadrant. Additionally, reactive oxygen species (ROS) and malondialdehyde (MDA), were decreased after treatment of 2-BFI with dosage dependency, while the activities of superoxidase dismutase (SOD) and (GPX) Glutathione peroxidase were in turn enhanced, suggesting that 2-BFI could protect the antioxidative enzymes and reduce the oxidative stress in the hippocampus. Moreover, the expression of inflammatory factors including TNF-a and IL-1β were decreased after 2-BFI treatment. Additionally, the neuronal apoptosis was also attenuated, as shown by Western blot results. Taken together, the cognitive impairment in AD rats could be significantly improved by 2-BFI in a dose-dependent manner through suppressing oxidants accumulation, inhibiting of inflammatory response, as well as enhancing the neural viability.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Benzofurans; Disease Models, Animal; Dose-Response Relationship, Drug; Hippocampus; Imidazoles; Inflammation; Maze Learning; Neuroprotective Agents; Nootropic Agents; Oxidative Stress; Peptide Fragments; Random Allocation; Rats, Sprague-Dawley; Spatial Memory; Spatial Navigation

Cyclic GMP-AMP synthase is essential for innate immunity against infection and cellular damage, serving as a sensor of DNA from pathogens or mislocalized self-DNA. Upon binding double-stranded DNA, cyclic GMP-AMP synthase synthesizes a cyclic dinucleotide that initiates an inflammatory cellular response. Mouse studies that recapitulate causative mutations in the autoimmune disease Aicardi-Goutières syndrome demonstrate that ablating the cyclic GMP-AMP synthase gene abolishes the deleterious phenotype. Here, we report the discovery of a class of cyclic GMP-AMP synthase inhibitors identified by a high-throughput screen. These compounds possess defined structure-activity relationships and we present crystal structures of cyclic GMP-AMP synthase, double-stranded DNA, and inhibitors within the enzymatic active site. We find that a chemically improved member, RU.521, is active and selective in cellular assays of cyclic GMP-AMP synthase-mediated signaling and reduces constitutive expression of interferon in macrophages from a mouse model of Aicardi-Goutières syndrome. RU.521 will be useful toward understanding the biological roles of cyclic GMP-AMP synthase and can serve as a molecular scaffold for development of future autoimmune therapies.Upon DNA binding cyclic GMP-AMP synthase (cGAS) produces a cyclic dinucleotide, which leads to the upregulation of inflammatory genes. Here the authors develop small molecule cGAS inhibitors, functionally characterize them and present the inhibitor and DNA bound cGAS crystal structures, which will facilitate drug development.

Topics: Animals; Autoimmune Diseases; Autoimmune Diseases of the Nervous System; Autoimmunity; Benzofurans; DNA; Enzyme Inhibitors; High-Throughput Screening Assays; Immunity, Innate; Inflammation; Macrophages; Mass Spectrometry; Mice; Nervous System Malformations; Nucleotidyltransferases; Small Molecule Libraries; Structure-Activity Relationship

The NLRP3 inflammasome activation and neuroinflammation are known to be involved in the pathology of depression, whereas autophagy has multiple effects on immunity, which is partly mediated by the regulation of inflammasome and clearance of proinflammatory cytokines. Given the emerging evidence that autophagy dysfunction plays an essential role in depression, it is very likely that autophagy may interact with the inflammatory process in the development and treatment of depression. Salvianolic acid B (SalB), a naturally occurring compound extracted from Salvia miltiorrhiza, contains anti-inflammatory and antidepression properties and has recently been proven to modulate autophagy. In this study, we sought to investigate whether autophagy is involved in the inflammation-induced depression and the antidepressant effects of SalB.. The effects of prolonged lipopolysaccharide (LPS) treatment and SalB administration on behavioral changes, neuroinflammation, autophagic markers and NLRP3 activation in rat hippocampus were determined by using behavioral tests, real-time PCR analysis, western blot, and immunostaining.. Our data showed that periphery immune challenge by LPS for 2 weeks successfully induced the rats to a depression-like state, accompanied with enhanced expression of pro-inflammatory cytokines and NLRP3 inflammasome activation. Interestingly, autophagic markers, including Beclin-1, and the ratio of LC3II to LC3I were suppressed following prolonged LPS exposure. Meanwhile, co-treatment with SalB showed robust antidepressant effects and ameliorated the LPS-induced neuroinflammation. Additionally, SalB restored the compromised autophagy and overactivated NLRP3 inflammasome in LPS-treated rats.. Collectively, these data suggest that autophagy may interact with NLRP3 activation to contribute to the development of depression, whereas SalB can promote autophagy and induce the clearance of NLRP3, thereby resulting in neuroprotective and antidepressant actions.

Topics: Animals; Anti-Inflammatory Agents; Autophagy; Behavior, Animal; Benzofurans; Depression; Inflammasomes; Inflammation; Lipopolysaccharides; Male; NLR Family, Pyrin Domain-Containing 3 Protein; Rats; Rats, Sprague-Dawley

Suppressing cytokine responses has frequently been shown to have promising therapeutic effects for many chronic inflammatory and autoimmune diseases. However, the severe side effects associated with the long-term use of current treatments, such as allergic reactions and increased risk of stroke, have focused attention towards the targeting of intracellular signaling mechanisms, such as NF-κB, that regulate inflammation. We synthesized a series of non-natural aurone derivatives and investigated their ability to suppress pro-inflammatory signaling in human monocyte (THP-1) and murine macrophage-like (RAW 267.4) cell lines. One of these derivatives, (Z)-2-((5-(hydroxymethyl) furan-2-yl) methylene) benzofuran-3(2H)-one (aurone 1), was found to inhibit LPS-induced secretion of the pro-inflammatory cytokines, tumor-necrosis factor α (TNFα), interleukin 1β (IL-1β), and IL-8 by THP-1 cells. To investigate the mechanism, we probed the effect of aurone 1 on LPS-induced MAPK and NF-κB signaling in both THP-1 and RAW264.7. While aurone 1 pre-treatment had no effect on the phosphorylation of ERK, JNK, or p38 MAPK, it strongly suppressed activation of IKK-β, as indicated by attenuation of Ser176/180 phosphorylation, resulting in decreased phosphorylation of p65 (ser536) as well as phosphorylation (ser32) and degradation of IκBα. Consistent with this, aurone 1 significantly reduced LPS-stimulated nuclear translocation of p65-containing NF-κB transcription factors and expression of an mCherry reporter of TNFα gene transactivation in RAW264.7 cells. Inhibition of TNFα expression at the transcription level was also demonstrated in THP-1 by qRT-PCR. In addition to its effects on cytokine expression, aurone 1 pre-treatment decreased expression of iNOS, a bona fide NF-κB target gene and marker of macrophage M1 polarization, resulting in decreased NO production in RAW264.7 cells. Together, these data indicate that aurone 1 may have the potential to function as a pharmacological agent for the treatment of chronic inflammation disorders.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Cytokines; Humans; Inflammation; Inflammation Mediators; Lipopolysaccharides; Macrophages; Mice; Monocytes; NF-kappa B; Nitric Oxide Synthase Type II; RAW 264.7 Cells; Signal Transduction; Tumor Necrosis Factor-alpha

Neuroinflammation plays a critical role in the pathogenesis of ischemia/reperfusion (I/R) injury. Activated platelets are increasingly regarded as initiators and/or amplifiers of inflammatory processes in cerebral I/R injury. Salvianolic acid B (SAB) is the most abundant bioactive compound of Salviae miltiorrhizae, a well-known Chinese herb used to promote blood circulation and eliminating blood stasis. S. miltiorrhizae has been used clinically in Asia for the treatment of ischemic cerebrovascular diseases. In the present study, a rat model of transient middle cerebral artery occlusion (tMCAO) was established to investigate the neuroprotective effects and mechanisms of SAB treatment against focal cerebral I/R insult. The results showed that SAB treatment (3mg/kg, 6mg/kg and 12mg/kg, i.p.) dose-dependently decreased I/R-induced neurological deficits at 24, 48, and 72h after reperfusion and decreased plasma-soluble P-selectin and soluble CD40 ligand as early as 6h after onset of I/R insult. At 24h after reperfusion, SAB treatment significantly reduced neuronal and DNA damage in the hippocampal CA1 region and decreased neural cell loss in the ischemic core. The I/R-induced pro-inflammatory mediator mRNA and protein overexpression in the penumbra cortex, including ICAM-1, IL-1β, IL-6, IL-8, and MCP-1, were significantly inhibited by SAB in a dose-dependent manner. Further studies suggested SAB treatment attenuated CD40 expression and NF-κB activation, which involved NF-κB/p65 phosphorylation and IκBα phosphorylation and degradation. In conclusion, our findings indicated that the neuroprotective effects of SAB post cerebral I/R injury are associated with the inhibition of both platelets activation and production of pro-inflammatory mediators and the downregulation of the CD40/NF-κB pathway.

Topics: Animals; Benzofurans; Blood Platelets; Brain Ischemia; CA1 Region, Hippocampal; CD40 Antigens; Dose-Response Relationship, Drug; Infarction, Middle Cerebral Artery; Inflammation; Male; Neuroimmunomodulation; Neuroprotective Agents; NF-kappa B; Platelet Activation; Rats; Rats, Wistar; Reperfusion; Reperfusion Injury; Signal Transduction; Transcription Factor RelA

Osteoarthritis (OA) is a chronic progressive disease that has complicated mechanisms that involve inflammation and cartilage degradation. In this study, we investigated the anti-inflammatory action of Salvianolic acid B (Sal B) in both human OA chondrocytes and a mouse OA model that was induced by destabilization of the medial meniscus. In vitro, chondrocytes were pretreated with Sal B (0, 25, 50, 100μM) for 2h, then incubated with IL-1β (10ng/mL) for 24h. NO production was determined by Griess method and PGE2 was assessed by ELISA. The expression of INOS, COX-2, MMP-13, ADAMTS-5 and NF-κB-related signaling molecules were tested by Western blotting. Immunofluorescence staining was used to detect P65 nuclear translocation. In vivo, the mouse OA model received intraperitoneal-injection of either Sal B (25mg/kg) or saline every other day. Hematoxylin and Eosin, as well as Safranin-O-Fast green staining, were utilized to evaluate the severity of cartilage lesions up to 8weeks following the surgery. Sal B inhibited the over-production of NO and PGE2, while the elevated expression of INOS, COX-2, MMP-13 and ADAMTS-5 were reversed by Sal B in IL-1β-induced chondrocytes. In addition, IL-1β significantly induced phosphorylation of NF-κB signaling, and this phosphorylation response was blocked by Sal B. Immunofluorescence staining demonstrated that Sal B could suppress IL-1β-induced p65 nuclear translocation. In vivo, the cartilage in Sal B-treated mice exhibited less cartilage degradation and lower OARSI scores. Taken together, Sal B possesses great potential value as a therapeutic agent for OA treatment.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Cartilage; Chondrocytes; Cytokines; Disease Models, Animal; Humans; Inflammation; Interleukin-1beta; Male; Matrix Metalloproteinase 13; Menisci, Tibial; Mice; Mice, Inbred C57BL; NF-kappa B; Nitric Oxide; Osteoarthritis; Phosphorylation; Signal Transduction

The effects of licocoumarone (LC) isolated from Glycyrrhiza uralensis were studied in LPS-stimulated RAW 264.7 macrophages. Our study demonstrated that LC dose-dependently attenuated LPS-induced NO production by down-regulating iNOS expression. Additionally, the treatment with LC inhibited LPS-induced expression of cytokines including IL-1β, IL-6 and IL-10, but not TNF-α, at both mRNA and protein levels. Similar suppressive effects of LC were observed on LPS-stimulated murine peritoneal macrophages as well. Furthermore, LC significantly reduced LPS-stimulated NF-κB activation by inhibition of IκBα degradation and p65 phosphorylation. The results from NF-κB-luc reporter gene assay further support the inhibitory effect of LC on NF-κB activation. Further studies showed that LC also interfered with the MAPKs and STAT3 signaling pathways, which are typical inflammatory signaling pathways triggered by LPS. Taken together, these results show that LC attenuates LPS-induced cytokine gene expression in RAW 264.7 macrophages through mechanisms that involve NF-κB, MAPKs and STAT3 signaling pathways, but the pattern of inhibition differs from that of a global immunosuppresant. Our study indicates that LC is a functional constituent of Glycyrrhiza uralensis with potential implications in infectious and immune-related diseases.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Cell Survival; Drug Evaluation, Preclinical; Gene Expression Regulation, Enzymologic; Glycyrrhiza uralensis; Inflammation; Interleukin-10; Interleukin-1beta; Interleukin-6; Lipopolysaccharides; Macrophages; MAP Kinase Signaling System; Mice; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; RAW 264.7 Cells; Resorcinols; RNA, Messenger; STAT3 Transcription Factor; Tumor Necrosis Factor-alpha

Microglia activation-induced neuroinflammation contributes to neuronal damage in neurodegenerative diseases. Inhibition of microglia activation and reduction of major neurotoxic cytokines have been becoming a therapeutic strategy for neurodegenerative diseases. L-3-n-Butylphthalide (L-NBP) has shown the potent neuroprotective effects in stroke and Alzheimer's disease animal models. The present study investigated the immune modulatory effects of L-NBP on pro-inflammatory cytokines and microglia activation in brain tissue induced by systemic lipopolysaccharide (LPS) treatment in C57BL/6 mice. Our results showed that systemic LPS treatment induced microglia activation in the brain. L-NBP treatment significantly suppressed the expression of proinflammatory cytokines, such as tumor necrosis factor (TNFα), interlukin-1β (IL-1β), interlukin-6 (IL-6), and interlukin-10 (IL-10) in LPS-treated mice. At the meantime, L-NBP treatment decreased the morphological activation of microglia. In addition, the phosphorylation level of JNK MAP kinase-signaling pathway was also inhibited by L-NBP in LPS-treated mice. Furthermore, L-NBP upregulated the expression of heme oxygenase (HO)-1, a key element in the anti-inflammation and anti-oxidative stress. These results suggested that L-NBP might be a promising candidate in delaying and reversing the progress of neurodegenerative diseases by inhibiting microglia activation.

Topics: Animals; Benzofurans; Brain; Cytokines; Disease Models, Animal; Heme Oxygenase-1; Immunologic Factors; Inflammation; Lipopolysaccharides; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Microglia; Mitogen-Activated Protein Kinases; Molecular Structure; Neuroprotective Agents; Phosphorylation; Signal Transduction; Tumor Necrosis Factor-alpha; Up-Regulation

Topics: Benzofurans; Enteric Nervous System; Inflammation; Neurons; Neuroprotective Agents; Oxidative Stress; Receptors, Serotonin, 5-HT4; Serotonin 5-HT4 Receptor Agonists

The therapeutic effectiveness of moracins as 2-arylbenzofuran derivatives against airway inflammation was examined. Moracin M, O, and R were isolated from the root barks of Morus alba, and they inhibited interleukin (IL)-6 production from IL-1β-treated lung epithelial cells (A549) at 101-00μM. Among them, moracin M showed the strongest inhibitory effect (IC50=8.1μM). Downregulation of IL-6 expression by moracin M was mediated by interrupting the c-Jun N-terminal kinase (JNK)/c-Jun pathway. Moracin derivatives inhibited inducible nitric oxide synthase (iNOS)-catalyzed NO production from lipopolysaccharide (LPS)-treated alveolar macrophages (MH-S) at 50-100μM. In particular, moracin M inhibited NO production by downregulating iNOS. When orally administered, moracin M (20-60mg/kg) showed comparable inhibitory action with dexamethasone (30mg/kg) against LPS-induced lung inflammation, acute lung injury, in mice with that of dexamethasone (30mg/kg). The action mechanism included interfering with the activation of nuclear transcription factor-κB in inflamed lungs. Therefore, it is concluded that moracin M inhibited airway inflammation in vitro and in vivo, and it has therapeutic potential for treating lung inflammatory disorders.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Biocatalysis; Cell Line, Tumor; Humans; Inflammation; Interleukin-1beta; Interleukin-6; JNK Mitogen-Activated Protein Kinases; Lung; Male; Mice; NF-kappa B; Nitric Oxide; Nitric Oxide Synthase Type II; Resorcinols; Signal Transduction

Artocarpus heterophyllus, a popular tropical fruit commonly known as the jackfruit tree, is normally planted in subtropical or tropical areas. Since a variety of phytochemicals isolated from A. heterophyllus have been found to possess potently anti-inflammatory, antiviral and antimalarial activities, researchers have devoted much interest to its potential pharmaceutical value. However, the exact mechanism underlying its anti-inflammatory activity is not well characterized. In this study, seven natural products isolated from A. heterophyllus, including 25-Hydroxycycloart-23-en-3-one (HY), Artocarpin (AR), Dadahol A (DA), Morachalcone A (MA), Artoheterophyllin B (AB), Cycloheterophyllin (CY) and Moracin C (MC) were collected. Lipopolysaccharide (LPS)-stimulated inflammatory response in RAW264.7 macrophages were used in this study. Among these compounds, MC significantly inhibited LPS-activated reactive oxygen species (ROS) and nitric oxide (NO) release without marked cytotoxicity. Furthermore, MC effectively reduced LPS stimulated up-regulation of mRNA and protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and serval pro-inflammatory cytokines (interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α)). Mechanistic studies revealed that the anti-inflammatory effect of MC was associated with the activation of the mitogen activated protein kinases (MAPKs) (including p38, ERK and JNK) and nuclear factor-κB (NF-κB) pathways, especially reducing the nuclear translocation of NF-κB p65 subunit as revealed by nuclear separation experiment and confocal microscopy.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Artocarpus; Benzofurans; Blotting, Western; Cell Proliferation; Cells, Cultured; Cytokines; Fluorescent Antibody Technique; HEK293 Cells; Humans; Inflammation; Lipopolysaccharides; Macrophages; Mice; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Stilbenes

N-Butylphthalide (NBP) has been known to have potential neuroprotective effects in Alzheimer's disease and stroke animal models. Hepatocyte-growth factor (HGF), with strong angiogenic properties, exerted protective role in brain injury. The present study was aimed to investigate the possible anti-inflammatory effects of NBP on the brain injury of rats with cerebral ischemia reperfusion (IR) and astrocytes activation induced by lipopolysaccharide (LPS) treatment. Our results showed that cerebral IR induced brain damage with down-regulation of HGF and astrocytes activation. NBP treatment significantly increased HGF expression and activated cMet/PI3K/AKT signaling pathway, stimulating mTOR activity and suppressing apoptosis in brain tissues. Also NBP inhibited pro-inflammatory cytokines expression, including IL-6, IL-1β, and TNFα, via TLR4/NF-κB suppression. Anti-HGF treatment enhanced TLR4 expression while HGF could suppress TLR4 activation and its down-streaming signals, attenuating inflammation finally. Notably, NBP up-regulated HGF and down-regulated TLR4 expression significantly in the astrocytes combined with the treatment of TLR4 inhibitor than the cells only treated with TLR4 inhibitor, suggesting that NBP could further suppress TLR4 activation, suggesting that NBP might impede TLR4 through up-regulating HGF expression. These results suggested that NBP treatment significantly ameliorated cerebral IR-induced brain injury by inhibiting TLR4/NF-κB-associated inflammation regulated by HGF.

Topics: Animals; Astrocytes; Benzofurans; Brain Ischemia; Cell Survival; Hepatocyte Growth Factor; Humans; Inflammation; Lipopolysaccharides; Male; NF-kappa B; Rats, Sprague-Dawley; Reperfusion Injury; Signal Transduction; Toll-Like Receptor 4; Up-Regulation

Salvianolic acid B (SAB) is a hydrophilic component isolated from the Chinese herb Salviae miltiorrhizae, which has been used clinically for the treatment of ischemic cardiovascular and cerebrovascular diseases. Platelets-mediated vascular inflammatory response contributes to the initiation and progression of atherosclerosis. In this paper, we focus on the modulating effects of SAB on the inflammatory reaction of endothelial cells triggered by activated platelets. Human umbilical vein endothelial cells (EA.hy926) were pretreated with SAB followed by co-culture with ADP-activated platelets. Adhesion of platelets to endothelial cells was observed by amorphological method. The activation of nuclear factor-kappa B was evaluated by NF-κB p65 nuclear translocation and the protein phosphorylation. A determination of the pro-inflammatory mediators (ICAM-1, IL-1β, IL-6, IL-8, MCP-1) mRNA and protein were also conducted. In addition, the inhibitory effects of SAB on platelets activation were also evaluated using a platelet aggregation assay and assessing the release level of soluble P-selectin. The results showed that SAB dose-dependently inhibited ADP- or α-thrombin-induced human platelets aggregation in platelet rich plasma (PRP) samples, and significantly decreased soluble P-selectin release from both agonists stimulated washed platelets. It was also found that pre-treatment with SAB reduced adhesion of ADP-activated platelets to EA.hy926 cells and inhibited NF-κB activation. In addition, SAB significantly suppressed pro-inflammatory mediators mRNA and protein in EA.hy926 cells in a dose-dependent manner. These results indicated that, in addition to its inhibitory effects on platelets activation, SAB was able to attenuate platelets-mediated inflammatory responses in endothelial cells even if the platelets had already been activated. This anti-inflammatory effect was related to the inhibition of NF-κB activation. Our findings suggest that SAB may be a potential candidate for the treatment of various atherosclerotic diseases.

Topics: Benzofurans; Blood Platelets; Cell Adhesion; Cells, Cultured; Coculture Techniques; Disease Progression; Drugs, Chinese Herbal; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Human Umbilical Vein Endothelial Cells; Humans; Inflammation; Microscopy, Fluorescence; NF-kappa B; P-Selectin; Plant Preparations; Platelet Aggregation; RNA; Salvia

This study evaluated the potential anti-inflammatory effects of natural phthalides, isolated from Ligusticum porteri, and of semi-synthetic phthalides. Anti-inflammatory activity was investigated in two mouse models; one with ear edema, induced with 12-O-tetradecanoylphorbol-13-acetate, and the other with paw edema, induced with carrageenan. The effect on the RAW 264.7 stimulated with lipopolysaccharide cells was evaluated and after application of 12-O-tetradecanoylphorbol-13-acetate, the activity of myeloperoxidase was assessed to serve as an index of leukocytes infiltration together with the histological evaluations. We also assessed the inhibition of cyclooxygenases 1 and 2 in vitro. Our results demonstrated that administration of semi-synthetic phthalides significantly inhibited the ear edema induced by 12-O-tetradecanoylphorbol-13-acetate, and reduced the paw edema caused by carrageenan. The anti-inflammatory activity of phthalides could, in part, be explained by the reduction in myeloperoxidase activity and the infiltration of leukocytes. The semi-synthetic phthalides also inhibited the production of oxide nitric in RAW cells.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Biological Products; Carrageenan; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Edema; Inflammation; Male; Mice; Nitric Oxide Synthase; Nitrites; Peroxidase; RAW 264.7 Cells; Skin; Tetradecanoylphorbol Acetate

Silent information regulator 1 (SIRT1), a histone deacetylase, has been suggested to be effective in ischemic brain diseases. Salvianolic acid B (SalB) is a polyphenolic and one of the active components of Salvia miltiorrhiza Bunge. Previous studies suggested that SalB is protective against ischemic stroke. However, the role of SIRT1 in the protective effect of SalB against cerebral ischemia has not been explored. In this study, the rat brain was subjected to middle cerebral artery occlusion (MCAO). Before this surgery, rats were intraperitoneally administrated SalB with or without EX527, a specific SIRT1 inhibitor. The infarct volume, neurological score and brain water content were assessed. In addition, levels of TNF-α and IL-1β in the brain tissues were detected by commercial ELISA kits. And the expression levels of SIRT, Ac-FOXO1, Bcl-2 and Bax were detected by Western blot. The results suggested that SalB exerted a cerebral-protective effect, as shown by reduced infarct volume, lowered brain edema and increased neurological scores. SalB also exerted anti-inflammatory effects as indicated by the decreased TNF-α and IL-1β levels in the brain tissue. Moreover, SalB upregulated the expression of SIRT1 and Bcl-2 and downregulated the expression of Ac-FOXO1 and Bax. These effects of SalB were abolished by EX527 treatment. In summary, our results demonstrate that SalB treatment attenuates brain injury induced by ischemic stoke via reducing apoptosis and inflammation through the activation of SIRT1 signaling.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Benzofurans; Brain; Brain Edema; Brain Ischemia; Carbazoles; Central Nervous System Agents; Disease Models, Animal; Infarction, Middle Cerebral Artery; Inflammation; Male; Neuroprotective Agents; Random Allocation; Rats, Sprague-Dawley; Severity of Illness Index; Sirtuin 1; Stroke; Treatment Outcome

Parkinson's disease is the second most common neurodegenerative disorders after Alzheimer's disease. The main cause of the disease is the massive degeneration of dopaminergic neurons in the substantia nigra. Neuronal apoptosis and neuroinflammation are thought to be the key contributors to the neuronal degeneration.. Both CATH.a cells and ICR mice were treated with 1-methyl-4-phenylpyridin (MPP(+)) to induce neurotoxicity in vitro and in vivo. Western blotting and immunohistochemistry were also used to analyse neurotoxicity, neuroinflammation and aberrant neurogenesis in vivo. The experiment in CATH.a cells showed that the treatment of MPP(+) impaired intake of cell membrane and activated caspase system, suggesting that the neurotoxic mechanisms of MPP(+) might include both necrosis and apoptosis. Pretreatment of lithospermic acid might prevent these toxicities. Lithospermic acid possesses specific inhibitory effect on caspase 3. In mitochondria, MPP(+) caused mitochondrial depolarization and induced endoplasmic reticulum stress via increasing expression of chaperone protein, GRP-78. All the effects mentioned above were reduced by lithospermic acid. In animal model, the immunohistochemistry of mice brain sections revealed that MPP(+) decreased the amount of dopaminergic neurons, enhanced microglia activation, promoted astrogliosis in both substantia nigra and hippocampus, and MPP(+) provoked the aberrant neurogenesis in hippocampus. Lithospermic acid significantly attenuates all of these effects induced by MPP(+).. Lithospermic acid is a potential candidate drug for the novel therapeutic intervention on Parkinson's disease.

Topics: 1-Methyl-4-phenylpyridinium; Animals; Anti-Inflammatory Agents; Apoptosis; Benzofurans; Cell Line; Depsides; Inflammation; Male; Mice; Mice, Inbred ICR; Neurogenesis; Neurons

Emerging preclinical evidence suggests that imidazoline I2 receptor ligands may be effective analgesics. Quantitative analysis of the combined I2 receptor ligands and opioids is needed for the justification of combination therapy.. This study systematically examined the anti-hyperalgesic and response rate-suppressing effects of selective I2 receptor ligands (2-BFI and phenyzoline) alone and in combination with oxycodone in rats.. Von Frey filament test was used to examine the anti-hyperalgesic effects of drugs in a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain. Schedule-controlled responding was used to assess the rate-altering effects of study drugs. Duration of actions of individual drugs (2-BFI, phenyzoline, and oxycodone) alone or in combination was studied. Dose-addition analysis was employed to assess the anti-hyperalgesic interactions between drugs.. Oxycodone (0.1-3.2 mg/kg, i.p.), 2-BFI (1-17.8 mg/kg, i.p.), and phenyzoline (17.8-56 mg/kg, i.p.) all dose-dependently produced significant antinociceptive effects. When studied as combinations, 2-BFI and oxycodone produced additive interactions while phenyzoline and oxycodone produced supra-additive interactions under all fixed ratios. The same drug combinations did not alter or significantly reduced the operant responding depending on the ratios of the drug combinations.. Quantitative analysis of the anti-hyperalgesic effects of I2 receptor ligands strongly supports the therapeutic potential of I2 receptor ligands against inflammatory pain. In addition, the data reveal that phenyzoline is superior to the prototypic I2 receptor ligand 2-BFI for the management of pain and warrants further consideration as a novel analgesic.

Topics: Analgesics, Opioid; Animals; Behavior, Animal; Benzofurans; Disease Models, Animal; Drug Synergism; Hyperalgesia; Imidazoles; Imidazoline Receptors; Imidazolines; Inflammation; Ligands; Male; Nociception; Oxycodone; Pain; Protein Binding; Rats; Rats, Sprague-Dawley

A novel series of clioquinol-moracin hybrids were designed and synthesized by fusing the pharmacophores of clioquinol and moracin M, and their activities as multitarget-directed ligands against Alzheimer's disease were evaluated. Biological activity results demonstrated that these hybrids possessed significant inhibitory activities against phosphodiesterase 4D (PDE4D) and Aβ aggregation as well as remarkable antioxidant effects and excellent blood-brain barrier permeability. The optimal compound, 18d (WBQ5187), exhibited excellent PDE4D inhibitory potency (IC50 = 0.32 μM), significant antioxidant effects, appropriate biometal chelating functions, and interesting properties that modulated self- and metal-induced Aβ aggregation. Two-dimensional NMR studies revealed that 18d had significant interactions with Aβ1-42 at the R5, H6, H14, Q15, and F20 residues. Furthermore, this typical hybrid possessed preeminent neuroprotective effects against inflammation in microglial cells. Most importantly, oral administration of 18d·HCl demonstrated marked improvements in cognitive and spatial memory in a rat model of Alzheimer's disease and protected hippocampal neurons from necrosis.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Antioxidants; Benzofurans; Clioquinol; Cognition; Cyclic Nucleotide Phosphodiesterases, Type 4; Inflammation; Ligands; Male; Memory; Models, Molecular; Neurons; Neuroprotective Agents; Phosphodiesterase 4 Inhibitors; Protein Aggregates; Rats; Rats, Wistar; Resorcinols

Eisenia bicyclis is edible brown algae recognized as a rich source of bioactive derivatives mainly phlorotannins reported for their anti-oxidant properties. Of all phlorotannins identified so far, dieckol has shown the most potent effect in anti-inflammatory, radical scavenging and neuroprotective functions. However, whether dieckol up-regulates hemeoxygenase 1 (HO-1) and this mediates its anti-inflammatory effect in murine macrophages remains poorly understood. Dieckol (12.5-50 μM) inhibited nitric oxide production and attenuated inducible nitric oxide synthase, phospho (p)-PI-3K, p-Akt, p-IKK-α/β, p-IκB-α and nuclear p-NF-κBp65 protein expressions, and NF-κB transcriptional activity in LPS (0.1 μg/ml) stimulated murine macrophages. On the other hand, dieckol up-regulated HO-1 which partly mediated its anti-inflammatory effect in murine macrophages. Thus, dieckol appeared to be a potential therapeutic agent against inflammation through HO-1 up-regulation.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Benzofurans; Cell Line; Heme Oxygenase-1; Inflammation; Lipopolysaccharides; Macrophage Activation; Macrophages; Mice; NF-kappa B; Nitric Oxide; Oncogene Protein v-akt; Phaeophyceae; Phosphatidylinositol 3-Kinases; Signal Transduction; Up-Regulation

Four new ligustilides chuanxiongnolide R1 (1), chuanxiongnolide R2 (2), chuanxiongdiolide R1 (3) and chuanxiongdiolide R2 (4) together with eight known derivatives (5-12) were isolated from the root of Ligusticum chuanxiong Hort. Their structures were elucidated by HR-ESI-MS, UV, IR, 1D and 2D NMR (HSQC, HMBC, (1)H-(1)H COSY, NOESY) methods. The absolute configurations were confirmed via the circular dichroism (CD) spectrum. The anti-inflammatory assay in LPS-triggered RAW 264.7 macrophages was carried out on the twelve compounds. 1, 3, 5 and 6 showed significant inhibitory effects against LPS-induced NO production.

Topics: 4-Butyrolactone; Animals; Anti-Inflammatory Agents; Benzofurans; Drugs, Chinese Herbal; Inflammation; Ligusticum; Lipopolysaccharides; Macrophages; Mice; Molecular Structure; Nitric Oxide; Phytotherapy; Plant Roots

Muscarinic acetylcholine receptors (mAChRs) are major regulators of gut epithelial functions. However, the precise subtype composition has not been clarified.. We characterized the pharmacological profile of mAChRs on mouse colonic crypts, employing [(3)H]-N-methyl scopolamine chloride as a radioligand and several subtype-selective chemicals, and the functional aspect by measuring short-circuit current (I sc) in Ussing chambers and by evaluating MAP kinase phosphorylation in mouse colonic mucosal sheets.. The mAChRs were detected on the crypts (K d = 163.2 ± 32.3 pM, B max = 47.3 ± 2.6 fmol/mg of total cell protein). Muscarinic toxin 7 (MT-7, M1 subtype selective) gave a displacement curve with high affinity, but there was a part insensitive to MT-7 (18.8 ± 0.4 % of the total specific binding). The MT-7-insensitive component was displaced completely by darifenacin (M3 selective) with high affinity. ACh induced an increase in I sc, which was significantly enhanced by MT-7 but was completely inhibited by darifenacin or atropine. Colitis induction resulted in a significant decrease in the density of mAChRs, which occurred mainly in the MT-7-sensitive component (M1 subtype). Immunological experiments exhibited a reduction of M1 but not of M3 signal after colitis induction. Muscarinic stimulation induced an increase in MAP kinase phosphorylation, which was completely suppressed by MT-7 and was attenuated by inflammation, in mouse colonic epithelium.. These results suggest that mAChRs in mouse colonic epithelial cells consist of two subtypes, M1 (80 %) and M3 (20 %). The major M1 subtype was likely to regulate epithelial chloride secretion negatively and was susceptible to inflammation and may be relevant to inflammatory gut dysfunction.

Topics: Animals; Atropine; Benzofurans; Colitis; Colon; Elapid Venoms; Epithelial Cells; Inflammation; Intestinal Mucosa; Male; Mice; Mice, Inbred BALB C; N-Methylscopolamine; Parasympatholytics; Pyrrolidines; Radioligand Assay; Receptor, Muscarinic M1; Receptor, Muscarinic M3

Despite the excellent anti-inflammatory and immunosuppressive action of glucocorticoids (GCs), their use for the treatment of inflammatory bowel disease (IBD) still carries significant risks in terms of frequently occurring severe side effects, such as the impairment of intestinal tissue repair. The recently-introduced selective glucocorticoid receptor (GR) agonists (SEGRAs) offer anti-inflammatory action comparable to that of common GCs, but with a reduced side effect profile.. The in vitro effects of the non-steroidal SEGRAs Compound A (CpdA) and ZK216348, were investigated in intestinal epithelial cells and compared to those of Dexamethasone (Dex). GR translocation was shown by immunfluorescence and Western blot analysis. Trans-repressive effects were studied by means of NF-κB/p65 activity and IL-8 levels, trans-activation potency by reporter gene assay. Flow cytometry was used to assess apoptosis of cells exposed to SEGRAs. The effects on IEC-6 and HaCaT cell restitution were determined using an in vitro wound healing model, cell proliferation by BrdU assay. In addition, influences on the TGF-β- or EGF/ERK1/2/MAPK-pathway were evaluated by reporter gene assay, Western blot and qPCR analysis.. Dex, CpdA and ZK216348 were found to be functional GR agonists. In terms of trans-repression, CpdA and ZK216348 effectively inhibited NF-κB activity and IL-8 secretion, but showed less trans-activation potency. Furthermore, unlike SEGRAs, Dex caused a dose-dependent inhibition of cell restitution with no effect on cell proliferation. These differences in epithelial restitution were TGF-β-independent but Dex inhibited the EGF/ERK1/2/MAPK-pathway important for intestinal epithelial wound healing by induction of MKP-1 and Annexin-1 which was not affected by CpdA or ZK216348.. Collectively, our results indicate that, while their anti-inflammatory activity is comparable to Dex, SEGRAs show fewer side effects with respect to wound healing. The fact that SEGRAs did not have a similar effect on cell restitution might be due to a different modulation of EGF/ERK1/2 MAPK signalling.

Topics: Active Transport, Cell Nucleus; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Benzofurans; Benzoxazines; Cell Line; Cell Nucleus; Cell Proliferation; Epidermal Growth Factor; Gene Silencing; Humans; Inflammation; Intestinal Mucosa; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Receptors, Glucocorticoid; Transcription, Genetic; Transcriptional Activation; Transforming Growth Factor beta; Wound Healing

The phlorotannins (phloroglucinol, eckol, and dieckol) are active compounds found in Eisenia bicyclis, and have been widely investigated for their antioxidant, anti-tumor, and anti-cancer activities. In this study, we investigated the protective effects of these phlorotannins against pro-inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice treated by high mobility group box 1 protein (HMGB1), and the signaling pathways involved. The protective activities of the phlorotannins were determined by measuring permeability, leukocyte adhesion and migration, and the activations of pro-inflammatory proteins in HMGB1-activated HUVECs. We found that the phlorotannins inhibited; lipopolysaccharide (LPS)-induced HMGB1 release, HMGB1-mediated barrier disruption, the expressions of cell adhesion molecules (CAMs), and the adhesion/transendothelial migration of leukocytes to human endothelial cells. The phlorotannins also suppressed acetic acid induced-hyperpermeability and carboxymethylcellulose-induced leukocytes migration in vivo. Further studies revealed that the hydroxyl groups on dieckol positively regulated these vascular barrier protective effects. Collectively, these results suggest that phloroglucinol, eckol, and dieckol protect vascular barrier integrity by inhibiting hyperpermeability, the expressions of CAMs, and the adhesion and migration of leukocytes, which confirms their potential usefulnesses for the treatment of vascular inflammatory diseases.

Topics: Animals; Benzofurans; Blood Vessels; Blotting, Western; Cell Adhesion Molecules; Cell Membrane Permeability; Cell Movement; Cell Survival; Dioxins; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Female; HMGB1 Protein; Humans; Inflammation; Kelp; Lipopolysaccharides; Mice; Mice, Inbred ICR; Phloroglucinol; Spectrometry, Mass, Electrospray Ionization; Tannins; Toll-Like Receptor 4

Myrsinoic acid B (MAB) is a diprenylated benzoic acid widely found in the vegetal kingdom. Recent studies demonstrate that MAB has important antinociceptive effects in models of chemically or thermally induced nociception in mice.. In the present study we evaluated the effect of MAB in different models of inflammatory and neuropathic hypersensitivity in mice.. This study demonstrates that the pretreatment with MAB, given orally (8.4 to 83.8 μmol/kg), inhibited carrageenan- and complete Freund adjuvant-induced mechanical hypersensitivity. When administered after the induction of hypersensitivity, MAB also reduced the mechanical hypersensitivity in the ipsilateral and in the contralateral hindpaws of mice injected with complete Freund adjuvant, interfering with a signaling cascade already established. MAB reversed the hypersensitivity (mechanical and thermal) of operated animals, with similar results to those observed with gabapentin. MAB activity was evident when administered either systemically (PO or IV) or intrathecally, suggesting interference in the central pathways of pain control. Furthermore, MAB seems to present an antiinflammatory effect evidenced by the interference in both the neutrophil migration and in the increase of interleukin-1β levels after carrageenan injection. Of note, MAB treatment did not interfere with mechanical or thermal sensitivity in healthy mice, a frequent characteristic of commonly used analgesics, such as morphine or gabapentin. Side effects including interference in locomotor activity, motor performance, and body temperature in animals treated with MAB were absent.. MAB reduced mechanical and thermal hypersensitivity in mice submitted to models of inflammatory and neuropathic pain, showing excellent potential for treating persistent pain in humans.

Topics: Administration, Oral; Alkenes; Analgesics; Animals; Behavior, Animal; Benzofurans; Carrageenan; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Freund's Adjuvant; Hyperalgesia; Inflammation; Injections, Intravenous; Interleukin-1beta; Mice; Motor Activity; Neuralgia; Neutrophil Infiltration; Pain; Pain Measurement; Pain Threshold; Peroxidase; Time Factors

Salvianolic acid B (SalB), a bioactive compound isolated from the Chinese medicinal herb Danshen, has been shown to exert various anti-oxidative and anti-inflammatory activities in in vitro and in vivo studies. Here, we investigated the protective effects of SalB on traumatic brain injury (TBI) in mice. When administered within 2 h after TBI onset, SalB (25 mg/kg) reduced brain edema, lesion volume and motor functional deficits, and improved spatial learning and memory abilities. Moreover, SalB treatment inhibited the neutrophil infiltration and microglial activation at 48 h after TBI. Enzyme-linked immunosorbent assay (ELISA) for brain tissue homogenates was performed at 24 h after TBI to evaluate the expression of inflammation-related cytokines. The results showed that SalB suppressed the expression of pro-inflammatory cytokines TNF-α and IL-1β, whereas enhanced the expression of anti-inflammatory cytokines IL-10 and TGF-β1. All of these findings extended the protective role of SalB in the model of TBI and suggested that these protective effects might be associated with its anti-inflammatory activities. Thus SalB may have therapeutic potential for patients with TBI and perhaps other forms of acute brain injury.

Topics: Animals; Benzofurans; Brain Edema; Brain Injuries; Inflammation; Interleukin-10; Interleukin-1beta; Learning; Male; Memory; Mice; Mice, Inbred C57BL; Molecular Structure; Space Perception; Tumor Necrosis Factor-alpha

The aim of this study was assess the effect of collagen-based films containing usnic acid as a wound dressing for dermal burn healing. Second-degree burn wounds were performed in forty-five Wistar rats, assigned into nine groups: COL-animals treated with collagen-based films; PHO-animals treated with collagen films containing empty liposomes; UAL-animals treated with collagen-based films containing usnic acid incorporated into liposomes. After 7, 14, and 21 days the animals were euthanized. On 7th day there was a moderate infiltration of neutrophils, in UAL, distributed throughout the burn wounds, whereas in COL and PHO, the severity of the reaction was slighter and still limited to the margins of the burn wounds. On the 14th day, the inflammatory reaction was less intense in UAL, with remarkable plasma cells infiltration. On the 21st day, there was reduction of the inflammation, which was predominantly composed of plasma cells in all groups, particularly in UAL. The use of the usnic acid provided more rapid substitution of type-III for type-I collagen on the 14th day, and improved the collagenization density on the 21st day. It was concluded that the use of reconstituted bovine type-I collagen-based films containing usnic acid improved burn healing process in rats.

Topics: Actins; Animals; Benzofurans; Biological Dressings; Burns; Collagen; Collagen Type I; Collagen Type III; Immunohistochemistry; Inflammation; Liposomes; Male; Myofibroblasts; Rats; Rats, Wistar; Wound Healing

The biological properties of ailanthoidol, a neolignan from Zanthoxylum ailanthoides or Salvia miltiorrhiza Bunge, which is used in Chinese traditional herbal medicine, have not been evaluated. Here, we report that ailanthoidol inhibits inflammatory reactions in macrophages and protects mice from endotoxin shock. Our in vitro experiments showed that ailanthoidol suppressed the generation of nitric oxide (NO) and prostaglandin E(2) , as well as the expression of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 induced by lipopolysaccharide (LPS) in RAW264.7 cells. Similarly, ailanthoidol inhibited the production of inflammatory cytokines induced by LPS in RAW264.7 cells, including interleukin (IL)-1β and IL-6. In an animal model, ailanthoidol protected BALB/c mice from LPS-induced endotoxin shock, possibly through inhibition of the production of inflammatory cytokines and NO. Collectively, ailanthoidol inhibited the production of inflammatory mediators and may be a potential target for treatment of various inflammatory diseases.

Topics: Animals; Benzofurans; Cell Line; Flow Cytometry; Inflammation; Inflammation Mediators; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Microscopy, Fluorescence; NF-kappa B; Shock, Septic

alpha-Viniferin, an oligostilbene of trimeric resveratrol, has been reported to have anti-inflammatory potential in carrageenin-induced paw edema or adjuvant-induced arthritis in animal models. However, little is known about the molecular basis. In this study, alpha-viniferin at 3 - 10 microM dose-dependently inhibited interferon (IFN)-gamma-induced Ser(727) phosphorylation of the signal transducer and activation of transcription-1 (STAT-1), a pivotal transcription factor controlling IFN-gamma-targeted genes, in RAW 264.7 macrophages, and also IFN-gamma-induced activation of the extracellular signal-regulated kinase (ERK)-1, a protein kinase upstream of the Ser(727) phosphorylation of STAT-1. However, alpha-viniferin, only at a higher concentration of 10 microM, inhibited Janus kinase 2-mediated Tyr(701) phosphorylation of STAT-1 in the cells. To understand STAT-1-dependent inflammatory responses, we quantified nitric oxide (NO) or chemokines. alpha-Viniferin at 3 - 10 muM dose-dependently inhibited IFN-gamma-induced production of NO, IFN-gamma-inducible protein-10 (IP-10), or the monokine induced by IFN-gamma (MIG) in RAW 264.7 cells and also that of NO in primary macrophages-derived from C57BL/6 mice. Furthermore, alpha-viniferin diminished IFN-gamma-induced protein levels of inducible NO synthase (iNOS), attenuated mRNA levels of iNOS, IP-10, or MIG as well as inhibited promoter activity of the iNOS gene. In conclusion, this study proposes an anti-inflammatory mechanism of alpha-viniferin, down-regulating STAT-1-inducible inflammatory genes via inhibiting ERK-mediated STAT-1 activation in IFN-gamma-stimulated macrophages.

Topics: Animals; Base Sequence; Benzofurans; Blotting, Western; Cell Line; Chemokines; DNA Primers; Enzyme Activation; Enzyme-Linked Immunosorbent Assay; Inflammation; Interferon-gamma; Macrophages; Mice; Mice, Inbred C57BL; Nitric Oxide; Nitric Oxide Synthase Type II; Protein Kinases; Reverse Transcriptase Polymerase Chain Reaction; STAT1 Transcription Factor

Salvianolic acid B (Sal B) is a water-soluble compound found in the traditional Chinese medicine, Radix Salviae miltiorrhizae, and has been widely used to treat a variety of diseases in Asian cultures. Sal B was shown to inhibit apoptosis in many cell types, but its effect on hepatocyte apoptosis is unknown. In this study, we attempt to show that Sal B attenuates hepatocyte apoptosis and hepatic injury induced by lipopolysaccharide and D-galactosamine in mice. Sal B also inhibits apoptosis that is induced by the death receptor in the HL-7702 hepatocyte cell line. Apoptosis in vitro is determined by flow cytometry, DNA electrophoresis and high content screening assay. The antiapoptotic effect is generated by reducing the expression of tumor necrosis factor alpha receptor type 1, balancing the expression of Bcl-2 family members, decreasing the release of cytochrome C from the mitochondria into the cytosol and inhibiting activated Caspase-3. These findings suggest that Sal B can effectively inhibit hepatocyte apoptosis as well as the underlying mechanisms related to regulating mediators in death receptor and mitochondrial pathways.

Topics: Animals; Apoptosis; Benzofurans; Cell Line; DNA; DNA Fragmentation; Electrophoresis, Agar Gel; Flow Cytometry; Galactosamine; Hepatocytes; Humans; Inflammation; Lipopolysaccharides; Liver Diseases; Liver Function Tests; Male; Mice; Mitochondria; Receptors, Death Domain; Signal Transduction; Tumor Necrosis Factor-alpha

Many benzo[b]furan lignans are known to be biologically active in nature. 2-(3'-Methoxy-4'-hydroxy-phenyl)-5-(3-hydroxypropyl)-7-methoxy-benzo[b]furan-3-carbaldehyde (XH-14) is found as a bioactive component isolated from the plant Salvia miltiorrhiza, commonly known as Danshen, which is a traditional Chinese medicine that is used as a cardiovascular medication. This study examined whether 3 different XH-14 derivatives can inhibit adipocyte differentiation and induction of the adipokines visfatin and resistin in 3T3-L1 adipocytes. Adipocytes were cultured and differentiated in Dulbecco's modified Eagle medium containing fetal bovine serum, 3-isobytyl-1-methylxanthine, dexamethasone, and insulin for 6-8d in the absence and presence of 1-25μM XH-14-derived benzo[b]furan derivatives. Nontoxic 2-(3'-methoxy-4'-hydroxy-phenyl)-6-(3-hydroxypropyl)-5-methoxy-benzo[b]furan (5-MBF) at ≥5μM attenuated cellular lipid accumulation and down-regulated induction of peroxisome proliferator activated receptors γ (PPARγ) and CCAAT enhancer binding protein α (C/EBPα) in a dose-dependent manner, as evidenced by Oil Red O staining and Western blot analysis. Such inhibition of PPAR( and C/EBP( by 5-MBF was achieved at transcriptional mRNA levels. However, 2-(3'-methoxy-4'-hydroxy-phenyl)-5-(3-hydroxypropyl)-7-methoxy-benzo[b]furan (7-MBF) and 2-(3'-methoxy-4'-hydroxy-phenyl)-5-(3-hydroxypropyl)-7-methoxy-benzo[b]furan (6-MBF) had minimal effects on adipogenic differentiation, suggesting a structure-activity relationship of methoxybenzo[b]furan derivatives as an inhibitor of adipogenic differentiation. Furthermore, ≥5μM 5-MBF retarded protein and mRNA expression of proinflammatory and insulin resistance-enhancing adipokines of visfatin and resistin in differentiated adipocytes. Induction of visfatin and resistin was, at least in part, mediated via adipocyte differentiation-associated activation of PPARγ signal targeting adipocyte protein 2 and stearoyl-CoA desaturase. These results demonstrate that the 2-(3'-methoxy-4'-hydroxy-phenyl)-3-hydroxypropyl benzo[b]furan lignan, with a methoxy group at the 5-position on the benzene ring, may be a promising agent for disturbance of adipogenic differentiation and for blockage of obesity-associated inflammatory and metabolic diseases.

Topics: 3T3-L1 Cells; Adipocytes; Adipogenesis; Adipokines; Animals; Benzene; Benzofurans; CCAAT-Enhancer-Binding Protein-alpha; Cell Survival; Enzyme Induction; Furans; Gene Expression Regulation, Enzymologic; Guaiacol; Inflammation; Lipid Metabolism; Mice; Nicotinamide Phosphoribosyltransferase; PPAR gamma; Resistin; Salvia miltiorrhiza; Structure-Activity Relationship

The aim of the present study is to investigate the effects of Vam3 which is one of the dihydroxystilbene compounds on expressions of ICAM-1 in the lungs of OVA-induced asthmatic mice and the mechanisms of anti-airway inflammation. Balb/c mice were challenged with OVA inhalation. Lung tissues were stained with Mayer's hematoxylin and eosin for histopathologic examination. The expression of ICAM-1 in the lungs of mice was analyzed by Western blotting and immunohistochemistry method. The NF-kappaB activities were detected by NF-kappaB-luc reporter genetic transient transfection method. The activities of MMP-9 induced by LPS, TNF-alpha and PMA in THP-1 cells were determined by gelatin zymography method. The results showed that Vam3 could inhibit the expression of ICAM-1 in the OVA-induced mouse model. In addition, Vam3 could significantly suppress the activities of NF-kappaB in A549 cells and MMP-9 in THP-1 cells induced by LPS, TNF-alpha and PMA. These results suggested that Vam3 could alleviate the asthmatic inflammation by decreasing ICAM-1 expression in asthmatic mice, down regulating NF-kappaB and MMP-9 activities. Compound Vam3 showed inhibitory effects on inflammatory signal pathways involved in asthma.

Topics: Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Benzofurans; Cell Line, Tumor; Humans; Inflammation; Intercellular Adhesion Molecule-1; Leukemia, Myeloid; Lung; Lung Neoplasms; Male; Matrix Metalloproteinase 9; Mice; Mice, Inbred BALB C; NF-kappa B; Ovalbumin; Stilbenes

Cyclooxygenase (COX)-2 is among the endothelial genes upregulated by uniform laminar shear stress (LSS), characteristically associated with atherosclerotic lesion-protected areas. We have addressed whether the induction of COX-2-dependent prostanoids in endothelial cells by LSS plays a role in restraining endothelial tumor necrosis factor (TNF)-alpha generation, a proatherogenic cytokine, through the induction of heme oxygenase-1 (HO)-1, an antioxidant enzyme. In human umbilical vein endothelial cells (HUVECs) exposed to steady LSS of 10 dyn/cm(2) for 6 hours, COX-2 protein was significantly induced, whereas COX-1 and the downstream synthases were not significantly modulated. This was associated with significant (P<0.05) increase of 6-keto-prostaglandin (PG)F(1alpha) (the hydrolysis product of prostacyclin), PGE(2), and PGD(2). In contrast, TNF-alpha released in the medium in 6 hours (3633+/-882 pg) or detected in cells lysates (1091+/-270 pg) was significantly (P<0.05) reduced versus static condition (9100+/-2158 and 2208+/-300 pg, respectively). Coincident induction of HO-1 was detected. The finding that LSS-dependent reduction of TNF-alpha generation and HO-1 induction were abrogated by the selective inhibitor of COX-2 NS-398, the nonselective COX inhibitor aspirin, or the specific prostacyclin receptor (IP) antagonist RO3244794 illuminates the central role played by LSS-induced COX-2-dependent prostacyclin in restraining endothelial inflammation. Carbacyclin, an agonist of IP, induced HO-1. Similarly to inhibition of prostacyclin biosynthesis or activity, the novel imidazole-based HO-1 inhibitor QC15 reversed TNF-alpha reduction by LSS. These findings suggest that inhibition of COX-2-dependent prostacyclin might contribute to acceleration of atherogenesis in patients taking traditional nonsteroidal antiinflammatory drugs (NSAIDs) and NSAIDs selective for COX-2 through downregulation of HO-1, which halts TNF-alpha generation in human endothelial cells.

Topics: 6-Ketoprostaglandin F1 alpha; Aspirin; Atherosclerosis; Benzofurans; Cells, Cultured; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Dinoprost; Dinoprostone; Down-Regulation; Endothelial Cells; Epoprostenol; Heme Oxygenase-1; Humans; Inflammation; Nitrobenzenes; Perfusion; Propionates; Prostaglandin D2; Receptors, Epoprostenol; Receptors, Prostaglandin; Stress, Mechanical; Sulfonamides; Tumor Necrosis Factor-alpha; Up-Regulation

Glucocorticoids are highly effective in the therapy of inflammatory diseases. Their value, however, is limited by side effects. The discovery of the molecular mechanisms of the glucocorticoid receptor and the recognition that activation and repression of gene expression could be addressed separately opened the possibility of achieving improved safety profiles by the identification of ligands that predominantly induce repression. Here we report on ZK 245186, a novel, non-steroidal, low-molecular-weight, glucocorticoid receptor-selective agonist for the topical treatment of inflammatory dermatoses.. Pharmacological properties of ZK 245186 and reference compounds were studied in terms of their potential anti-inflammatory and side effects in functional bioassays in vitro and in rodent models in vivo.. Anti-inflammatory activity of ZK 245186 was demonstrated in in vitro assays for inhibition of cytokine secretion and T cell proliferation. In vivo, using irritant contact dermatitis and T cell-mediated contact allergy models in mice and rats, ZK 245186 showed anti-inflammatory efficacy after topical application similar to the classical glucocorticoids, mometasone furoate and methylprednisolone aceponate. ZK 245186, however, exhibits a better safety profile with regard to growth inhibition and induction of skin atrophy after long-term topical application, thymocyte apoptosis, hyperglycaemia and hepatic tyrosine aminotransferase activity.. ZK 245186 is a potent anti-inflammatory compound with a lower potential for side effects, compared with classical glucocorticoids. It represents a promising drug candidate and is currently in clinical trials.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Benzofurans; Drug Evaluation, Preclinical; Inflammation; Mice; Mice, Inbred Strains; Pentanols; Quinolines; Rats; Rats, Wistar; Receptors, Glucocorticoid; Sensitivity and Specificity; Skin; Skin Diseases

Lithospermic acid (LSA) was originally isolated from the roots of Salvia mitiorrhiza, a common herb of oriental medicine. Previous studies demonstrated that LSA has antioxidant effects. In this study, we investigated the in vitro xanthine oxidase (XO) inhibitory activity, and in vivo hypouricemic and anti-inflammatory effects of rats. XO activity was detected by measuring the formation of uric acid or superoxide radicals in the xanthine/xanthine oxidase system. The results showed that LSA inhibited the formation of uric acid and superoxide radicals significantly with an IC50 5.2 and 1.08 microg/ml, respectively, and exhibited competitive inhibition. It was also found that LSA scavenged superoxide radicals directly in the system beta-NADH/PMS and inhibited the production of superoxide in human neutrophils stimulated by PMA and fMLP. LSA was also found to have hypouricemic activity on oxonate-pretreated rats in vivo and have anti-inflammatory effects in a model of gouty arthritis. These results suggested that LSA is a competitive inhibitor of XO, able to directly scavenge superoxide and inhibit superoxide production in vitro, and presents hypouricemic and anti-inflammatory actions in vivo.

Topics: Allopurinol; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Gouty; Benzofurans; Depsides; Disease Models, Animal; Dose-Response Relationship, Drug; Enzyme Inhibitors; Humans; Hyperuricemia; Inflammation; Male; Molecular Conformation; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Oxonic Acid; Rats; Rats, Wistar; Reactive Oxygen Species; Tetradecanoylphorbol Acetate; Uric Acid; Xanthine Oxidase

This study was designed to determine the effect of inhibitors of cyclooxygenase (COX)-1, COX-2, and the nonselective COX inhibitor naproxen on coronary vasoactivity and thrombogenicity under baseline and lipopolysaccharide (LPS)-induced inflammatory conditions. We hypothesize that endothelial COX-1 is the primary COX isoform in the canine normal coronary artery, which mediates arachidonic acid (AA)-induced vasodilatation. However, COX-2 can be induced and overexpressed by inflammatory mediators and becomes the major local COX isoform responsible for the production of antithrombotic prostaglandins during systemic inflammation. The interventions included the selective COX-1 inhibitor SC-560 (0.3 mg/kg iv), the selective COX-2 inhibitor nimesulide (5 mg/kg iv), or the nonselective COX inhibitor naproxen (3 mg/kg iv). The selective prostacyclin (IP) receptor antagonist RO-3244794 (RO) was used as an investigational tool to delineate the role of prostacyclin (PGI(2)) in modulating vascular reactivity. AA-induced vasodilatation of the left circumflex coronary artery was suppressed to a similar extent by each of the COX inhibitors and RO. The data suggest that AA-induced vasodilatation in the normal coronary artery is mediated by a single COX isoform, the constitutive endothelial COX-1, which is reported to be susceptible to COX-2 inhibitors. The effect of the COX inhibitors on thrombus formation was evaluated in a model of carotid artery thrombosis secondary to electrolytic-induced vessel wall injury. Pretreatment with LPS (0.5 mg/kg iv) induced a systemic inflammatory response and prolonged the time-to-occlusive thrombus formation, which was reduced in the LPS-treated animals by the administration of nimesulide. In contrast, neither SC-560 nor naproxen influenced the time to thrombosis in the animals pretreated with LPS. The data are of significance in view of reported adverse cardiovascular events observed in clinical trials involving the use of selective COX-2 inhibitors, thereby suggesting that the endothelial constitutive COX-1 and the inducible vascular COX-2 serve important functions in maintaining vascular homeostasis.

Topics: Acetylcholine; Animals; Arachidonic Acid; Benzofurans; Carotid Arteries; Coronary Circulation; Coronary Vessels; Cyclooxygenase 1; Cyclooxygenase 2; Cyclooxygenase 2 Inhibitors; Cyclooxygenase Inhibitors; Disease Models, Animal; Dogs; Dose-Response Relationship, Drug; Electric Stimulation; Epoprostenol; Inflammation; Ligation; Lipopolysaccharides; Naproxen; Platelet Aggregation; Propionates; Pyrazoles; Receptors, Epoprostenol; Sulfonamides; Thrombosis; Time Factors; Vasodilation; Vasodilator Agents

The role of specific nicotinic receptor (nAChR) subtypes in antinociception has not been fully elucidated because of the lack, until recently, of selective tool compounds. (R)-N-(1-azabicyclo[2.2.2]oct-3-yl)(5-(2-pyridyl)thiopene-2-carboxamide) (compound B) is reported to be an agonist selective for the alpha(7)nAChR and in the present study was found to be efficacious in inflammatory pain models in 2 species. Compound B reversed complete Freund adjuvant-induced reductions in paw withdrawal thresholds in rat and mouse in a dose-related manner, producing maximum reversals of 65% +/- 4% at 10 mg/kg and 87% +/- 15% at 20 mg/kg. When rats and mice were predosed with the centrally penetrant, broad-spectrum nicotinic receptor antagonist mecamylamine, the efficacy of the agonist was significantly inhibited, producing reversals of only 11% +/- 5% at 10 mg/kg and 5% +/- 13% at 20 mg/kg, confirming activity via nicotinic receptors. Rats were also predosed systemically with the selective low-brain penetrant alpha(7)-antagonist methyllycaconitine, which had no effect on agonist activity (90% +/- 18% at 10 mg/kg), suggesting a central involvement. This hypothesis was further established with methyllycaconitine completely inhibited the agonist effect when dosed intrathecally (1% +/- 7%).. These studies provide good rationale for the utility of selective, central nervous system penetrant agonists at the alpha(7)-nicotinic receptor for the treatment of inflammatory pain.

Topics: Aconitine; alpha7 Nicotinic Acetylcholine Receptor; Animals; Behavior, Animal; Benzofurans; Dose-Response Relationship, Drug; Female; Freund's Adjuvant; Hyperalgesia; Inflammation; Injections, Intraperitoneal; Male; Mecamylamine; Mice; Mice, Inbred C57BL; Models, Animal; Nicotinic Antagonists; Pain; Pain Measurement; Quinuclidines; Rats; Receptors, Nicotinic; Weight-Bearing

Enhanced endoplasmic reticulum (ER) stress has been implicated in various pathological situations including inflammation. During a search for compounds that regulate ER stress, we identified vaticanol B, a tetramer of resveratrol, as an agent that protects against ER stress-induced cell death. Vaticanol B suppressed the induction of unfolded protein response-targeted genes such as glucose-regulated protein 78 (GRP78) and C/EBP-homologous protein (CHOP) after cells were treated with ER stressors. Analysis in the mouse macrophage cell line RAW 264.7 revealed that vaticanol B also possesses a strong anti-inflammatory activity. Production of a variety of inflammatory modulators such as tumor necrosis factor-alpha, nitric oxide, and prostaglandin E(2) was inhibited by vaticanol B to a much greater extent than by monomeric or dimeric resveratrol after exposure of cells to lipopolysaccharide. Further investigations to determine the common mechanisms underlying the regulation of ER stress and inflammation by vaticanol B disclosed an important role for vaticanol B in regulation of basic gene expression and in prevention of the protein leakage from the ER into the cytosol in both conditions. These results suggest that vaticanol B is a novel anti-inflammatory agent that improves the ER environment by reducing the protein load on the ER and by maintaining the membrane integrity of the ER.

Topics: Animals; Anti-Inflammatory Agents; Benzofurans; Cell Line, Tumor; Cell Survival; Dinoprostone; Dose-Response Relationship, Drug; Endoplasmic Reticulum; Endoplasmic Reticulum Chaperone BiP; Gene Expression; Heat-Shock Proteins; Inflammation; Intracellular Membranes; Lipopolysaccharides; Macrophages; Mice; Molecular Chaperones; Nitric Oxide; Phenols; Protein Biosynthesis; Stress, Physiological; Thapsigargin; Transcription Factor CHOP; Tumor Necrosis Factor-alpha; Tunicamycin

Some agonists of the peroxisome proliferator-activated receptor gamma (PPARgamma) belonging to the thiazolidinedione (TZD) family, as well as the cyclopentenone prostaglandin 15-dPGJ2, have been shown to cause neuroprotection in animal models of stroke. We have tested whether the TZD-unrelated PPARgamma agonist L-796,449 is neuroprotective after permanent middle cerebral artery occlusion (MCAO) in the rat brain. Our results show that L-796,449 decreases MCAO-induced infarct size and improves neurologic scores. This protection is concomitant to inhibition of MCAO-induced brain expression of inducible NO synthase (iNOS) and the matrix metalloproteinase MMP-9 and to upregulation of the cytoprotective stress protein heme oxygenase-1 (HO-1). Analysis of the NF-kappaB p65 monomer and the NF-kappaB inhibitor IkappaBalpha protein levels as well as gel mobility shift assays indicate that L-796,449 inhibits NF-kappaB signaling, and that it may be recruiting both PPARgamma-dependent and independent pathways. In summary, our results provide new insights for stroke treatment.

Topics: Animals; Benzofurans; Blotting, Western; Brain Ischemia; Caspase 3; Caspases; Cyclooxygenase 2; Disease Models, Animal; Electrophoretic Mobility Shift Assay; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; I-kappa B Proteins; Inflammation; Male; Matrix Metalloproteinase 9; Neuroprotective Agents; NF-kappa B; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Phenylacetates; PPAR gamma; Prostaglandin-Endoperoxide Synthases; Rats

Nuclear factor-kappaB (NF-kappaB) is a ubiquitous rapid response transcription factor involved in inflammatory reactions which exerts its effect by expressing cytokines, chemokines, and cell adhesion molecules. Oxidative stress causes NF-kappaB activation. IRFI 042 is a novel dual vitamin E-like antioxidant and we, therefore, investigated its ability to protect the heart from oxidative stress and to halt the inflammatory response in a model of myocardial ischaemia-reperfusion injury.. Anaesthetized rats were subjected to total occlusion (45 min) of the left main coronary artery followed by 5-h reperfusion (MI/R). Sham myocardial ischaemia rats (sham-operated rats) were used as controls. Myocardial necrosis, cardiac output, cardiac and plasma vitamin E levels, myocardial malondialdehyde (MAL), cardiac SOD activity and elastase content (an index of leukocyte infiltration), hydroxyl radical (OH&z.ccirf;) formation, cardiac amount of mRNA codifying for ICAM-1 (evaluated by the means of reverse transcriptase polymerase chain reaction) and ICAM-1 immunostaining in the at-risk myocardium were investigated. NF-kappaB activation and the inhibitory protein of NF-kappaB, I-kappaBalpha, were also studied in at-risk myocardium by using electrophoretic mobility shift assay (EMSA) and Western blot analysis, respectively.. The ischaemia-reperfusion model produced wide heart necrosis (area at risk-necrotic area=52+/-5%; necrotic area-left ventricle=28+/-3%), increased cardiac MAL, an index of lipid peroxidation (area at risk=62.5+/-3.9 nmol/g tissue; necrotic area=80.3+/-5.1 nmol/g tissue), induced tissue neutrophil infiltration, and caused a marked decrease in endogenous antioxidants. Furthermore, myocardial ischaemia plus reperfusion caused in the area at risk peak message for ICAM-1 at 3 h of reperfusion and increased cardiac ICAM-1 immunostaining at 5 h of reperfusion. NF-kappaB activation was also evident at 0.5 h of reperfusion and reached its maximum at 2 h of reperfusion. I-kappaBalpha was markedly decreased at 45 min of occlusion; peak reduction was observed at 1 h of reperfusion and thereafter it was gradually restored. Intraperitoneal administration of IRFI 042 (5, 10, 20 mg/kg, 5 min after reperfusion) reduced myocardial necrosis expressed as a percentage either of the area at risk (18+/-4%) or the total left ventricle (11+/-2%), and improved cardiac output. This treatment also limited membrane lipid peroxidation in the area at risk (MAL=14.3+/-2.5 nmol/g tissue) and in the necrotic area (MAL=26.5+/-3.7 nmol/g tissue), restored the endogenous antioxidants vitamin E and superoxide dismutase, and inhibited detrimental hydroxyl radical formation. Finally, IRFI 042 blocked the activation of NF-kappaB, reduced cardiac ICAM-1 expression, and blunted tissue elastase content, an index of leukocytes accumulation at the site of injury.. Our data suggest that IRFI 042 is cardioprotective during myocardial infarction by limiting reperfusion-induced oxidative stress and by halting the inflammatory response.

Topics: Analysis of Variance; Animals; Antioxidants; Benzofurans; Cytoplasm; Hydroxyl Radical; I-kappa B Proteins; Immunohistochemistry; Inflammation; Intercellular Adhesion Molecule-1; Lipid Peroxidation; Male; Myocardial Reperfusion Injury; Myocardium; NF-kappa B; Oxidative Stress; Pancreatic Elastase; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; RNA; Superoxide Dismutase; Vitamin E

To evaluate the degree of neutrophil infiltration into ischemic tissue after transient focal cerebral ischemia, and to examine the effects of chiral 3-n-butylphthalide (NBP) on this inflammatory process.. After a 24-h reperfusion following transient cerebral ischemia, two different techniques, histologic analysis and modified myeloperoxidase (MPO)-quantification method, were utilized to identify the infiltration of neutrophils into cerebral tissue following ischemia. The expression of intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor-alpha(TNF-alpha) in the ischemic zone were observed by immunohistochemistry, Western blot, and in situ hybridization techniques.. In cerebral cortex area perfused by middle cerebral artery (MCA), MPO activity was greatly increased after 24 h of reperfusion in the vehicle group, and it correlated well with the infiltration of neutrophils. Administration of dl-, d-, and l-NBP (20 mg.kg-1) partially inhibited both the increase in MPO activity and the appearance of neutrophils in ischemia-reperfusion sites. Up-regulation of ICAM-1 was also observed on the microvessel endothelium in the ischemic territory. In addition, chiral NBP markedly blunted ICAM-1 expression, and decreased the number of TNF-alpha blue purple-positive neurons induced by ischemia-reperfusion injury.. The results indicate that the increase in neutrophils infiltration into the infarct site implicated postischemic brain injury, and NBP was effective in protecting the ischemic sites following ischemic insult.

Topics: Animals; Benzofurans; Brain Ischemia; Cerebral Cortex; Infarction, Middle Cerebral Artery; Inflammation; Intercellular Adhesion Molecule-1; Leukocyte Count; Male; Neuroprotective Agents; Neutrophils; Peroxidase; Rats; Rats, Wistar; Reperfusion Injury; RNA, Messenger; Tumor Necrosis Factor-alpha

The present study examined analgesia produced by S and R isomers of the novel 5-HT3 receptor antagonists, ADR-851 and ADR-882 (0.1-10 mg/kg s.c.) against acute thermal, mechanical and formalin-induced inflammatory pain in rats. Neither isomer of ADR-851 or ADR-882 was analgesic in the thermal or mechanical test. Similarly, neither S or R forms of ADR-882 produced significant anti-nociception in the formalin test. In contrast, ADR-851R produced significant analgesia at 3 and 10 mg/kg doses in this test, while ADR-851S produced significant analgesia only at 1 mg/kg.

Topics: Analgesics; Animals; Behavior, Animal; Benzofurans; Bridged Bicyclo Compounds; Bridged Bicyclo Compounds, Heterocyclic; Formaldehyde; Inflammation; Male; Metoclopramide; Motor Activity; Nociceptors; Pain; Rats; Rats, Inbred Strains; Respiration; Serotonin Antagonists; Stereoisomerism

During inflammation polymorphonuclear cells (PMNs) are exposed to agonistic stimuli including activated complement, kallikrein, arachidonic acid metabolites, monokines, and platelet-activating factor (PAF). We report that PAF not only directly activates PMNs but in miniscule quantities (10(-12) mol/L) "primes" them as well, that is, permits PMNs to respond to subsequent stimuli that would be otherwise ineffectual. PAF priming of responses including superoxide generation, elastase release, and aggregation is time dependent and is maximal within five minutes. PAF need not be present during the subsequent exhibition of PMN agonists, but priming is inhibited by cold and is also inhibited by the PAF receptor antagonists BN 52021, L-652, and kadsurenone. An intact PAF molecule is required because lyso-PAF and methoxy-PAF do not prime PMN responses. PAF priming is associated with both enhanced expression of the adhesive glycoprotein identified by OKM-1 antibody and an enhanced rise in intracellular calcium levels in response to the subsequent addition of agonists such as FMLP. PMNs primed with PAF and stimulated with either F-Met-Leu-Phe or phorbol esters are more effective in lysing and detaching cultured human endothelial cells--damage that can also be inhibited by the PAF antagonists. Because PAF is synthesized and exhibited on surfaces of endothelial cells perturbed by coagulation, we suggest that this lipid may potentiate otherwise trivial activators of marginated PMNs so that they become damaging to the PAF-synthesizing endothelium itself. If so, our studies suggest a possible therapeutic role for PAF inhibitors in excessive inflammatory states.

Topics: Benzofurans; Cell Aggregation; Cell Survival; Diterpenes; Endothelium, Vascular; Fetal Hemoglobin; Furans; Ginkgolides; Hemoglobins, Abnormal; Humans; Inflammation; Lactones; Lignans; N-Formylmethionine Leucyl-Phenylalanine; Neutrophils; Pancreatic Elastase; Platelet Activating Factor; Platelet Membrane Glycoproteins; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Superoxides

Amiodarone, a cardiac antiarrhythmic agent, has been associated with the development of interstitial pulmonary fibrosis in patients receiving prolonged therapy with the drug. To further assess the toxic effects of amiodarone on lung tissue, Syrian hamsters were given a single intratracheal insufflation of the agent and evaluated for histologic evidence of lung injury. Control animals received intratracheal insufflations of the vehicle in which amiodarone was dissolved. After an initial, transient alveolitis in both experimental and control animals, the amiodarone-treated lungs developed increased interstitial thickening due to fibrinous exudates, alveolar epithelial hyperplasia, inflammatory cell infiltrates, and marked deposition of collagen manifested on trichrome staining. Controls, in contrast, showed nearly complete resolution of the initial alveolitis. An unusual feature of the amiodarone-induced lung injury was reemergence of the alveolitis between 5 and 14 days, which included a marked influx of eosinophils into the lung. Although the precise mechanism of the lung injury is not known, the persistence of the acute inflammatory cells as well as the presence of eosinophils suggests a hypersensitivity-type reaction. Furthermore, the progression of lung injury to fibrosis after a single insult with the drug suggests that mere discontinuation of amiodarone therapy in humans may not reverse the disease process, but that corticosteroid therapy may also be required. Amiodarone appears to be a useful agent to induce diffuse fibrotic reactions in the lung that morphologically resemble idiopathic pulmonary fibrosis in humans.

Topics: Amiodarone; Animals; Benzofurans; Cricetinae; Hemorrhage; Inflammation; Lung; Lung Diseases; Mesocricetus; Pulmonary Fibrosis

Topical application of 400 mug of cantharidin to the rat's ear caused an approximate doubling in the mean weight of uniform ear punch samples when compared to vehicle-treated controls at 72 hr, and produced a maximal response at 7 days. Dexamethasone reduced the increase in weight when applied topically, but was ineffective when given subcutaneously or orally at the same doses. Hydrocortisone, prednisolone, triamcinolone, betamethasone, flurometholone, paramethasone acetate, fluocinolone acetonide, fluocinonide, and flurandrenolide showed significant suppression of cantharidin-induced inflammation. Cholesterol, diphenhydramine, tripelennamine, chlorpheniramine, promethazine, cyproheptadine, epinephrine, phenylephrine, alpha-tocopherol, indomethacin, and bufexamac were inactive. It is suggested that the procedure employed may be useful in the screening and evaluation of topical anti-inflammatory agents.

Topics: Administration, Topical; Animals; Anti-Inflammatory Agents; Benzofurans; Dexamethasone; Glucocorticoids; Inflammation; Male; Rats

A series of 2,3-dihydrobenzofuran-5-acetic acids and related compounds was prepared as potential antiinflammatory agents. As measured by the carrageenan-induced edema method for the preliminary screening test, introduction of a methyl group alpha to the acetic acid function enhanced the antiinflammatory activity, and alpha-(7-chloro-2,2-dimethyl-2,3-dihydrobenzofuran)-alpha-methyl-5-acetic acid (13a) showed the most potent activity in this series.

Topics: Acetates; Animals; Anti-Inflammatory Agents; Benzofurans; Carrageenan; Edema; Gastric Mucosa; Inflammation; Male; Rats; Structure-Activity Relationship

Topics: Adrenalectomy; Analgesics; Animals; Anti-Inflammatory Agents; Arthritis; Benzofurans; Butyrates; Carrageenan; Dose-Response Relationship, Drug; Edema; Fever; Freund's Adjuvant; Inflammation; Male; Mycobacterium; Phenylbutazone; Rats; Rats, Inbred Strains; Time Factors; Yeasts