curcumin and Liver-Cirrhosis

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a common cause of chronic liver disease and can progress to nonalcoholic steatohepatitis and cirrhosis. This study aims to summarize the evidence for the effects of curcumin on MAFLD progression. Studies were identified from Medline and Scopus databases until April 2022. Systematic reviews and meta-analyses (SRMA) and randomized controlled trials (RCT) were selected based on pre-specified criteria. Three reviewers independently extracted data and assessed quality of included studies. Of the 427 identified records, 6 SRMAs and 16 RCTs were included in the analysis. Very high overlap was observed among SRMAs with corrected covered area of 21.9%. From an updated meta-analysis, curcumin demonstrated significant improvement in aspartate and alanine aminotransferase with pooled mean difference [95% confidence interval (CI)] of -3.90 (-5.97, -1.82) and -5.61 (-9.37, -1.85) units/L, respectively. Resolution and improvement of hepatic steatosis was higher in curcumin than control group with pooled relative risk (95% CI) of 3.53 (2.01, 6.22) and 3.41 (1.36, 8.56), respectively. Curcumin supplementation also led to lower fasting blood sugar, body mass index, and total cholesterol. Further trials should be conducted to assess the effect of curcumin on liver histology, especially regarding non-invasive hepatic fibrosis and steatosis.

Topics: Curcumin; Humans; Iran; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Thailand

Medicinal plants with minimal side effects, low cost, and liver-protective effects can be a suitable treatment option for cirrhosis. Therefore, this systematic review aimed to determine the effectiveness of herbal medicines on cirrhosis, a life-threatening liver disease. PubMed, Scopus, Web of Science, and Google Scholar were systematically searched for clinical trials that investigated the effect of medicinal plants on cirrhosis. This review includes 11 clinical trials, of which eight studies including 613 patients assessed the effect of silymarin on cirrhosis. Three of six studies showed the beneficial effects of silymarin on aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Two studies including 118 patients investigated the effect of curcumin on cirrhosis, one showing improvement in quality of life and the other showing improvements in alkaline phosphatase (ALP), bilirubin, prothrombin time (PT), and the international normalized ratio (INR). An article including four patients investigated the effect of ginseng on cirrhosis; two patients reported improvement in the Child-Pugh score, and ascites decreased in two. All studies included here reported no or negligible side effects. Results showed that medicinal plants including silymarin, curcumin, and ginseng have beneficial effects on cirrhosis. However, due to the limited number of studies, further high-quality studies are warranted.

Topics: Curcumin; Humans; Liver Cirrhosis; Plants, Medicinal; Quality of Life; Silymarin

Hepatic fibrosis is a great concern in public health. While effective drugs for its treatment are lacking, Curcuma longa L. (CL) has been reported as a promising therapeutic. We aimed to uncover the core components and mechanisms of CL against hepatic fibrosis via a network pharmacology approach.. The main components of CL were obtained and screened. While targets of components and disease were respectively collected using SwissTargetPrediction and online databases, common targets were assessed. A protein-protein interaction (PPI) network was constructed, and core targets were identified. GO and KEGG pathway enrichment analyses were performed, and molecular docking was conducted to validate the binding of core components in CL on predicted core targets.. Nine main components from CL based on high-performance liquid chromatography (HPLC) and 63 anti-fibrosis targets were identified, and a PPI network and a component target-disease target network were constructed. Apigenin, quercetin, demethoxycurcumin, and curcumin are likely to become key phenolic-based components and curcuminoids for the treatment of hepatic fibrosis, respectively. KEGG pathway enrichment analysis revealed that the HIF-1 signaling pathway (hsa04066) was most significantly enriched. Considering core targets of the PPI network and a network of the common targets and pathways enriched, AKT1, MAPK1, EGFR, MTOR, and SRC may be the core potential targets of CL against hepatic fibrosis. Molecular docking was carried out to verify the binding of above core components to core targets.. The therapeutic effect of CL on hepatic fibrosis may be attributed to multi-components, multi-targets, and multi-pathways.

Topics: Curcuma; Drugs, Chinese Herbal; Humans; Liver Cirrhosis; Molecular Docking Simulation; Network Pharmacology; Protein Interaction Maps

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

Immune modulation is a very modern medical field for targeting viral infections. In the race to develop the best immune modulator against viruses, curcumin, as a natural product, is inexpensive, without side effects, and can stimulate very well certain areas of the human immune system. As a bright yellow component of turmeric spice, curcumin has been the subject of thousands of scientific and clinical studies in recent decades to prove its powerful antioxidant properties and anticancer effects. Curcumin has been shown to influence inter- and intracellular signaling pathways, with direct effects on gene expression of the antioxidant proteins and those that regulate the immunity. Experimental studies have shown that curcumin modulates several enzyme systems, reduces nitrosative stress, increases the antioxidant capacity, and decreases the lipid peroxidation, protecting against fatty liver pathogenesis and fibrotic changes. Hepatitis B virus (HBV) affects millions of people worldwide, having sometimes a dramatic evolution to chronic aggressive infection, cirrhosis, and hepatocellular carcinoma. All up-to-date treatments are limited, there is still a gap in the scientific knowledge, and a sterilization cure may not yet be possible with the removal of both covalently closed circular DNA (cccDNA) and the embedded HBV DNA. With a maximum light absorption at 420 nm, the cytotoxicity of curcumin as photosensitizer could be expanded by the intravenous blue laser blood irradiation (IVBLBI) or photobiomodulation in patients with chronic hepatitis B infection, Hepatitis B e-antigen (HBeAg)-positive, noncirrhotic, but nonresponsive to classical therapy. Photobiomodulation increases DNA repair by the biosynthesis of complex molecules with antioxidant properties, the outset of repairing enzyme systems and new phospholipids for regenerating the cell membranes. UltraBioavailable Curcumin and blue laser photobiomodulation could suppress the virus and control better the disease by reducing inflammation/fibrosis and stopping the progression of chronic hepatitis, reversing fibrosis, and diminishing the progression of cirrhosis, and decreasing the incidence of hepatocellular carcinoma. Photodynamic therapy with blue light and curcumin opens new avenues for the effective prevention and cure of chronic liver infections and hepatocellular carcinoma. Blue laser light and UltraBioavailable Curcumin could be a new valuable alternative for medical applications in chronic B viral hepat

Topics: Antineoplastic Agents, Phytogenic; Antioxidants; Carcinoma, Hepatocellular; Curcumin; DNA Repair; DNA, Circular; DNA, Viral; Hepatitis B e Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Immunologic Factors; Liver; Liver Cirrhosis; Liver Neoplasms; Low-Level Light Therapy; Photosensitizing Agents

Monocytes and macrophages are important cells of the innate immune system that have diverse functions, including defense against invading pathogens, removal of dead cells by phagocytosis, antigen presentation in the context of MHC class I and class II molecules, and production of various pro-inflammatory cytokines and chemokines such as IL-1β, IL-6, TNF-α and MCP-1. In addition, pro-inflammatory (M1) and anti-inflammatory (M2) macrophages clearly play important roles in the progression of several inflammatory diseases. Therefore, therapies that target macrophage polarization and function by either blocking their trafficking to sites of inflammation, or skewing M1 to M2 phenotype polarization may hold clinical promise in several inflammatory diseases. Dietary-derived polyphenols have potent natural anti-oxidative properties. Within this group of polyphenols, curcumin has been shown to suppress macrophage inflammatory responses. Curcumin significantly reduces co-stimulatory molecules and also inhibits MAPK activation and the translocation of NF-κB p65. Curcumin can also polarize/repolarize macrophages toward the M2 phenotype. Curcumin-treated macrophages have been shown to be highly efficient at antigen capture and endocytosis via the mannose receptor. These novel findings provide new perspectives for the understanding of the immunopharmacological role of curcumin, as well as its therapeutic potential for impacting macrophage polarization and function in the context of inflammation-related disease. However, the precise effects of curcumin on the migration, differentiation, polarization and immunostimulatory functions of macrophages remain unknown. Therefore, in this review, we summarized whether curcumin can influence macrophage polarization, surface molecule expression, cytokine and chemokine production and their underlying pathways in the prevention of inflammatory diseases.

Topics: Alzheimer Disease; Animals; Antigen Presentation; Atherosclerosis; Cell Movement; Cell Polarity; Curcumin; Cytokines; Diet; Humans; Immunologic Factors; Infections; Liver Cirrhosis; Macrophages; Neoplasms; Obesity

Increasing prevalence of nonalcoholic fatty liver disease (NAFLD) in parallel with the obesity epidemic has been a major public health concern. NAFLD is the most common chronic liver disease in the United States, ranging from fatty liver to steatohepatitis, fibrosis and cirrhosis in the liver. In response to chronic liver injury, fibrogenesis in the liver occurs as a protective response; however, prolonged and dysregulated fibrogenesis can lead to liver fibrosis, which can further progress to cirrhosis and eventually hepatocellular carcinoma. Interplay of hepatocytes, macrophages and hepatic stellate cells (HSCs) in the hepatic inflammatory and oxidative milieu is critical for the development of NAFLD. In particular, HSCs play a major role in the production of extracellular matrix proteins. Studies have demonstrated that bioactive food components and natural products, including astaxanthin, curcumin, blueberry, silymarin, coffee, vitamin C, vitamin E, vitamin D, resveratrol, quercetin and epigallocatechin-3-gallate, have antifibrotic effects in the liver. This review summarizes current knowledge of the mechanistic insight into the antifibrotic actions of the aforementioned bioactive food components.

Topics: Blueberry Plants; Coffee; Curcumin; Food; Hepatic Stellate Cells; Hepatocytes; Humans; Liver Cirrhosis; Macrophages; Non-alcoholic Fatty Liver Disease; Oxidative Stress; Resveratrol; Vitamins; Xanthophylls

Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that consists of two subunits, the HIF-1α and HIF-1β (ARNT). Under hypoxic conditions, HIF-1 is an adaptive system that regulates the transcription of multiple genes associated with growth, angiogenesis, proliferation, glucose transport, metabolism, pH regulation and cell death. However, aberrant HIF-1 activation contributes to the pathophysiology of several human diseases such as cancer, ischemic cardiovascular disorders, and pulmonary and kidney diseases. A growing body of evidence indicates that curcumin, a natural bioactive compound of turmeric root, significantly targets both HIF-1 subunits, but is more potent against HIF-1α. In this review, we have summarized the knowledge about the pharmacological effects of curcumin on HIF-1 and the related molecular mechanisms that may be effective candidates for the development of multi-targeted therapy for several human diseases.

Topics: Animals; Curcumin; Humans; Hypoxia-Inducible Factor 1; Liver Cirrhosis; Metabolic Diseases; Neoplasms; Vascular Remodeling

Accurate. Since sCD30 levels and sCD26/sCD30 ratios may contribute to the activity of the disease, they may be used to assess ITP disease activity.. hBMSCs and hFOB1.19 cells modulate the phenotype of PC3 prostate cancer cells and the expression of CD59 by activating the RANK/RANKL/OPG signaling pathway.. Results showed that the EEG responses at lower levels of the independent variables were significantly high than at higher levels; except for oxygen content, the EEG responses at lower levels were considerably lower than at a higher level. It also showed that an upsurge in the physical demand increased lifting frequency and replication and caused decreasing in alpha power, theta/beta, alpha/beta, (theta + alpha)/beta, (theta + alpha)/(alpha + beta) and increasing in the theta power and the gamma power. Furthermore, several interactions among independent variables had significant effects on the EEG responses.. The EEG implementation for the investigation of neural responses to physical demands allows for the possibility of newer nontraditional and faster methods of human performance monitoring. These methods provide effective and reliable results as compared to other traditional methods. This study will safeguard the physical capabilities and possible health risks of industrial workers. And the applications of these tasks can occur in almost all working environments (factories, warehouses, airports, building sites, farms, hospitals, offices, etc.) that are at high altitudes. It can include lifting boxes at a packaging line, handling construction materials, handling patients in hospitals, and cleaning.

Topics: Action Potentials; Adolescent; Adult; Aged; Alanine Transaminase; Analgesics; Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Apoptosis; Arrhythmias, Cardiac; Atrial Fibrillation; Biological Transport; Biomarkers; Blood Gas Analysis; Blood-Brain Barrier; Blotting, Western; Bone and Bones; Bone Marrow; Bone Neoplasms; Brain; Breast Neoplasms; Calcium; Carbon Tetrachloride; Cartilage, Articular; Case-Control Studies; CD59 Antigens; CDC2 Protein Kinase; Celastrus; Cell Cycle; Cell Division; Cell Line; Cell Line, Tumor; Cell Proliferation; Cell Survival; Chemical Fractionation; Colitis, Ulcerative; Colon; Computer Simulation; Curcumin; Cyclin B1; Cymenes; Cytokines; Dextran Sulfate; Dipeptidyl Peptidase 4; Disease Models, Animal; Disease Progression; Dose-Response Relationship, Drug; Ectodysplasins; Electroencephalography; Endothelial Cells; Epithelial Cells; Epithelial-Mesenchymal Transition; Exosomes; Female; Flavonoids; G2 Phase; Gene Expression Regulation; Glial Cell Line-Derived Neurotrophic Factor; Heart Atria; Heart Conduction System; Heart Ventricles; HeLa Cells; Hemodynamics; Humans; Image Interpretation, Computer-Assisted; Indoles; Inflammation; Interleukin-1beta; Interleukin-6; Iridoid Glycosides; Ki-1 Antigen; Lens, Crystalline; Lifting; Liver; Liver Cirrhosis; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Inbred ICR; Microelectrodes; Middle Aged; Models, Cardiovascular; Multiparametric Magnetic Resonance Imaging; Myeloid Differentiation Factor 88; NADPH Oxidase 1; Neoplasm Grading; NF-kappa B; Osteoarthritis; Osteoblasts; Osteoclasts; Oxidative Stress; Oxygen; Patch-Clamp Techniques; PC-3 Cells; Permeability; Peroxidase; Plant Extracts; Plant Leaves; Prostate; Prostatic Neoplasms; Protective Agents; Proto-Oncogene Proteins c-akt; Psychophysics; Purpura, Thrombocytopenic, Idiopathic; Rabbits; Rats; Rats, Sprague-Dawley; Recovery of Function; Retrospective Studies; RNA, Long Noncoding; ROC Curve; Safety; Shoes; Signal Transduction; Sodium; Sonication; Spinal Cord; Spinal Cord Injuries; Syringa; Tight Junctions; Tissue Inhibitor of Metalloproteinase-1; Toll-Like Receptor 2; Transforming Growth Factor beta2; Transient Receptor Potential Channels; Tumor Microenvironment; Tumor Necrosis Factor-alpha; Umbilical Cord; Up-Regulation; Ventricular Function; Young Adult

Nonalcoholic steatohepatitis (NASH) is the advanced form of nonalcoholic fatty liver disease, which is often accompanied by obese and/or type II diabetes mellitus. Approximately one-third of NASH patients develop hepatic fibrosis. Hepatic stellate cells are the major effector cells during liver fibrogenesis. Advanced liver fibrosis usually proceeds to cirrhosis and even hepatocellular carcinoma, leading to liver failure, portal hypertension and even death. Currently, there are no approved agents for treatment and prevention of liver fibrosis in human beings. Curcumin, the principal curcuminoid of turmeric, has been reported to show antitumor, antioxidant, and anti-inflammatory properties both in in vitro and in vivo systems. Accumulating data shows that curcumin plays a critical role in combating liver fibrogenesis. This review will discuss the inhibitory roles of curcumin and update the underlying mechanisms by which curcumin targets in inhibiting hepatic stellate cell activation.

Topics: Animals; Curcumin; Diabetes Mellitus, Type 2; Disease Models, Animal; Hepatic Stellate Cells; Humans; In Vitro Techniques; Leptin; Lipid Metabolism; Liver Cirrhosis; Oxidative Stress; Signal Transduction

Topics: Animals; Curcumin; Humans; Liver Cirrhosis

Since 1900 bc, several therapeutic activities have been attributed to the rhizomes of the plant Curcuma longa for a variety of diseases, including liver disorders. Curcumin, the main active compound obtained from this plant, was first isolated two centuries ago and its structure as diferuloylmethane was determined in 1910. Curcumin has shown anti-inflammatory, anti-oxidant, antifungal, antibacterial and anticancer activities. The pharmacological properties of curcumin were reviewed recently and focused mainly on its anticancer properties. However, its beneficial activity on liver diseases (known centuries ago, and demonstrated recently utilizing animal models) has not being reviewed in depth until now. The curcumin ability to inhibit several factors like nuclear factor-kappaB, which modulates several pro-inflammatory and profibrotic cytokines as well as its anti-oxidant properties, provide a rational molecular basis to use it in hepatic disorders. Curcumin attenuates liver injury induced by ethanol, thioacetamide, iron overdose, cholestasis and acute, subchronic and chronic carbon tetrachloride (CCl(4)) intoxication; moreover, it reverses CCl(4) cirrhosis to some extent. Unfortunately, the number of studies of curcumin on liver diseases is still very low and investigations in this area must be encouraged because hepatic disorders constitute one of the main causes of worldwide mortality.

Topics: Animals; Carbon Tetrachloride; Cholestasis; Curcuma; Curcumin; Humans; Iron; Liver; Liver Cirrhosis; Liver Cirrhosis, Biliary; Liver Diseases; Thioacetamide

Liver fibrosis and its end-stage disease cirrhosis are major world health problems arising from chronic injury of the liver by a variety of etiological factors including viruses, alcohol and drug abuse, the metabolic syndrome, autoimmune disease and hereditary disorders of metabolism. Fibrosis is a progressive pathological process in which wound-healing myofibroblasts of the liver respond to injury by promoting replacement of the normal hepatic tissue with a scar-like matrix composed of cross-linked collagen. Until recently it was believed that this process was irreversible. However emerging experimental and clinical evidence is starting to show that even cirrhosis is potentially reversible. Key to this is the discovery that reversion of fibrosis is accompanied by clearance of hepatic stellate cells (HSC) by apoptosis. Furthermore, proof-of-concept studies in rodents have demonstrated that experimental augmentation of HSC apoptosis will promote the resolution of fibrosis. Consequently there is now considerable interest in determining the molecular events that regulate HSC apoptosis and the discovery of drugs that will stimulate HSC apoptosis in a selective manner. This review will consider the regulatory role played by growth factors (e.g. NGF, IGF-1, TGFbeta), death receptor ligands (TRAIL, FAS), components and regulators of extracellular matrix (integrins, collagen, matrix metalloproteinases and their tissue inhibitors) and signal transduction proteins and transcription factors (Rho/Rho kinase, Jun N-terminal Kinase (JNK), IkappaKinase (IKK), NF-kappa B). The potential for known pharmacological agents such as gliotoxin, sulfasalazine, benzodiazepine ligands, curcumin and tanshinone I to induce HSC apoptosis and therefore to be used therapeutically will be explored.

Topics: Animals; Apoptosis; Curcumin; Extracellular Matrix; Gliotoxin; Growth Substances; Humans; Liver; Liver Cirrhosis; Macrophages; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 3; N-Methyl-3,4-methylenedioxyamphetamine; NF-kappa B; Sirolimus

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; 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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; 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Recent reports indicated that curcumin had beneficial effects in animal models of liver injury and cirrhosis. Current study aimed to investigate the effects of curcumin supplementation in patients with liver cirrhosis. In this randomized double-blind placebo-controlled trial, 70 patients with liver cirrhosis aged 20-70 years were randomly divided into two groups to receive 1,000 mg/day curcumin (n = 35) or placebo (n = 35) for 3 months. Model for end-stage liver disease (MELD) (i), MELD, MELD-Na, and Child-Pugh scores were used to assess the severity of cirrhosis. Sixty patients (29 in the curcumin group and 31 in the placebo group) completed the study. MELD(i) (15.55 ± 3.78 to 12.41 ± 3.07), MELD (15.31 ± 3.07 to 12.03 ± 2.79), MELD-Na (15.97 ± 4.02 to 13.55 ± 3.51), and Child-Pugh (7.17 ± 1.54 to 6.72 ± 1.31) scores decreased significantly in the curcumin group after 3-month intervention (p < .001, p < .001, p = .001, and p = .051, respectively), whereas they increased significantly in the placebo group (p < .001, p < .001, p < .001, p = .001, respectively). Significant differences were only observed between the two groups in MELD(i), MELD, MELD-Na, and Child-Pugh scores after 3-month intervention (p < .001 for all of them). In this pilot study, beneficial effects of curcumin supplementation were observed in decreasing disease activity scores and severity of cirrhosis in patients with cirrhosis.

Topics: Adult; Aged; Curcumin; Dietary Supplements; Double-Blind Method; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Pilot Projects; Retrospective Studies; Young Adult

Current study aimed to find the effects of curcumin on quality of life (QoL) in liver cirrhotic patients.. In this randomized double-masked placebo-controlled trial, 70 cases with liver cirrhosis aged 20-70 years were randomly divided into two groups to receive 1000 mg/day curcumin (n = 35) or placebo (n = 35) for 12 weeks. The health-related QoL (HRQoL) was assessed by CLDQ, LDSI 2.0, and SF-36.. Fifty-eight patients (28 in curcumin and 30 in placebo groups) finished the research. Compared with baseline, overall scores as well as most of CLDQ domains (e.g. Fatigue, Emotional Function, Worry, Abdominal Symptoms, and Systemic Symptoms) and the Physical and Mental health (Total) scores and most of SF-36 domains (e.g. Physical Functioning, Bodily Pain, Vitality, Social Functioning, and Mental Health) increased considerably (P < 0.05) after curcumin administration. Furthermore, curcumin reduced most of LDSI 2.0 domains (e.g. Itch, Joint pain, Pain in the right upper abdomen, Sleeping during the day, Decreased appetite, Depression, Fear of complication, Jaundice, Hindrance in Financial Affairs, Change in use of time, Decreased sexual interest, and Decreased sexual activity) significantly (P < 0.05). Significant differences were noticed between two groups in CLDQ domains and overall scores, LDSI 2.0 domains and overall scores, SF-36 Physical and Mental health (total) scores and all its domains scores (P < 0.05), adjusting for baseline values and disease duration.. Curcumin improved QoL in liver cirrhotic patients according to CLDQ, LDSI 2.0, and SF-36 domains. Additional studies are warranted to consider curcumin as a safe, accessible, and low-cost complementary therapeutic option in cirrhosis.

Topics: Adult; Aged; Curcumin; Double-Blind Method; Female; Humans; Liver Cirrhosis; Male; Middle Aged; Quality of Life; Surveys and Questionnaires

Nonalcoholic fatty liver disease (NAFLD) is a major global health problem. The most common cause of death in these patients is due to cardiovascular disorders. The aim of this study was to examine the effects of curcumin supplementation on cardiovascular risk factors in patients with NAFLD.. In this randomized, placebo-controlled, clinical trial, fifty two patients with NAFLD were randomly assigned to receive life style recommendations plus either 1500 mg curcumin or placebo for 12 weeks. Anthropometric indices, blood lipid profile, insulin resistance, as well as hepatic steatosis and fibrosis scores were measured at the beginning and the end of the study, and compared between and within groups.. Hepatic fibrosis, serum cholesterol, glucose and alanin aminotransferase (ALT) reduced significantly only in curcumin group (p < 0.05). Anthropometric indices, blood lipid profile, insulin resistance, and hepatic steatosis decreased significantly in both groups (p < 0.05), without any significant difference between two groups.. Our results showed that daily intake of 1500 mg curcumin plus weight loss is not superior to weight loss alone in amelioration of cardiovascular risk factors in patients with NAFLD. Further studies with different dosages of curcumin are needed to be able to conclude about the effects of this dietary supplement on cardiovascular risk factors and NAFLD characteristics.

Topics: Anti-Inflammatory Agents, Non-Steroidal; Blood Glucose; Curcumin; Dietary Supplements; Double-Blind Method; Female; Homeostasis; Humans; Insulin Resistance; Iran; Lipids; Liver; Liver Cirrhosis; Male; Middle Aged; Non-alcoholic Fatty Liver Disease

Curcumin 2005-8 (Cur5-8), a derivative of curcumin, improves fatty liver disease via AMP-activated protein kinase activation and autophagy regulation. EW-7197 (vactosertib) is a small molecule inhibitor of transforming growth factor β (TGF-β) receptor I and may scavenge reactive oxygen species and ameliorate fibrosis through the SMAD2/3 canonical pathway. This study aimed to determine whether co-administering these two drugs having different mechanisms is beneficial.. Hepatocellular fibrosis was induced in mouse hepatocytes (alpha mouse liver 12 [AML12]) and human hepatic stellate cells (LX-2) using TGF-β (2 ng/mL). The cells were then treated with Cur5-8 (1 μM), EW-7197 (0.5 μM), or both. In animal experiments were also conducted during which, methionine-choline deficient diet, Cur5-8 (100 mg/kg), and EW-7197 (20 mg/kg) were administered orally to 8-week-old C57BL/6J mice for 6 weeks.. TGF-β-induced cell morphological changes were improved by EW-7197, and lipid accumulation was restored on the administration of EW-7197 in combination with Cur5-8. In a nonalcoholic steatohepatitis (NASH)-induced mouse model, 6 weeks of EW-7197 and Cur5-8 co-administration alleviated liver fibrosis and improved the nonalcoholic fatty liver disease (NAFLD) activity score.. Co-administering Cur5-8 and EW-7197 to NASH-induced mice and fibrotic hepatocytes reduced liver fibrosis and steatohepatitis while maintaining the advantages of both drugs. This is the first study to show the effect of the drug combination against NASH and NAFLD. Similar effects in other animal models will confirm its potential as a new therapeutic agent.

Topics: Animals; Curcumin; Fibrosis; Humans; Liver Cirrhosis; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Transforming Growth Factor beta; Transforming Growth Factors

The purpose of this study was to evaluate the effect of curcumin, an active polyphenol, on the leptin induced lowering of miR-122 in Hepatic stellate cells (HSCs) in vivo and an animal model. Gene expression was evaluated by transfection assay, real-time PCR, or Western blot analysis. The liver fibrosis model of leptin deficient mouse was used for in vivo experiment. As a result, curcumin showed inhibitory effect on leptin induced lowering of the miR-122 in HSCs. Curcumin suppressed leptin induced sonic hedgehog (Shh) expression and blocked leptin induced Shh signaling pathway, which was essential for curcumin inhibition of the negative role of leptin in miR-122 expression in HSCs. The influence of curcumin on the negative effect of leptin on miR-122 level was followed by the attenuation of liver fibrosis caused by leptin in leptin-deficient mouse model. In conclusion, curcumin could reduce the decrease of miR-122 level in HSCs induced by leptin and inhibit liver fibrosis induced by leptin. These data may have potential implications to treat with liver fibrosis by elevating the expression of leptin in humans especially obese patients.

Topics: Animals; Curcumin; Disease Models, Animal; Hedgehog Proteins; Hepatic Stellate Cells; Humans; Leptin; Liver Cirrhosis; Mice; MicroRNAs

Curcumin, a kind of natural compound, has been previously proven to inhibit the autophagy in hepatic stellate cells (HSCs) and induce their apoptosis. However, it is not clear whether the enhanced apoptosis of activated HSCs (aHSCs) caused by curcumin depends on autophagy inhibition. We aim to verify this hypothesis and explore the potential mechanisms in this study. Immortalized human HSC line LX-2 was used as an experimental specimen and pretreated with transforming growth factor β1(TGF-β1) for 24 h to activate it before drug application. The levels of autophagy, apoptosis, cell activity, lipid metabolism, and the activity of the PI3K/Akt/mTOR signal pathway were evaluated by multiple methods, such as Western blotting, mcherry-EGFP-LC3B adenoviruses transfection, immunofluorescence, Nile Red staining, flow cytometry among others. Our results showed that rapamycin, an autophagy activator, could partly offset the effects of curcumin on autophagy and apoptosis of LX-2 cells, while 3-Methyladenine (3-MA), an autophagy inhibitor, could enhance these effects. Furthermore, curcumin could promote the activity of the PI3K/Akt/mTOR signal pathway in LX-2 cells, while PI3K inhibitor could partly offset this effect and increase the autophagy level. Overall, we demonstrated that curcumin could inhibit the activity and promote LX-2 cells apoptosis by suppressing autophagy by activating the PI3K/Akt/mTOR signal pathway. In addition, lipid recovery and energy deprivation due to autophagy inhibition may be the exact mechanism by which curcumin attenuates the pro-fibrotic activity of LX-2.

Topics: Apoptosis; Autophagy; Curcumin; Hepatic Stellate Cells; Humans; Liver Cirrhosis; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; TOR Serine-Threonine Kinases

In this study, the fraction extracted from turmeric powder with 50% ethanol and fractionated with n-hexane were administered to diet-induced NASH model rats. NASH model was prepared with SD rats by feeding an originally designed choline-deficient, high-fat, high-fructose (HFF-CD) diet for 10 weeks. To the HFF-CD diet, hexane fraction and 50% ethanol fraction after hexane fractionation were added at 100 mg/kg body weight. 10 weeks later, blood samples and liver were collected for the following parameters: lipid weights, serum ALT, AST, TG, liver TG, TBARS levels, lipid metabolism-related gene expression and histopathological examination of the liver. As the results, the hexane fraction and 50% ethanol fraction showed a decrease in lipid weight, a decrease in hepatic TG, and activation of PPAR-α in the lipid metabolism-related gene test. These results suggest that the hexane fraction of turmeric has an inhibitory effect on fat accumulation in the liver by promoting lipid metabolism in NASH model rats.

Topics: Animals; Curcuma; Diet, High-Fat; Ethanol; Hexanes; Lipid Metabolism; Lipids; Liver; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Rats; Rats, Sprague-Dawley

Background: Liver cirrhosis is a life-threatening seqsuel of many chronic liver disorders of varying etiologies. In this study, we investigated protein targets of curcumin in liver cirrhosis based on a bioinformatics approach. Methods: Gene/protein associations with curcumin and liver cirrhosis were probed in drug−gene and gene−diseases databases including STITCH/DGIdb/DisGeNET/OMIM/DISEASES/CTD/Pharos and SwissTargetPrediction. Critical clustering groups (MCODE), hub candidates and critical hub genes in liver cirrhosis were identified, and connections between curcumin and liver cirrhosis-related genes were analyzed via Venn diagram. Interaction of hub genes with curcumin by molecular docking using PyRx-virtual screening tools was performed. Results: MCODE analysis indicated three MCODEs; the cluster (MCODE 1) comprised 79 nodes and 881 edges (score: 22.59). Curcumin database interactions recognized 318 protein targets. Liver cirrhosis genes and curcumin protein targets analysis demonstrated 96 shared proteins, suggesting that curcumin may influence 20 candidate and 13 hub genes, covering 81% of liver cirrhosis critical genes and proteins. Thirteen shared proteins affected oxidative stress regulation, RNA, telomerase activity, cell proliferation, and cell death. Molecular docking analysis showed the affinity of curcumin binding hub genes (Binding affinity: ΔG < −4.9 kcal/mol). Conclusions: Curcumin impacted on several critical liver cirrhosis genes mainly involved in extracellular matrix communication, focal adhesion, and the response to oxidative stress.

Topics: Curcumin; Humans; Liver Cirrhosis; Molecular Docking Simulation; RNA; Telomerase

Topics: Animals; Chitosan; Curcumin; Liver Cirrhosis; Metal Nanoparticles; Mice; Molecular Docking Simulation; Nanoparticles; Receptor, Platelet-Derived Growth Factor beta; Silver; Tissue Distribution; Tissue Inhibitor of Metalloproteinase-1; Toll-Like Receptor 9

Obese patients are often accompanied by hyperleptinemia and prone to develop liver fibrosis. Accumulating data including those obtained from human studies suggested the promotion role of leptin in liver fibrosis. The remodeling of the DNA methylation is an epigenetic mechanism for regulating gene expression and is essential for hepatic stellate cell (HSC) activation, a key step in liver fibrogenesis. Leptin increases the expression of methionine adenosyltransferase 2A (MAT2A) which is associated with DNA methylation and HSC activation. Curcumin, an active polyphenol of the golden spice turmeric, inhibits leptin-induced HSC activation and liver fibrogenesis. Thus, the present research aimed to investigate the influence of curcumin on the roles of leptin in MAT2A expression in HSCs.. The in vivo experiments were conducted by using leptin-deficient obese mice. The gene expressions were examined by Western blot, real-time PCR, promoter activity assay, and immunostaining analysis.. Curcumin reduced leptin-induced MAT2A expression. JNK signaling contributed to leptin-induced increase in MAT2A level, which could be interrupted by curcumin treatment. Curcumin inhibited leptin-induced MAT2A promoter activity by influencing MAT2A promoter fragments between -2,847 bp and - 2,752 bp and between -2,752 bp and +49 bp. The effect of curcumin on leptin-induced MAT2A expression paralleled the reductions in leptin-induced activated HSCs and liver fibrosis.. These results might have implications for curcumin inhibition of the liver fibrogenesis in obese patients with hyperleptinemia.

Topics: Animals; Curcumin; Hepatic Stellate Cells; Leptin; Liver Cirrhosis; Male; MAP Kinase Signaling System; Methionine Adenosyltransferase; Mice; Mice, Inbred C57BL; Mice, Obese; Obesity

Liver fibrosis, caused by multiple chronic liver injuries, is a known contributor to cirrhosis and even liver cancer. As a Traditional Chinese Medicine (TCM), Rhizoma curcumae has been extensively used in the treatment of liver fibrosis with satisfying therapeutic effects; however, its mechanism is unclear. The essential oil is the main bioactive component. The purpose of this study was to investigate the chemical profile and the pharmacological mechanisms of the essential oil of Rhizoma curcumae (EORC) against liver fibrosis by combining network pharmacology and transcriptomic technologies. A total of 37 active compounds were identified using the GC/MS system and literature mining, and the corresponding putative targets were predicted. Then, network pharmacology method was applied to identify the 168 candidate targets of EORC-alleviated liver fibrosis. String database and Cytoscape software were used to build the herb-compound-target network and protein-protein interactions (PPIs) network. Functional and pathway enrichment analysis indicated that EORC significantly influenced TGF-β1/Smads and PI3K/AKT pathways. Experimentally, we verified that EORC attenuated the severity and pathological changes during liver fibrosis progression based on the CCl4-induced liver fibrosis rat model. Transcriptomic technologies demonstrated that EORC ameliorated liver fibrosis partially by regulating the TGF-β1/Smads and PI3K/AKT pathways. In addition, the effect of vinegar-processed EORC was more significant than that of the raw one. Therefore, EORC can alleviate the severity of liver fibrosis through mechanisms predicted by network pharmacology and provide a basis for the further understanding of the application of EORC in the treatment of liver fibrosis.

Topics: Acetic Acid; Animals; Body Weight; Collagen; Curcuma; Drugs, Chinese Herbal; Liver; Liver Cirrhosis; Male; Oils, Volatile; Phosphatidylinositol 3-Kinase; Plant Oils; Protein Interaction Maps; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Rhizome; Signal Transduction; Smad Proteins; Transforming Growth Factor beta1

Curcumin is described as an antioxidant, hepato-protective and antifibrotic in liver fibrosis, although its mechanism is still not known. One of the models of the chronic liver disease stemming from oxidative stress and the generation of free radical has been considered to be bile duct ligation (BDL). Paraoxonase 1 (PON1) is a prominent antioxidant enzyme. Therefore, the objective of the present research is to assess the effects of curcumin on upregulation of PON1 in BDL rats.. As predicted, the rats have been divided into the four groups of Sham, Sham + Cur (curcumin), BDL and BDL + Cur. We evaluated the efficacy of curcumin (100 mg/kg/day) on protein and gene expression of PON1 and regulatory genes contributed to the gene expression PON1 such as Sp1, PKC. Curcumin attenuated alterations in liver histology, hepatic enzymes and the mRNA expression of fibrotic markers (p<0.05). In addition, curcumin increased significantly mRNA, protein expression of PON1 and mRNA of the genes that are contributed to the expression of PON1 such as Sp1, PKC. Cirrhosis progression may be inhibited by treatment with curcumin through the increased influence the expression and activity of PON1.

Topics: Animals; Antioxidants; Apolipoprotein A-I; Aryldialkylphosphatase; Bile Ducts; Curcumin; Genes, Regulator; Ligation; Liver; Liver Cirrhosis; Oxidative Stress; Protective Agents; Protein Kinase C-alpha; Rats; Rats, Wistar; RNA, Messenger; Sterol Regulatory Element Binding Protein 1

Cirrhosis is a chronic liver disease. The present work aimed to evaluate the regulatory immune effect of curcumin in hepatic cirrhosis induced by carbon tetrachloride (CCl4) injections in experimental rats' model. Chronic liver fibrosis was induced in experiment animals by recurrent injections of CCl4 for more than 5 weeks. They were divided into five groups: first group was injected with normal saline, second group with CCl4, third, fourth, and fifth groups were injected with CCl4 (intraperitoneal injection) at dose 3 ml/kg, two times weekly for 6 weeks supplemented with the administration of curcumin with concentrations 250, 200, and 150 mg/kg. Immune response was analyzed to different treatments. Interleukin 10 (IL-10), pro-inflammatory cytokines TNF-α, TGF-1β, and liver histopathological examinations were conducted. The results showed that estimations of IL-10 concentrations were significantly increased in curcumin groups compared with CCl4 group, whereas TNF-α and TGF-1β levels were significantly decreased comparing with CCl4 group. The histopathological examinations for liver tissues showed that curcumin treated groups have almost retained the normal structure of liver tissues. In conclusion, curcumin inhibited hepatic fibrosis and liver fibrogenesis with regulation of the immune system mechanism against invader chemical toxicity. PRACTICAL APPLICATIONS: Curcumin is well documented for its medicinal properties, commonly used as a spice. Our work has thus demonstrated its effectiveness as an immunomodulatory agent. Practically, clinical studies have suggested that curcumin displays a diverse and powerful array of pharmacological effects in nearly all of the human body's major organ systems. These are: antidiabetes, anti-inflammatory, anticancer, antiaging, antioxidant, antibacterial infection, hepatoprotective, neurodegenerative, and cardiovascular effects.

Topics: Animals; Carbon Tetrachloride; Curcumin; Immunity; Liver Cirrhosis; Rats

The massive production and activation of myofibroblasts (MFB) is key to the development of liver fibrosis. In many studies, it has been proven that hepatocytes are an important part of MFB, and can be transformed into MFB through epithelial-mesenchymal transition (EMT) during hepatic fibrogenesis. In our previous study, we confirmed that curcumin inhibited EMT procession and differentiation of hepatocytes into MFB. In addition, in previous studies, it has been shown that autophagy plays an important role in the regulation of cellular EMT procession. In the current study, we showed that curcumin inhibited TGF-β/Smad signaling transmission by activating autophagy, thereby inhibiting EMT. The mechanism of degradative polyubiquitylation of Smad2 and Smad3 is likely through inhibiting tetratricopeptide repeat domain 3 (TTC3) and by inducing ubiquitylation and proteasomal degradation of Smad ubiquitination regulatory factor 2 (SMURF2), which on account of the increase of autophagy in hepatocytes. Curcumin inhibits levels of reactive oxygen species (ROS) and oxidative stress in hepatocytes by activating PPAR-α, and regulates upstream signaling pathways of autophagy AMPK and PI3K/AKT/mTOR, leading to an increase of the autophagic flow in hepatocytes. In this study, we confirm that curcumin effectively reduced the occurrence of EMT in hepatocytes and inhibited production of the extracellular matrix (ECM) by activating autophagy, which provides a potential novel therapeutic strategy for hepatic fibrosis.

Topics: Autophagy; Curcumin; Epithelial-Mesenchymal Transition; Hepatocytes; Humans; Liver Cirrhosis; Oxidative Stress; Phosphatidylinositol 3-Kinases; Transforming Growth Factor beta1

The active polyphenol curcumin demonstrates therapeutic effects against various different diseases. Researches revealed the inhibitory roles of curcumin in hepatic stellate cell (HSC) activation and fibrogenesis. HSC activation, a key step in liver fibrogenesis, requires the remodeling of DNA methylation, which is associated with methionine adenosyltransferase II (MATII) composed of catalytic subunit MAT2A and regulatory subunit MAT2B. MATII is essential for HSC activation in vitro. The present researches aimed to investigate the effect of curcumin on MAT2B expression in HSCs in vivo and in vitro. Results demonstrated that curcumin could reduce MAT2B expression in HSCs at multiple levels. The activation of p38 MAPK pathway promoted MAT2B expression in HSCs. The effect of curcumin on MAT2B was through its interruption of p38 MAPK signaling pathway. Knockdown of MAT2B inhibited HSC activation and reduced collagen level in the model of liver fibrosis. Curcumin down-regulation of MAT2B contributed to the inhibitory role of curcumin on HSC activation and collagen expression in mouse livers. This study provided evidences for the effect of curcumin on the expression of MAT2B, an enzyme for the biosynthesis of methyl donor S-adenosylmethionine, in HSCs and demonstrated the function significance of curcumin-induced downregulation of MAT2B in curcumin inhibition of liver fibrosis.

Topics: Animals; Collagen; Curcumin; Down-Regulation; Gene Knockdown Techniques; Hepatic Stellate Cells; Liver Cirrhosis; Male; Methionine Adenosyltransferase; Mice; Mice, Inbred C57BL; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Rats; Rats, Sprague-Dawley; S-Adenosylmethionine; Signal Transduction

Bisphenol A (BPA) has been shown to induce liver fibrosis in rodents. Therefore, this study examined the protective effect of a triple combination of curcumin (Cur), N-acetyl cysteine (NAC) and propolis (Prp) extract against BPA-induced hepatic fibrosis.. 100 Wistar male rats were equally assigned into 10 groups; one group was designated as control. 10 rats were gavaged with BPA (50 mg/kg/day) for 8 wk and left un-treated (BPA group). The remaining 80 rats were divided into 8 groups, distributed in 2 models. Protective model: rats were daily co-treated with BPA and Cur (100 mg/kg, p.o) or NAC (150 mg/kg, p.o) or Prp (200 mg/kg, p.o) or their combination for 8 wk. Preventive model: rats were daily treated with Cur or NAC or Prp or their combination for 4 wk before BPA administration and then in the same manner as protective model.. Current treatment interventions significantly alleviated BPA-induced hepatic damage and fibrosis. They also restored pro-oxidant/antioxidant balance, shifted cytokine balance towards the anti-inflammatory side, decreasing interleukin-1β/interleukin-10 ratio. Moreover, these compounds seem to exert anti-apoptotic effects by increasing the immunoexpression of B-cell lymphoma 2 in hepatocytes and decreasing hepatic caspase-3 content. Finally, they ameliorated extracellular matrix turn over through down-regulation of matrix metalloproteinase-9 and up-regulation of tissue inhibitor of matrix metalloproteinase-2 genetic expression.. Current treatments guarded against BPA-induced hepatic fibrosis due to their antioxidant, anti-inflammatory and anti-apoptotic properties, decreasing extracellular matrix turnover. Interestingly, the triple therapy provided hepatoprotection superior to monotherapy. Besides, prophylactic and concurrent treatments seem to be more effective than concurrent treatments.

Topics: Acetylcysteine; Animals; Apoptosis; Benzhydryl Compounds; Chemical and Drug Induced Liver Injury; Curcumin; Drug Therapy, Combination; Inflammation; Interleukins; Liver; Liver Cirrhosis; Male; Phenols; Propolis; Rats; Rats, Wistar

Liver fibrosis is an inflammatory and fibrogenic process that occurs following chronic liver damage. TGFβ1 is the key inducer of fibrosis. MiR-21 and miR-122 are two miRNAs that their expression changes during fibrosis. In the present study, we investigate the effects of curcumin, quercetin, and atorvastatin on the expression levels of miR-21 and miR-122 and evaluated their correlation with TGFβ1 expression in bile duct ligation (BDL)-induced fibrotic rats.. Thirty two adult male Wistar rats were divided into 8 groups (n = 8 for each): Sham, Sham + curcumin (100 mg/kg/day), Sham + quercetin (30 mg/kg/day), Sham + atorvastatin (15 mg/kg/day), BDL, BDL + curcumin, BDL + quercetin, BDL + atorvastatin and treated for four weeks via oral gavage. The expression of miR-21, miR-122, and TGFβ1 was evaluated via RT-qPCR.. The expression levels of TGFβ1 and miR-21 were significantly increased in the BDL group compared to the Sham group (P < 0.05), but the expression of miR-122 was significantly decreased in the BDL group compared to the Sham group (P < 0.05). Curcumin, quercetin, and atorvastatin treatment lead to down-regulation of miR-21 and TGFβ1 and up-regulation of miR-122 in the BDL groups. There was no significant difference between these drugs in altering gene expression and all had the same effects. Moreover, a direct significant correlation was observed between mir-21 and TGFβ1 and an inverse significant correlation between mir-122 and TGFβ1 expression.. In summary, targeting these molecular pathways may partially prevent the progression of liver fibrosis.

Topics: Animals; Atorvastatin; Curcumin; Gene Expression; Liver; Liver Cirrhosis; Male; MicroRNAs; Quercetin; Rats; Rats, Wistar; Real-Time Polymerase Chain Reaction; Transforming Growth Factor beta1

Hepatic fibrosis is a public health problem characterized by activation of hepatic stellate cells (HSCs), which triggers excessive production of extracellular matrix (ECM). Inhibition of HSC activation may be an effective treatment. Since various pathways control HSC activation, a combination of drugs with different mechanisms may be more effective than monotherapy.. Here, we prepared liposomes loaded with curcumin and cyclopamine to inhibit HSC activation. We systematically analyzed the physicochemical characteristics of liposomes loaded with the two drugs, as well as their effects on HSC proliferation, activation and collagen production on gene, protein and cellular levels.. The prepared liposomes helped solubilize both drugs, contributing to their uptake by cells. Liposomes loaded with both drugs inhibited cell proliferation, migration and invasion, as well as induced more apoptosis and perturbed the cell cycle more than the free combination of both drugs in solution or liposomes loaded with either drug alone. Liposomes loaded with both drugs strongly suppressed HSC activation and collagen secretion.. Our results suggest that liposome encapsulation can increase the uptake of curcumin and cyclopamine as well as the synergism between them in anti-fibrosis. This approach shows potential for treating hepatic fibrosis.

Topics: Animals; Apoptosis; Cell Proliferation; Cells, Cultured; Collagen; Curcumin; Liposomes; Liver Cirrhosis; Rats; Veratrum Alkaloids

The present research work was designed to evaluate the effects of curcumin supplementation on various biochemical parameters in rats with thioacetamide (TAA) induced liver cirrhosis. For this purpose 24 male Albino Wistar rats were randomly distributed into four groups (n=6).Group I served as control, Group II and Group III received thioacetamide 200mg/kg b.w, i.p, twice a week for 12 weeks in first phase. In second phase Group II received saline and Group III received curcumin 50mg/kg b.w/day, i.p for 12 weeks, in second phase, Group IV received curcumin 50mg/kg b.w/day, i.p, for 12 weeks, in first phase and saline in second phase. Evaluation of histopathological and biochemical parameters was carried out by liver histopathology and estimation of total and direct bilirubin, liver specific enzymes, antioxidant enzymes, MDA level, plasma and intraerythrocyte sodium and potassium respectively. Histopathology of liver showed highest degree of fibrosis and nodule formation, significant alteration in biochemical parameters indicated development of severe liver cirrhosis. Curcumin treatment showed reduced amount of fibrosis and significant reduction in level of liver biomarkers, reversal of antioxidant enzymes (SOD and GSH), MDA level, catalase activity and regain of electrolyte homeostasis. These findings confirm the protective role of curcumin in liver cirrhosis.

Topics: Animals; Antioxidants; Biomarkers; Curcumin; Homeostasis; Liver; Liver Cirrhosis; Male; Oxidative Stress; Protective Agents; Rats; Rats, Wistar; Thioacetamide

Curcuma wenyujin Y.H. (CW), a variety of Curumae Rhizoma, which documented in China Pharmacopeia, has long been used as plant medicine for its traditional effect on promoting Qi, activating blood stagnation and expelling blood stasis. Nowadays, it is often used in clinic for extraordinary effect on liver diseases. It is worthy to be noted that CW processed with vinegar has been applied in clinic for 1500 years which started in the northern and southern dynasties.. Liver fibrosis is a worldwide clinical issue. It is worth developing a multi-target and multicellular approach which is high efficiency and low side effects for the treatment of hepatic fibrosis. The anti-hepatic fibrosis molecular mechanisms of CW and vinegar Curcuma wenyujin (VCW) need to be explored and elucidated. Furthermore, the study aimed to discuss the efficiency and mechanism differences between CW and VCW in hepatic fibrosis.. Biochemical assays and histopathology were adopted to evaluate the anti-hepatic fibrosis effect of CW and VCW. The TGF-β/Smad signaling involving TGF-β1, TGF-βRⅠ, TGF-βRⅡ and Smad2, Smad3, Smad7 in fibrosis is examined, which is a critical step towards the evaluation of anti-hepatic fibrosis agents. Meanwhile, the MMP/TIMP balance is a potential therapy target by modulating extracellular matrix, which is also examined. Both CW and VCW inhibit the activation and proliferation of hepatic stellate cells and induce apoptosis via blocking TGF-β/Smad signaling pathways. Additionally, the level of MMP-2/TIMP-1 regulated significantly, which suggest CW and VCW participate in the degradation process, and maintain the formation and production of extracellular matrix.. Raw and vinegar processed Curcuma wenyujin regulates hepatic fibrosis via bloking TGF-β/Smad signaling pathways and up-regulation of MMP-2/TIMP-1 ratio. And VCW has more exhibition than CW.

Topics: Acetic Acid; Animals; Cell Line; Curcuma; Liver; Liver Cirrhosis; Male; Matrix Metalloproteinase 2; Plant Extracts; Rats, Sprague-Dawley; Signal Transduction; Smad2 Protein; Smad3 Protein; Tissue Inhibitor of Metalloproteinase-1; Transforming Growth Factor beta1

To investigate the protective effects of curcumin on bile duct ligation(BDL)-induced liver cholestasis in mice, so as to provide a new treatment strategy for liver fibrosis.. Forty-two healthy adult male BALB/c mice were randomly divided into sham group (n =6), sham+curcumin group (n=6), BDL treatment group (n=10), BDL+curcumin group(n=10), BDL+curcumin+ZnPP group (n=10). Seven days after BDL operation, the sham operation + curcumin group and the BDL+ curcumin group were treated with curcumin at the dose of 30 mg/kg by intraperitoneal injection once a day for 7 days.The mice in BDL+ curcumin +ZnPP group were treated with curcumin (30 mg/kg) and ZnPP (50 μmol/kg) by intraperitoneal injection once a day for 7 days. For the sham group and the BDL group, mice were treated with equal-volume saline daily by intraperitoneal injection. After 14 days of BDL, the plasma and liver tissues were collected, the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured. The pathological changes of liver tissue and liver fibrosis were observed, and the protein expression of HO-1 in liver tissue was detected.. Compared with the sham group, mice in the BDL group had enlarged liver gallbladder and the serum levels of ALT and AST were increased significantly (P＜0.05). Meanwhile, the results of Sirius red staining and qRT-PCR of pro-fibrosis related genes showed collagen deposition in the liver, and immunohistochemistry of macrophages and neutrophils showed inflammatory cell infiltration in the liver. Compared with the BDL group, the serum levels of ALT and AST in the curcumin treatment group were decreased significantly (P＜0.05), collagen deposition and inflammatory cell infiltration were improved, and HO-1 expression was increased (P＜0.05) after curcumin treatement. In the curcumin treatment group, the protective effect of curcumin on liver injury could be reversed by HO-1 active inhibitor ZnPP.. Curcumin can improve liver inflammation and fibrosis caused by BDL, and this protective effect is related to the regulation of HO-1 activity by curcumin.

Topics: Animals; Cholestasis; Curcumin; Liver; Liver Cirrhosis; Male; Mice; Mice, Inbred BALB C; Treatment Outcome

Platinum and Curcumin conjugation using green chemistry is an attempt to enhance the curcumin effectiveness as an anti-fibrosis. In this study, Platinum and curcumin were conjugated to direct curcumin into the liver. Curcumin platinum nanoparticles (C-PtNPs) were formed by changing curcumin concentration at pH 10. The successful formation of C-PtNPs was recognized with the help of Fourier transform infrared (FTIR) and UV-visible spectrophotometers. The particle size and morphology were studied with the help of dynamic light scattering (DLS) and High-resolution transmission electron microscopy (HR-TEM) respectively. The antimicrobial activity of C-PtNPs, was examined against gram positive and gram negative bacteria. Moreover, the NIH/3 T3 cells were used to test the C-PtNPs activity of modifying initial fibrosis indication. The favorable condition for the synthesis of CPt-NPs was by using curcumin 1.5 mM at pH 10. When compared with free curcumin, C-Pt-NPs exhibited higher activity for decreased production of collagen by NIH/3 T3 cells. Altogether, the formation of C-PtNPs by conjugation of platinum to curcumin is assuring for the curcumin directing to treat the hepatic fibrosis.

Topics: Animals; Anti-Infective Agents; Cell Survival; Curcumin; Gram-Negative Bacteria; Gram-Positive Bacteria; Hydrogen-Ion Concentration; Liver Cirrhosis; Metal Nanoparticles; Mice; Microscopy, Electron, Transmission; NIH 3T3 Cells; Platinum; Spectroscopy, Fourier Transform Infrared

Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic macrophage inflammation, steatosis and fibrosis. Liposomes injected intravenously passively target hepatic myeloid cells and have potential to deliver immunomodulatory compounds and treat disease. We investigated targeting, delivery, immunomodulation and efficacy of liposomes in mice with diet-induced NASH.. Liposome-encapsulated lipophilic curcumin or 1,25-dihydroxy-vitamin D3 (calcitriol) were injected intravenously into mice with diet-induced NASH. Liver and cell liposome uptake was assessed by in vivo imaging and flow cytometry. Immunomodulation of targeted cells were assessed by RNA transcriptome sequencing. NASH was assessed by histological scoring, serum liver enzymes and fasting glucose/insulin and liver RNA transcriptome sequencing.. Liposomes targeted lipid containing MHC class-II. Liposomes are a new strategy to target lipid rich inflammatory dendritic cells and have potential to deliver immunomodulatory compounds to treat NASH.

Topics: Animals; Curcumin; Diet, High-Fat; Disease Progression; Female; Fibrosis; Hepatocytes; Immunologic Factors; Inflammation; Insulin Resistance; Liposomes; Liver; Liver Cirrhosis; Macrophages; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Transcriptome; Vitamin D

Hepatic macrophages have been considered as a therapeutic target for liver fibrosis treatment, and phosphatidylserine (PS)-containing nanoparticles are commonly used to mimic apoptotic cells that can specifically regulate macrophage functions, resulting in anti-inflammatory effects. This study was designed to test the efficacy of PS-modified nanostructured lipid carriers (mNLCs) containing curcumin (Cur) (Cur-mNLCs) in the treatment of liver fibrosis in a rat model. Carbon tetrachloride-induced liver fibrosis in rats was used as an experimental model, and the severity of the disease was examined by both biochemical and histological methods. Here, we showed that mNLCs were spherical nanoparticles with decreased negative zeta potentials due to PS decoration, and significantly increased both mean residence time and area under the curve of Cur. In the rats with liver fibrosis, PS-modification of NLCs enhanced the nanoparticles targeting to the diseased liver, which was evidenced by their highest accumulation in the liver. As compared to all the controls, Cur-mNLCs were significantly more effective at reducing the liver damage and fibrosis, which were indicated by in Cur-mNLCs-treated rats the least increase in liver enzymes and pro-inflammatory cytokines in the circulation, along with the least increase in collagen fibers and alpha smooth muscle actin and the most increased hepatocyte growth factors (HGF) and matrix metalloprotease (MMP) two in the livers. In conclusion, PS-modified NLCs nanoparticles prolonged the retention time of Cur, and enhanced its bioavailability and delivery efficiency to the livers, resulting in reduced liver fibrosis and up-regulating hepatic expression of HGF and MMP-2.

Topics: Animals; Carbon Tetrachloride; Curcumin; Hepatocyte Growth Factor; Liver; Liver Cirrhosis; Macrophages; Male; Matrix Metalloproteinases; Nanoparticles; Nanostructures; Phosphatidylserines; Rats; Rats, Sprague-Dawley

The C-X-C motif chemokine 12/C-X-C chemokine receptor type 4 (CXCL12/ CXCR4) biological axis plays an important role in the pathogenesis of liver fibrosis. Curcumin is known to have an anti-fibrosis effect, but the specific mechanism needs to be elucidated. There is currently no evidence illustrating a connection between curcumin and the CXCL12/CXCR4 axis in liver fibrosis. Here, we investigated the contribution of curcumin on CXCL12/ CXCR4 biological axis in liver fibrosis. Our results showed that curcumin remarkably improved hepatic function and liver fibrosis, and the effects are similar as silymarin. The alleviation of liver fibrosis with curcumin treatment was associated with a reduction of CXCL12, CXCR4, α-SMA and RhoA. In addition, curcumin markedly inhibited the proliferation and migration of HSC-T6 cells. This study indicates that curcumin could protect against hepatic stellate cells activation and migration by inhibiting the CXCL12/CXCR4 biological axis in liver fibrosis.

Topics: Animals; Cell Line; Cell Movement; Cell Proliferation; Chemokine CXCL12; Curcumin; Hepatic Stellate Cells; Liver Cirrhosis; Male; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, CXCR4

Aberrant succinate accumulation emerges as a unifying mechanism for inflammation and oxidative stress. This study aims to investigate whether curcumin ameliorates hepatic fibrosis via blocking succinate signaling.. We investigated the effects of curcumin on hepatic succinate accumulation and liver fibrosis in mice fed a high-fat diet (HFD). Meanwhile, we stimulated mouse primary hepatic stellate cells (HSCs) with succinate and observed the inhibitory effects of curcumin on succinate signaling.. Oral administration of curcumin and metformin combated mitochondrial fatty acid oxidation and reduced hepatic succinate accumulation due to the inhibition of succinate dehydrogenase (SDH) activity and demonstrated inhibitory effect on hepatic fibrosis. In mouse primary HSCs, curcumin prevented succinate- and CoCl. Hepatic succinate accumulation served as a metabolic signal to promote liver fibrosis through HIF-1α induction. Curcumin reduced succinate accumulation by combating fatty acid oxidation and prevented HSCs activation by blocking succinate/HIF-1α signaling pathway.

Topics: Animals; Curcumin; Diet, High-Fat; Hepatic Stellate Cells; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Liver Cirrhosis; Male; Mice, Inbred ICR; Models, Biological; Succinic Acid

Recent studies have strongly indicated the hepatoprotective effect of curcumin; however, the precise mechanisms are not well understood. This study aimed to determine the protective effect of curcumin on hepatic damage and hepatic insulin resistance in biliary duct ligated (BDL) fibrotic rat model. To accomplish this, male Wistar rats were divided into four groups (eight for each): sham group, BDL group, sham+Cur group and BDL+Cur group. The last two groups received curcumin at a dose of 100 mg/kg daily for 4 weeks. The mRNA/protein expression levels of Ras-related C3 botulinum toxin substrate 1 (Rac1), Rac1-GTP, dinucleotide phosphate oxidase 1 (NOX1), signal transducer and activator of transcription 3 (STAT3), suppressor of cytokine signalling 3 (SOCS3), insulin receptor substrate 1 (IRS1), extracellular signal-regulated kinase 1 (ERK1), specific protein 1 (Sp1) and hypoxia-inducible factor-1α (HIF-1α) were measured by real-time PCR and Western blotting, respectively. Fasting blood glucose, insulin and Leptin levels were determined and homoeostasis model assessment-estimated insulin resistance, as an index of insulin resistance, was calculated. Curcumin significantly attenuated liver injury and fibrosis, including amelioration of liver histological changes, reduction of hepatic enzymes, as well as decreased expression of liver fibrogenesis-associated variables, including Rac1, Rac1-GTP, NOX1, ERK1, HIF-1α and Sp1. Curcumin also attenuated leptin level and insulin resistance, which had increased in BDL rats (P<0·05). Furthermore, compared with the BDL group, we observed an increase in IRS1 and a decrease in SOCS3 and STAT3 expression in the curcumin-treated BDL group (P<0·05), indicating return of these parameters towards normalcy. In conclusion, Curcumin showed hepatoprotective activity against BDL-induced liver injury and hepatic insulin resistance by influencing the expression of some genes/proteins involved in these processes, and the results suggest that it can be used as a therapeutic option.

Topics: Animals; Bile Ducts; Curcumin; Gene Expression Profiling; Homeostasis; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Insulin Receptor Substrate Proteins; Insulin Resistance; Ligation; Liver Cirrhosis; Male; Malondialdehyde; Mitogen-Activated Protein Kinase 3; NADPH Oxidase 1; rac1 GTP-Binding Protein; Rats; Rats, Wistar; STAT3 Transcription Factor

In oriental medicine, curcumin is used to treat inflammatory diseases, and its anti-inflammatory effect has been reported in recent research. In this feasibility study, the hepatoprotective effect of curcumin was investigated using a rat liver cirrhosis model, which was induced with dimethylnitrosamine (DMN). Together with biochemical analysis, we used a magnetic resonance-based electrical conductivity imaging method to evaluate tissue conditions associated with a protective effect. The effects of curcumin treatment and lactulose treatment on liver cirrhosis were compared. Electrical conductivity images indicated that liver tissues damaged by DMN showed decreased conductivity compared with normal liver tissues. In contrast, cirrhotic liver tissues treated with curcumin or lactulose showed increased conductivity than tissues in the DMN-only group. Specifically, conductivity of cirrhotic liver after curcumin treatment was similar to that of normal liver tissues. Histological staining and immunohistochemical examination showed significant levels of attenuated fibrosis and decreased inflammatory response after both curcumin and lactulose treatments compared with damaged liver tissues by DMN. The conductivity imaging and biochemical examination results indicate that curcumin's anti-inflammatory effect can prevent the progression of irreversible liver dysfunction.

Topics: Animals; Anti-Inflammatory Agents; Curcumin; Dimethylnitrosamine; Electric Conductivity; Lactulose; Liver; Liver Cirrhosis; Rats; Rats, Sprague-Dawley

Although liver fibrosis is a major public health issue, there is still no effective drug therapy in the clinic. Fibroblast growth factor-inducible 14 (Fn14), a membrane receptor highly specifically expressed in activated hepatic stellate cells (HSCs), is the key driver of liver fibrosis, and thus, it has a great potential as a novel target for the development of effective treatment. Here, we identified a d-enantiomeric peptide ligand of Fn14 through mirror-image mRNA display. This included the chemical synthesis of a d-enantiomer of the target protein (extracellular domain of Fn14), identification of an l-peptide ligand of d-Fn14 using a constructed mRNA peptide library, and identification of a d-enantiomer of the l-peptide, which is a ligand of the natural Fn14 for reasons of symmetry. The obtained d-peptide ligand showed strong binding to Fn14 while maintaining high proteolytic resistance. As a targeting moiety, this d-peptide successfully mediated high selectivity of activated HSCs for liposomal vehicles compared to that of other major cell types in the liver and significantly enhanced the accumulation of liposomes in the liver fibrosis region of a carbon tetrachloride-induced mouse model. Moreover, in combination with curcumin as an encapsulated load, a liposomal formulation conjugated with this d-peptide showed powerful inhibition of the proliferation of activated HSCs and reduced the liver fibrosis to a significant extent in vivo. This Fn14-targeting strategy may represent a promising approach to targeted drug delivery for liver fibrosis treatment. Meanwhile, the mirror-image mRNA display can provide a new arsenal for the development of d-peptide-based therapeutics against a variety of human diseases.

Topics: Animals; Carbon Tetrachloride; Cell Line; Curcumin; Endocytosis; Hepatic Stellate Cells; Humans; Liposomes; Liver; Liver Cirrhosis; Male; Mice; Peptides; RNA, Messenger; TWEAK Receptor

Activation and proliferation of hepatic stellate cells (HSC) play an important role in the progress of liver fibrosis. HSC activation occurs in response to inflammatory cytokines, cellular interactions with immune cells, and morphogenetic signals. The literature hints to a role of the adaptor protein MyD88 in fibrosis. Although curcumin has been shown to exert inhibitory effects on the proliferation of HSC

Topics: Animals; Apoptosis; Cell Line; Cell Proliferation; Curcuma; Curcumin; Cytokines; Hepatic Stellate Cells; Liver Cirrhosis; Myeloid Differentiation Factor 88; Rats; RNA, Small Interfering

In liver cirrhosis with portal hypertension, the uneven distribution of vasoactive substances leads to increased intrahepatic vascular resistance and splanchnic vasodilatation. Angiogenesis also induces increased portal inflow and portosystemic collaterals. The collaterals may induce lethal complications such as gastroesophageal variceal hemorrhage, but the therapeutic effect of vasoconstrictors is still suboptimal due to poor collateral vasoresponsivenss. Curcumin has aroused much attention for its antifibrosis, vasoactive, and anti-angiogenesis actions. However, whether it affects the aforementioned aspects is unknown. Liver cirrhosis was induced by common bile duct ligation (CBDL) in Sprague-Dawley rats. Sham-operated rats were controls. CBDL and sham rats were randomly allocated to receive curcumin (600 mg/kg per day) or vehicle since the 15th day after BDL. On the 29th day, portal hypertension related parameters were surveyed. Portosystemic collateral

Topics: Animals; Curcumin; Cyclooxygenase 2; Disease Models, Animal; Gene Expression Regulation; Humans; Hypertension, Portal; Liver; Liver Cirrhosis; Mesenteric Artery, Superior; Neovascularization, Pathologic; Nitric Oxide Synthase Type III; Rats; Splanchnic Circulation; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factor Receptor-2; Vascular Resistance; Vasoconstriction

Hepatic fibrosis, a common scarring response to various forms of chronic liver injury, is a precursor to cirrhosis and liver cancer. During liver fibrosis, hepatic stellate cells (HSCs) initially activate and proliferate, which are responsible for the secretion of extracellular matrix components. However, these cells eventually senesce and are cleared by natural killer (NK) cells. Our previous researches have shown that the natural product curcumin could promote the senescence of activated HSC. In this study, we investigated how NK cells target senescent HSC and assessed the effect of this process on liver fibrosis. We found that senescent HSC induced by curcumin are susceptible to NK cells killing, due to the increased expression of NK cell activating ligand major histocompatibility complex class I chain-related genes A (MICA) and UL16-binding proteins 2 (ULBP2), but not Poliovirus Receptor (PVR). Further studies displayed that the interaction between NK cells and senescent LX2 cells stimulated granule exocytosis. Moreover, the inhibition of granule exocytosis weakened the cytotoxicity of NK cells and promoted the accumulation of senescent LX2 cells. Therefore, these aggregated data indicated that NK cells mediated clearance of senescent LX2 cells and granule exocytosis could play a protective role in the improvement of liver fibrosis.

Topics: Animals; Cell Death; Cell Line; Cellular Senescence; Curcumin; Exocytosis; Hepatic Stellate Cells; Humans; Killer Cells, Natural; Liver; Liver Cirrhosis; Male; Mice, Inbred ICR

To compare the effects of Curcumae Rhizoma/vinegar-processed Curcumae Rhizomaon immune hepatic fibrosis, proliferation of HSC-T6, and expressions of α-SMA and Procollagen I. The immunological liver fibrosis model was prepared through intraperitoneal injection with porcine serum 0.5 mL in each rat, twice a week, for 14 weeks. Expressions of serum ALT, AST, PC-Ⅲ, IV-C, LN, HA and HYP, MDA in liver tissues were observed after administration of Curcumae Rhizoma/vinegar-processed Curcumae Rhizoma (0.95, 1.90 g•kg⁻¹). The pathological changes in liver tissues were observed by HE staining. Masson staining and Sirius red staining were used to observe the expression of collagen in rat liver. HSC-T6 was cultured, and the proliferation of HSC-T6 was determined by MTT assay at different concentrations in 12, 24, 36, 48 h. The expressions of α-SMA and Procollagen I were detected by Real-time PCR. The results showed that expressions of serum ALT, AST, PC-Ⅲ, IV-C, LN and HA in Curcumae Rhizoma/vinegar-processed Curcumae Rhizoma groups (0.95, 1.90 g•kg⁻¹) were significantly lower than model group; in terms of effect, vinegar-processed Curcumae Rhizoma group was superior to Curcumae Rhizoma group. Curcumae Rhizoma/vinegar-processed Curcumae Rhizoma containing serum could inhibit the proliferation of HSC-T6 in a dose-effect and time-effect manner. Expressions of α-SMA and Procollagen I in HSC-T6 were decreased after 24 h, especially in 20% vinegar-processed Curcumae Rhizoma containing serum group (P<0.01). Both Curcumae Rhizoma/vinegar-processed Curcumae Rhizoma could reduce immune hepatic fibrosis to varying extent. Their anti-hepatic fibrosis mechanism may be correlated with inhibition of the proliferation of HSC-T6, and reduction of the formation of extracellular matrix and promotion of its degradation.

Topics: Acetic Acid; Actins; Animals; Cell Line; Cell Proliferation; Curcuma; Drugs, Chinese Herbal; Hepatic Stellate Cells; Liver Cirrhosis; Procollagen; Rats; Rhizome

Liver fibrosis is a major health problem that has no satisfactory medication. Curcumin, (CUR) although known for its antifibrotic activity, has limited medicinal use owing to its poor oral pharmacokinetic properties and targeting efficiency. The current study aimed at exploring the ability of zein (ZN) nanospheres to improve the liver targeting and antifibrotic activity of CUR in a mouse model of carbon tetrachloride (CCl4)-induced liver fibrosis. Four different formulae of ZN-loaded CUR were prepared and examined in terms of particle size, zeta potential, encapsulation efficiency, and in vitro permeation. The formula containing a CUR to ZN ratio of 1:3 showed optimum nanosphere properties and was subjected to further investigations. Under a scanning electron microscope, the selected formula showed spherical particles with uniform size distribution. In normal mice, the selected formula exhibited improved bioavailability and liver targeting efficiency compared to raw CUR. The nanosphere preparation also offered significant protection against CCl4-induced liver function deterioration, histopathological changes, and oxidative stress in mice. Compared to raw CUR, CUR-ZN was significantly more effective in attenuating the rise in hepatic gene expression of collagen-1, tissue inhibitor of metalloproteinase-2, and transforming growth factor beta, as well as the downregulation of matrix metalloproteinase-2 expression. Masson's trichrome staining confirmed the higher antifibrotic activity of the nanospheres that ameliorated the rise in hepatic hydroxyproline content and collagen-1-immunopositive areas in mice liver sections. In conclusion, CUR-ZN nanospheres demonstrated improved liver targeting efficiency and antifibrotic activity in comparison to raw CUR in CCl4-induced liver fibrosis in mice.

Topics: Animals; Antioxidants; Carbon Tetrachloride; Curcumin; Drug Delivery Systems; Liver; Liver Cirrhosis; Male; Mice; Nanospheres; Oxidative Stress; Zein

Activation of hepatic stellate cells (HSCs) is a pivotal event in liver fibrosis, which is characterized by dramatic disappearance of lipid droplets. However, the underlying molecular mechanisms are largely unknown. We aimed to explore the role of Wnt/β-catenin pathway in HSC lipogenesis and to examine the effects of curcumin in this molecular context.. Primary rat HSCs were cultured in vitro for experiments. The Wnt activator WAY-262611 and β-catenin activator lithium chloride (LiCl) were used to activate the pathway at distinct levels in HSCs. Cell proliferation, fibrogenic markers, intracellular lipids and triglyceride, and adipogenic transcription factors were examined in HSCs.. Both WAY-262611 and LiCl promoted proliferation and upregulated the expression of α-smooth muscle actin and α1(I) procollagen, but they decreased the contents of intracellular lipids and triglyceride in HSCs. Analyses of adipogenic transcription pattern showed that the two compounds reduced the expression of peroxisome proliferator-activated receptor γ, CCAAT/enhancer binding protein α, retinoid X receptor-α, and retinoic acid receptor-β, four key transcription regulators of HSC adipogenic phenotype. Curcumin also reduced the expression of Frizzled and β-catenin, upregulated the expression of adipogenic transcription factors, and restored lipid content in HSCs. However, both WAY-262611 and LiCl abrogated curcumin restoration of lipogenesis and inhibition of fibrogenic marker expression in HSCs.. Wnt/β-catenin pathway was a profibrogenic signaling and inhibited lipogenesis by suppressing adipogenic transcription pattern in HSCs. Blockade of this pathway was associated with curcumin stimulation of HSC lipogenesis. We revealed a novel mechanism underlying curcumin restoration of lipid droplets during HSC activation.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; beta Catenin; Biomarkers; Blotting, Western; Curcumin; Hepatic Stellate Cells; Lipid Metabolism; Lipogenesis; Liver Cirrhosis; Rats; Transcription Factors; Wnt Signaling Pathway

Curcumin exerts hepatoprotective effects via poorly defined mechanisms. Recently, some studies suggested that this effect was mediated by antagonizing CB1 receptors in hepatic stellate cells. The current study aimed to investigate whether CB1 antagonist, hemopressin, could potentiate the hepatoprotective effect of curcumin, in comparison with silymarin in bile duct-ligated (BDL) rats. Curcumin and hemopressin each alone and in combination ameliorated biochemical and structural fibrotic injury, and downregulated cyclooxygenase-2 (COX-2) and both mRNA and protein levels of nuclear factor kappa B (NF-κB) in fibrotic liver. In contrast to the previous studies, curcumin alone did not affect the gene expression of cannabinoid receptors. However, the combination of hemopressin and curcumin reduced the expression of CB1 in fibrotic liver. Surprisingly, silymarin upregulated CB2 receptors and downregulated CB1 at mRNA level more than all the administered drugs. Both curcumin and hemopressin each alone decreased lipid peroxidation product, malondialdehyde (MDA), while the combination increased the reduced glutathione content. All the administered drugs increased the hepatic antiapoptotic marker, Bcl2. Our study suggests that hemopressin potentiates the hepatoprotective effect of curcumin on fibrotic liver. We identified a new mechanism of the hepatoprotective effect of silymarin via modulation of cannabinoid receptors in fibrotic liver.

Topics: Animals; Cholestasis; Curcumin; Cyclooxygenase 2; Drug Synergism; Glutathione; Hemoglobins; Lipid Peroxidation; Liver; Liver Cirrhosis; Male; NF-kappa B; Peptide Fragments; Proto-Oncogene Proteins c-bcl-2; Rats, Wistar; Receptor, Cannabinoid, CB1; Receptor, Cannabinoid, CB2; RNA, Messenger; Silymarin

Liver fibrosis is one of the major causes of morbidity and mortality worldwide and lacks efficient therapy. Recent studies suggest the curcumin protects liver from fibrosis. However, curcumin itself is in low bioavailable concentration when administered orally, and the protective mechanism remains poorly understood. The current study aimed to investigate whether a more stable derivative of curcumin, C66, protects against CCl4-inudced liver fibrosis and examine the underlying mechanism involving cannabinoid receptor (CB receptor). At a dose lower than curcumin itself, C66 displayed a superior anti-fibrotic effect. C66 significantly reduced collagen deposition, pro-inflammatory cytokine expression, and liver enzyme activities. Mechanistic study revealed that C66 treatment decreased CCl4-induced cannabinoid receptor 1 (CB1 receptor) expression and increased cannabinoid receptor 2 (CB2 receptor) expression, along with an inhibition of JNK/NF-κB-mediated inflammatory signaling. In conclusion, this curcumin derivative attenuates liver fibrosis likely involving a CB/JNK/NF-κB-mediated pathway.

Topics: Animals; Carbon Tetrachloride; Curcumin; Cytoprotection; Gene Expression Regulation; Hepatic Stellate Cells; JNK Mitogen-Activated Protein Kinases; Liver; Liver Cirrhosis; Male; Mice; Mice, Inbred C57BL; NF-kappa B; Protein Transport; Receptors, Cannabinoid; Signal Transduction

Activation of quiescent hepatic stellate cells (HSCs) is the major event in hepatic fibrogenesis, along with enhancement of cell proliferation and overproduction of extracellular matrix. Although inhibition of cell proliferation and induction of apoptosis are potential strategies to block the activation of HSCs, a better understanding of the senescence of activated HSCs can provide a new therapeutic strategy for prevention and treatment of liver fibrosis. The antioxidant curcumin, a phytochemical from turmeric, has been shown to suppress HSC activation in vitro and in vivo. The current work was aimed to evaluate the effect of curcumin on senescence of activated HSCs and to elucidate the underlying mechanisms. In this study, curcumin promoted the expression of senescence marker Hmga1 in rat fibrotic liver. In addition, curcumin increased the number of senescence-associated β-galactosidase-positive HSCs in vitro. At the same time, curcumin induced HSC senescence by elevating the expression of senescence markers P16, P21 and Hmga1, concomitant with reduced abundance of HSC activation markers α-smooth muscle actin and α1(I)-procollagen in cultured HSCs. Moreover, curcumin affected the cell cycle and telomerase activity. We further demonstrated that P53 pharmacological inhibitor pifithrin-α (PFT-α) or transfection with P53 siRNA abrogated the curcumin-induced HSC senescence in vitro. Meanwhile, curcumin disruption of P53 leading to increased senescence of activated HSCs was further verified in vivo. Further studies indicated that curcumin promoted the expression of P53 through a PPARγ activation-dependent mechanism. Moreover, promoting PPARγ transactivating activity by a PPARγ agonist 15d-PGJ2 markedly enhanced curcumin induction of senescence of activated HSCs. However, the PPARγ antagonist PD68235 eliminated curcumin induction of HSC senescence. Taken together, our results provided a novel insight into the mechanisms underlying curcumin inhibition of HSC activation through inducing senescence.

Topics: Animals; Benzothiazoles; Cell Cycle Checkpoints; Cell Proliferation; Cellular Senescence; Curcumin; Cyclin-Dependent Kinase Inhibitor p16; Cyclin-Dependent Kinase Inhibitor p21; Enzyme Inhibitors; Hepatic Stellate Cells; HMGA1a Protein; Liver; Liver Cirrhosis; Male; Mice; Mice, Inbred ICR; PPAR gamma; Rats; Rats, Sprague-Dawley; RNA Interference; Signal Transduction; Toluene; Tumor Suppressor Protein p53

Recent research has demonstrated that advanced liver fibrosis in patients could be reversed, but no approved agents are available for the treatment and prevention of liver fibrosis in humans. Curcumin (CUR) is the principal curcuminoid of turmeric. Inhibitory effects of CUR and its underlying mechanisms in liver fibrogenesis have been explored. In the present study, we hypothesized that epigenetic mechanisms contribute to the protective effects of CUR against liver fibrosis. We used CCl4-induced liver injury in BALB/c mice and the rat hepatic stellate cell line HSC-T6 as experimental models. Genomic DNA methylation was analyzed by MeDIP-chip and verified by real-time PCR on MeDIP-enriched DNA. The mRNA and protein expressions of DNMT1, α-SMA, and Col1α1 were determined by real-time PCR and Western blotting, respectively. The methylation statuses of FGFR3, FZD10, Gpx4, and Hoxd3 were further confirmed by quantitative methylation-specific PCR (qMSP). Our results showed that CUR treatment reversed liver injury in vivo and in vitro, possibly through down regulation of DNMT1, α-SMA, and Col1α1 and by demethylation of the key genes. In conclusion, aberrant methylation is closely associated with liver fibrosis and CUR treatment may reverse liver fibrosis by epigenetic mechanisms.

Topics: Animals; Cell Line; Curcumin; DNA Methylation; Hepatic Stellate Cells; Humans; Liver; Liver Cirrhosis; Male; Mice; Mice, Inbred BALB C; Protective Agents; Proteins; Rats

Activation of hepatic stellate cells (HSCs) is characterized by expression of extracellular matrix and loss of adipogenic phenotype during liver fibrogenesis. Emerging evidence suggests that HSCs adopt aerobic glycolysis during activation. The present work aimed at investigating whether the anti-fibrogenic effects of curcumin was associated with interfering with glycolysis in HSCs. Primary rat HSCs were cultured in vitro. We demonstrated that inhibition of glycolysis by 2-deoxyglucose or galloflavin reduced the expression of α-smooth muscle actin (α-SMA) and α1(I)procollagen at both mRNA and protein levels, and increased the intracellular lipid contents and upregulated the gene and protein expression of adipogenic transcription factors C/EBPα and PPAR-γ in HSCs. Curcumin at 20 μM produced similar effects. Moreover, curcumin decreased the expression of hexokinase (HK), phosphofructokinase-2 (PFK2), and glucose transporter 4 (glut4), three key glycolytic parameters, at both mRNA and protein levels. Curcumin also reduced lactate production concentration-dependently in HSCs. Furthermore, curcumin increased the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), but AMPK inhibitor BML-275 significantly abolished the curcumin downregulation of HK, PFK2, and glut4. In addition, curcumin inhibition of α-SMA and α1(I)procollagen was rescued by BML-275, and curcumin upregulation of C/EBPα and PPAR-γ was abrogated by BML-275. These results collectively indicated that curcumin inhibited glycolysis in an AMPK activation-dependent manner in HSCs. We revealed a novel mechanism for curcumin suppression of HSC activation implicated in antifibrotic therapy. © 2016 IUBMB Life, 68(7):589-596, 2016.

Topics: Actins; AMP-Activated Protein Kinases; Animals; Collagen Type I; Collagen Type I, alpha 1 Chain; Curcumin; Deoxyglucose; Extracellular Matrix; Gene Expression Regulation; Glucose Transporter Type 4; Glycolysis; Hepatic Stellate Cells; Hexokinase; Humans; Isocoumarins; Liver; Liver Cirrhosis; Phosphofructokinase-2; Rats; Rats, Sprague-Dawley

Liver fibrosis is concomitant with monocyte infiltration, which has been highlighted as novel therapeutic targets for chronic liver diseases. We aimed to investigate whether curcumin might protect the liver from carbon tetrachloride (CCl4)-induced fibrosis by attenuating the recruitment of Gr1hi monocytes through inhibition of monocyte chemoattractant protein-1 (MCP-1).. Mice were intraperitoneally injected with CCl4 to induce liver fibrosis. Curcumin was orally administrated to mice. Hepatic inflammation and fibrosis were evaluated by analysis of liver function and hepatic histopathology. Infiltration of the Gr1hi monocytes was assessed by flow cytometry and immunohistochemistry. Moreover, mRNA expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and transforming growth factor (TGF)-β1 were determined by real time PCR. Hepatic expression of MCP-1 was determined by real time PCR and immunohistochemistry.. Curcumin significantly attenuated inflammation and fibrosis, as revealed by histological and biochemical analysis. The intrahepatic infiltration of Gr1hi monocytes was attenuated by curcumin administration. T cells, NK cells, NKT cells, and dendritic cells were not affected by curcumin. Curcumin significantly reduced the expression of TNF-α and TGF-β1, which is in line with the decreased numbers of intrahepatic Gr1hi monocytes. Intrahepatic MCP-1 expression of CCl4-challenged mice was inhibited by curcumin.. The anti-inflammatory and antifibrotic effects of curcumin could be contributed to its prevention of Gr1hi monocyte infiltration into the injured livers through inhibition of MCP-1. These new findings extend our understanding on the mechanisms of the anti-inflammatory and antifibrotic effects of curcumin.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antigens, Ly; Carbon Tetrachloride; Chemokine CCL2; Curcumin; Disease Models, Animal; Flow Cytometry; Humans; Immunohistochemistry; Inflammation; Liver; Liver Cirrhosis; Male; Mice; Mice, Inbred C57BL; Monocytes; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cells, Cultured; Curcumin; Drug Delivery Systems; Humans; Hyaluronan Receptors; Hyaluronic Acid; Liver Cirrhosis; Male; Mice, Inbred BALB C; Nanoparticles; Polyesters; Protective Agents; Rats; Thioacetamide

Accumulating evidence indicates that Hedgehog (Hh) signaling becomes activated in chronic liver injury and plays a role in the pathogenesis of hepatic fibrosis. Hepatic stellate cells (HSCs) are Hh-responsive cells and activation of the Hh pathway promotes transdifferentiation of HSCs into myofibroblasts. Targeting Hh signaling may be a novel therapeutic strategy for treatment of liver fibrosis. We previously reported that curcumin has potent antifibrotic effects in vivo and in vitro, but the underlying mechanisms are not fully elucidated. This study shows that curcumin downregulated Patched and Smoothened, two key elements in Hh signaling, but restored Hhip expression in rat liver with carbon tetrachloride-induced fibrosis and in cultured HSCs. Curcumin also halted the nuclear translocation, DNA binding, and transcription activity of Gli1. Moreover, the Hh signaling inhibitor cyclopamine, like curcumin, arrested the cell cycle, induced mitochondrial apoptosis, reduced fibrotic gene expression, restored lipid accumulation, and inhibited invasion and migration in HSCs. However, curcumin's effects on cell fate and fibrogenic properties of HSCs were abolished by the Hh pathway agonist SAG. Furthermore, curcumin and cyclopamine decreased intracellular levels of adenosine triphosphate and lactate, and inhibited the expression and/or function of several key molecules controlling glycolysis. However, SAG abrogated the curcumin effects on these parameters of glycolysis. Animal data also showed that curcumin downregulated glycolysis-regulatory proteins in rat fibrotic liver. These aggregated data therefore indicate that curcumin modulated cell fate and metabolism by disrupting the Hh pathway in HSCs, providing novel molecular insights into curcumin reduction of HSC activation.

Topics: Animals; Antineoplastic Agents; Apoptosis; Curcuma; Curcumin; Glycolysis; Hedgehog Proteins; Hepatic Stellate Cells; Liver Cirrhosis; Male; Patched Receptors; Phytotherapy; Random Allocation; Rats, Sprague-Dawley; Receptors, Cell Surface; Receptors, G-Protein-Coupled; Smoothened Receptor

We aimed to determine the effects of curcumin on liver fibrosis and to clarify the role of nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS) in a model of microsurgical cholestasis in the early stage of extrahepatic biliary atresia. Twelve-week-old Wistar rats were divided into four groups (n = 8): sham-operated rats (received olive oil after laparotomy); a curcumin group (received curcumin, 200 mg kg(-1) per day, after laparotomy); a biliary duct ligated group (BDL, received olive oil after operation); and a biliary duct ligated/curcumin group (BDL curc, received curcumin, 200 mg kg(-1) per day, after operation). After 3 weeks of treatment, curcumin did not modify blood plasma markers as well as the expressions of iNOS and NF-κB (p65) in the livers of the sham group. Interestingly, there was a significant increase in the extent of both liver and kidney fibrosis. On the other hand, despite a decrease in the expression of iNOS and NF-κB (p65), treatment with curcumin did not affect fibrosis enlargement due to bile duct ligation in the liver. In the BDL group, treatment with curcumin decreased the level of blood plasma markers investigated. In conclusion, treatment with curcumin was able to improve the functional properties of hepatocytes and to inhibit the upregulations of both NF-κB and iNOS in the BDL group; however, no beneficial effect was observed on the liver fibrosis developed in this model of cholestasis. Thus, in the studied model of microsurgical cholestasis, other factors different from NF-κB and iNOS are responsible for fibrotic processes in the liver.

Topics: Animals; Bile Ducts; Cholestasis; Curcumin; Disease Models, Animal; Humans; Liver Cirrhosis; Male; NF-kappa B; Nitric Oxide Synthase Type II; Rats; Rats, Wistar

Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) has been reported to play a role in the suppression of activated hepatic stellate cells (HSCs). Moreover, it has been demonstrated that hypermethylation of the PTEN promoter is responsible for the loss of PTEN expression during HSC activation. Methylation is now established as a fundamental regulator of gene transcription. MicroRNAs (miRNAs), which can control gene expression by binding to their target genes for degradation and/or translational repression, were found to be involved in liver fibrosis. However, the mechanism responsible for miRNA-mediated epigenetic regulation in liver fibrosis still remained unclear. In the present study, curcumin treatment significantly resulted in the inhibition of cell proliferation and an increase in the apoptosis rate through the up-regulation of PTEN associated with a decreased DNA methylation level. Only DNA methyltransferase 3b (DNMT3b) was reduced in vivo and in vitro after curcumin treatment. Further studies were performed aiming to confirm that the knockdown of DNMT3b enhanced the loss of PTEN methylation by curcumin. In addition, miR-29b was involved in the hypomethylation of PTEN by curcumin. MiR-29b not only was increased by curcumin in activated HSCs, but also was confirmed to target DNMT3b by luciferase activity assays. Curcumin-mediated PTEN up-regulation, DNMT3b down-regulation and PTEN hypomethylation were all attenuated by miR-29b inhibitor. Collectively, it is demonstrated that curcumin can up-regulate miR-29b expression, resulting in DNMT3b down-regulation in HSCs and epigenetically-regulated PTEN involved in the suppression of activated HSCs. These results indicate that miRNA-mediated epigenetic regulation may be a novel mechanism suppressing liver fibrosis.

Topics: Animals; Antineoplastic Agents; Apoptosis; Blotting, Western; Carbon Tetrachloride; Cell Proliferation; Cells, Cultured; Chromosome Deletion; Chromosomes, Human, Pair 10; Curcumin; DNA (Cytosine-5-)-Methyltransferases; DNA Methylation; DNA Methyltransferase 3B; Gene Expression Regulation; Hepatic Stellate Cells; Humans; Liver Cirrhosis; Luciferases; Male; MicroRNAs; Promoter Regions, Genetic; Proto-Oncogene Proteins c-akt; PTEN Phosphohydrolase; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; RNA, Small Interfering

Hepatic stellate cell activation is a key cellular event in the development of liver fibrosis. Recently, Delta-like homolog 1 (DLK1) protein level has been shown to increase in HSC activation and serve as a new contributor to HSC activation and liver fibrosis. Curcumin, a natural yellow polyphenol, possesses therapeutic roles in many diseases including liver fibrosis and has long been used in traditional medicine. The present study was aimed to elucidate the effect of curcumin on DLK1 expression in HSCs in vitro and in vivo, which is still unknown. Our results demonstrated that curcumin reduced DLK1 expression in culture-activated HSCs and in rat model of liver fibrosis. The inhibitory effect of curcumin on DLK1 expression may be mediated in part by interruption of Shh signaling pathway, which contributes to the promotion effect of curcumin on the expression of PPAR-gamma, a key factor in inhibiting HSC activation. Our results in this study may reveal a new mechanisms through which curcumin exerts its inhibitory effect on HSC activation and liver fibrosis.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Blotting, Western; Cells, Cultured; Curcumin; Disease Models, Animal; Gene Expression; Hepatic Stellate Cells; Intercellular Signaling Peptides and Proteins; Liver Cirrhosis; Membrane Proteins; Rats; Rats, Sprague-Dawley; Thioacetamide

Non-alcoholic steatohepatitis (NASH) is a major risk factor for hepatic fibrogenesis. NASH is often found in diabetic patients with hyperglycemia. Hyperglycemia induces non-enzymatic glycation of proteins, yielding advanced glycation end-products (AGEs). Effects of AGEs are mainly mediated by two categories of cytoplasmic membrane receptors. Receptor for AGEs (RAGE) is associated with increased oxidative stress and inflammation, whereas AGE receptor-1 (AGE-R1) is involved in detoxification and clearance of AGEs. Activation of hepatic stellate cells (HSC) is crucial to the development of hepatic fibrosis. We recently reported that AGEs stimulated HSC activation likely by inhibiting gene expression of AGE-R1 and inducing gene expression of RAGE in HSC, which were eliminated by the antioxidant curcumin. This study is to test our hypothesis that curcumin eliminates the effects of AGEs on the divergent regulation of the two receptors of AGEs in HSC by interrupting the AGE-caused activation of leptin signaling, leading to the inhibition of HSC activation. We observed herein that AGEs activated leptin signaling by inducing gene expression of leptin and its receptor in HSC. Like AGEs, leptin differentially regulated gene expression of RAGE and AGE-R1. Curcumin eliminated the effects of AGEs in HSC by interrupting leptin signaling and activating transcription factor NF-E2 p45-related factor 2 (Nrf2), leading to the elevation of cellular glutathione and the attenuation of oxidative stress. In conclusions, curcumin eliminated the effects of AGEs on the divergent regulation of gene expression of RAGE and AGE-R1 in HSC by interrupting the AGE-caused activation of leptin signaling, leading to the inhibition of HSC activation.

Topics: Animals; Antineoplastic Agents; Cells, Cultured; Chromones; Curcuma; Curcumin; Gene Expression Regulation; Glycation End Products, Advanced; Hepatic Stellate Cells; Leptin; Liver Cirrhosis; Male; Mice; Mice, Inbred C57BL; Morpholines; Plant Extracts; Rats; Rats, Sprague-Dawley; Receptor for Advanced Glycation End Products; Receptors, Immunologic; Receptors, Leptin; Tyrphostins

Liver cirrhosis is the final consequence of a progressive fibrotic process characterized by excessive collagen deposition and destruction of the normal liver architecture. This study aimed to investigate the protective effects of curcumin, silybin-phytosome and alpha-R-lipoic acid against thioacetamide-induced cirrhosis. Male rats were allocated into five groups of which one group received saline and served as normal control. Animals from groups 2-5 were treated with thioacetamide administered intraperitoneally at a dose of 200 mg/kg 3 times per week for 7 weeks. Group 2 was left untreated while groups from 3 to 5 were given a daily oral dose of curcumin, silybin-phytosome or alpha-R-lipoic acid simultaneously with thioacetamide. Increases in hepatic levels of malondialdehyde (MDA) and protein carbonyls (Pr Co) associated with thioacetamide administration were partially blocked in those groups receiving supplements. Glutathione (GSH) depletion, collagen deposition, matrix metalloproteinase-2 (MMP-2) activity, transforming growth factor-β1 (TGF-β1) level as well as α-smooth muscle actin (α-SMA) and heat shock protein-47 (HSP-47) gene expressions were also decreased in response to supplements administration. Serological analysis of liver function and histopathological examination reinforced the results. In conclusion, the present study highlights the antioxidant and the antifibrotic potentials of these supplements against chronic liver diseases caused by ongoing hepatic damage.

Topics: Animals; Antioxidants; Biomarkers; Chemical and Drug Induced Liver Injury; Curcumin; Gene Expression Regulation; HSP47 Heat-Shock Proteins; Liver Cirrhosis; Male; Matrix Metalloproteinase 2; Oxidative Stress; Rats; Rats, Wistar; Silybin; Silymarin; Thioacetamide; Thioctic Acid; Transforming Growth Factor beta1

Hepatic fibrosis is concomitant with sinusoidal pathological angiogenesis, which has been highlighted as novel therapeutic targets for the treatment of chronic liver disease. Our prior studies have demonstrated that curcumin has potent antifibrotic activity, but the mechanisms remain to be elucidated. The current work demonstrated that curcumin ameliorated fibrotic injury and sinusoidal angiogenesis in rat liver with fibrosis caused by carbon tetrachloride. Curcumin reduced the expression of a number of angiogenic markers in fibrotic liver. Experiments in vitro showed that the viability and vascularization of rat liver sinusoidal endothelial cells and rat aortic ring angiogenesis were not impaired by curcumin. These results indicated that hepatic stellate cells (HSCs) that are characterized as liver-specific pericytes could be potential target cells for curcumin. Further investigations showed that curcumin inhibited VEGF expression in HSCs associated with disrupting platelet-derived growth factor-β receptor (PDGF-βR)/ERK and mTOR pathways. HSC motility and vascularization were also suppressed by curcumin associated with blocking PDGF-βR/focal adhesion kinase/RhoA cascade. Gain- or loss-of-function analyses revealed that activation of peroxisome proliferator-activated receptor-γ (PPAR-γ) was required for curcumin to inhibit angiogenic properties of HSCs. We concluded that curcumin attenuated sinusoidal angiogenesis in liver fibrosis possibly by targeting HSCs via a PPAR-γ activation-dependent mechanism. PPAR-γ could be a target molecule for reducing pathological angiogenesis during liver fibrosis.

Topics: Animals; Antineoplastic Agents; Apoptosis; Blotting, Western; Carbon Tetrachloride; Cell Proliferation; Cells, Cultured; Curcumin; Enzyme-Linked Immunosorbent Assay; Fluorescent Antibody Technique; Hepatic Stellate Cells; Liver Cirrhosis; Male; Neovascularization, Pathologic; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; Xenograft Model Antitumor Assays

Emerging evidence indicates that Wnt/β-catenin pathway is linked to the fibrosis of different organs including liver fibrosis. β-Catenin promotes hepatic stellate cells (HSCs) activation, a key event in the development of liver fibrosis, and has emerged as a novel mediator of fibrosis. Curcumin, a natural active ingredient derived from turmeric, possesses an inhibitory effect on liver fibrosis. This study is aimed to examine whether curcumin affects β-catenin expression/activity in HSCs and explores the underlying mechanisms.. The researchers used Western blot, real-time PCR, transfection assay and electrophoretic mobility shift assay and employed cultured HSCs and rat model of liver injury.. Results showed that curcumin could reduce β-catenin protein level in HSCs in vitro and in vivo. Both β-catenin transactivation activity and DNA-binding activity were suppressed by curcumin. Moreover, nuclear β-catenin protein level was decreased by curcumin treatment. Further experiments suggested that delta-like homologue 1 contributed to curcumin inhibition of β-catenin transactivation activity in cultured HSCs.. Curcumin affects β-catenin pathway in HSCs and might suggest a possible new explanation for the effects of curcumin on HSC activation and liver fibrosis.

Topics: Animals; beta Catenin; Curcuma; Curcumin; Hepatic Stellate Cells; Intercellular Signaling Peptides and Proteins; Liver Cirrhosis; Membrane Proteins; Phytotherapy; Plant Extracts; Rats, Sprague-Dawley

The hepatoprotective effects of curcumin against alcohol-induced hepatic fibrosis have rarely been discussed and its mechanisms of action in alcohol-induced liver disease remain unknown. In this study, serum alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured to assess hepatic function; histopathological and immunohistochemical observations were used to evaluate pathological and specific molecular changes in liver tissue and flow cytometry was used to detect the apoptosis in cultured hepatic stellate cells (HSCs), the major fibrogenic cells in the liver; PCR and western blot analysis were employed to evaluate the changes in the expression of molecules and signaling pathways. We demonstrate that curcumin alleviates alcohol-induced hepatic fibrosis by affecting the HSCs. We found that the administration of curcumin inhibited alcohol-induced HSC proliferation and even induced HSC apoptosis by stimulating endoplasmic reticulum (ER) stress. We also found that by suppressing the transforming growth factor-β (TGF-β)/Smad signaling pathway, the administration of curcumin impaired the production of extracellular matrix proteins in alcohol-stimulated HSCs. These results indicate that curcumin exerts its hepatoprotective effects against alcohol-induced hepatic fibrosis by inhibiting the proliferation and inducing the apoptosis of HSCs by stimulating ER stress and deactivating HSCs by suppressing the TGF-β/Smad signaling pathway.

Topics: Animals; Cell Proliferation; Collagen Type I; Curcumin; Endoplasmic Reticulum Stress; Ethanol; Fibronectins; Hepatic Stellate Cells; Liver; Liver Cirrhosis; Male; Protective Agents; Rats, Sprague-Dawley; Signal Transduction; Smad Proteins; Transforming Growth Factor beta

High fat diet (HFD) is associated with oxidative stress induced fatty liver. Curcumin, an extract of Curcuma longa, has been shown to possess potent antioxidant and hypolipidemic properties. In this study, we investigated the effect of curcumin treatment on hepatic heme oxygenase-1 (HO-1) expression along with pro-oxidant-antioxidant status and lipid accumulation in rats fed an HFD. Male Sprague-Dawley rats were distributed among 4 groups: Group 1, which was fed the control diet (10% of total calories from fat); Group 2, which was fed the HFD (60% of total calories from fat); and groups 3 and 4, which received the HFD supplemented with curcumin and the control diet supplemented with curcumin (1 g/kg diet; w/w), respectively, for 16 weeks. HFD caused increases in hepatic lipid levels, production of reactive oxygen species, and lipid peroxidation. Further, HO-1 expression was significantly decreased. Histopathological examination showed hepatic fat accumulation and slight fibrotic changes. Curcumin treatment reduced hepatic lipids and oxidative stress parameters, and HO-1 expression was significantly increased. These findings suggest that increased HO-1 expression, along with suppressed oxidative stress as well as reduced hepatic fat accumulation and fibrotic changes, contribute to the beneficial effects of curcumin in attenuating the pathogenesis of fatty liver induced metabolic diseases.

Topics: Animals; Antioxidants; Curcuma; Curcumin; Diet, High-Fat; Fatty Liver; Gene Expression; Heme Oxygenase-1; Lipid Metabolism; Lipid Peroxidation; Liver; Liver Cirrhosis; Male; Rats, Sprague-Dawley; Reactive Oxygen Species

The ERK/HIF-1α signaling pathway is believed to play an important role in the genesis of progressive fibrosis. An increasing expression of HIF-1α and ERK accompanies CCl4-induced liver fibrosis in rats. Curcumin is verified to have antifibrotic effects in several kinds of liver fibrosis models. There is no specific evidence illustrating a connection between curcumin and the HIF-1α/ERK pathway in rat liver fibrosis induced by CCl4. In this study, liver fibrosis was induced by CCl4 in treated rats. The data demonstrated that curcumin was able to attenuate liver fibrosis and inhibit the proliferation of HSC. Moreover, curcumin could remarkably elevate the hepatic function by decreasing serum levels of ALT, AST and ALP, and increasing levels of ALB, TP and α-SMA, Col III mRNA expression. Meanwhile, ECM status could also be reflected by curcumin treatment. The alleviation with curcumin treatment was associated with inhibition of HIF-1α and phosphor-ERK. This study indicates that curcumin alleviates fibrosis by reducing the expression of HIF-1α partly through the ERK pathway.

Topics: Animals; Carbon Tetrachloride; Cell Proliferation; Curcumin; Hypoxia-Inducible Factor 1, alpha Subunit; Liver; Liver Cirrhosis; Liver Function Tests; Male; MAP Kinase Signaling System; Protective Agents; Rats; Rats, Sprague-Dawley; Signal Transduction

The pharmacological activities of herbal extracts can be enhanced by complex formation. In this study, we manipulated cyanidin and delphinidin-rich extracts to form an anthocyanin complex (AC) with turmeric and evaluated activity against inflammation and periductal fibrosis in Opisthorchis viverrini-infected hamsters. The AC was prepared from anthocyanins extracted from cobs of purple waxy corn (70%), petals of blue butterfly pea (20%) and turmeric extract (10%), resulting in an enhanced free-radical scavenging capacity. Oral administration of AC (175 and 700 mg/kg body weight) every day for 1 month to O. viverrini-infected hamsters resulted in reduced inflammatory cells and periductal fibrosis. Fourier transform infrared spectroscopy and partial least square discriminant analysis suggested nucleic acid changes in the O. viverrini-infected liver samples, which were partially prevented by the AC treatment. AC reduced 8-oxodG formation, an oxidative DNA damage marker, significantly decreased levels of nitrite in the plasma and alanine aminotransferase activity and increased the ferric reducing ability of plasma. AC also decreased the expression of oxidant-related genes (NF-κB and iNOS) and increased the expression of antioxidant-related genes (CAT, SOD, and GPx). Thus, AC increases free-radical scavenging capacity, decreases inflammation, suppresses oxidative/nitrative stress, and reduces liver injury and periductal fibrosis in O. viverrini-infected hamsters.

Topics: Animals; Anthocyanins; Anti-Inflammatory Agents; Antioxidants; Cricetinae; Curcuma; DNA Damage; Gene Expression; Liver Cirrhosis; Male; Mesocricetus; Opisthorchiasis; Opisthorchis; Phenols; Pisum sativum; Plant Extracts; Zea mays

The aim of this study was to elucidate the effects of zedoary turmeric oil (ZTO) on P450 activities (CYP1A2, CYP2C9, CYP2C19, CYP2B6, CYP2D6 and CYP3A4) in rats with liver cirrhosis induced by thioacetamide (TAA). For the induction of liver cirrhosis, rats were given TAA in their drinking water at a concentration of 0.03% for consecutive 5 weeks and then 0.04% for the next consecutive 5 weeks throughout the establishment of cirrhosis. Then the cirrhotic rats were ip given saline, ZTO 100, 200 and 400 mg/kg, respectively, once daily for 2 weeks. When cirrhosis model was established at week 10, all rats of five groups were administered intragastrically with 15 mg/kg phenacetin, 0.6 mg/kg tolbutamide, 15 mg/kg omeprazole, 15 mg/kg bupropion, 15 mg/kg metoprolol, and 10 mg/kg midazolam. Blood samples were collected at a series of time-points and the concentrations of probe drugs in plasma were determined by HPLC-MS/MS. The degree of liver cirrhosis was assessed by HE staining. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) from the model group increased by approximately 4-fold, and a decreased level of albumin (Alb) was also observed, as compared to the control group (P < 0.05). However, ZTO was found to reverse those changes of serum levels observed in the model group, and the 200 mg/kg ZTO treatment group showed the most obvious reverse tendency with significantly decreased ALT, AST and increased Alb levels (P < 0.05). The results indicated that ZTO with the dose of 100 mg/kg could inhibit the activities of CYP450 isoforms CYP2C9 and CYP2D6 in vivo in cirrhotic rats induced by TAA, while ZTO with the dose of 400 mg/kg could induce the activity of CYP2C19 in vivo in cirrhotic rats induced by TAA. However, ZTO showed no influence on cirrhotic rat hepatic CYP1A2, CYP2B6 and CYP3A4 activity in vivo. This has certain guiding significance to clinical treatment.

Topics: Animals; Curcuma; Cytochrome P-450 Enzyme System; Disease Models, Animal; Liver; Liver Cirrhosis; Male; Plant Extracts; Rats; Rats, Sprague-Dawley; Thioacetamide

Neoangiogenesis and the development of an abnormal angio-architecture in the liver are strongly linked with progressive fibrogenesis. This study aimed to evaluate the ability of curcumin to protect liver fibrosis-associated angiogenesis and capillarization of the sinusoids in experimental rats. Liver fibrosis was induced by intraperitoneal injection of carbon tetrachloride (CCl₄) with or without curcumin for 6 weeks. The results suggest that curcumin treatment markedly attenuated CCl₄-induced liver fibrosis, as assessed by histology and hydroxyproline content, and inhibited hepatic stellate cell activation. Curcumin ameliorated hepatic angiogenesis, as assessed by measuring microvessel density using Von Willebrand factor staining and by examining the expression of the endothelial cell markers CD31 and vascular endothelial growth factor receptor (VEGFR)-2 in the livers. Pathologic remodeling of liver sinusoidal capillarization, as assessed by electron-microscopic analysis of Disse's space and by evaluation of the levels of basement membrane protein expression, was also attenuated by curcumin administration. The intrahepatic gene or protein expression of hypoxia-inducible factor-1α, VEGFR-1, placental growth factor, and cyclooxygenase-2 decreased with treatment with curcumin in fibrotic rats. In conclusion, curcumin ameliorates hepatic angiogenesis and sinusoidal capillarization in CCl₄-induced rat liver fibrosis through suppressing multiple proangiogenic factors.

Topics: Angiogenesis Inhibitors; Animals; Blotting, Western; Capillaries; Carbon Tetrachloride Poisoning; Curcumin; Hepatic Veno-Occlusive Disease; Hydroxyproline; Immunohistochemistry; Liver; Liver Cirrhosis; Male; Microscopy, Electron, Transmission; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction

Activation of hepatic stellate cells (HSCs) is a pivotal event leading to extracellular matrix (ECM) overproduction during hepatic fibrogenesis. Compelling evidence indicates that cannabinoid receptors (CBRs) play an important role in chronic liver disease. Antagonism of hepatic CBR type 1 (CBR1) could be a novel therapeutic strategy for liver fibrosis. Our previous studies have demonstrated that curcumin has potent antifibrotic activity, but the mechanisms remain to be elucidated. The current work was to examine the curcumin effect on CBRs system and its relevance to inhibition of ECM expression in HSCs. Our in vivo data demonstrated that curcumin ameliorated fibrotic injury, and downregulated CBR1 but upregulated CBR2 at both mRNA and protein levels in rat fibrotic liver caused by carbon tetrachloride. The subsequent in vitro investigations showed that curcumin reduced the mRNA and protein abundance of CBR1 in cultured HSCs and decreased the expression of three critical ECM proteins. Further analyses revealed that CBR1 agonist abrogated the curcumin inhibition of ECM expression, but CBR1 antagonist mimicked and reinforced the curcumin effects. Autodock simulations predicted that curcumin could bind to CBR1 with two hydrogen bonds. Collectively, our current studies revealed that curcumin reduction of liver fibrosis was associated with modulation of CBRs system and that antagonism of CBR1 contributed to curcumin inhibition of ECM expression in HSCs.

Topics: Animals; Carbon Tetrachloride; Curcumin; Extracellular Matrix; Extracellular Matrix Proteins; Gene Expression Regulation; Hepatic Stellate Cells; Liver Cirrhosis; Male; Models, Molecular; Protein Conformation; Rats; Rats, Sprague-Dawley; Receptor, Cannabinoid, CB1

Curcumin has been extensively studied for its therapeutic effects in a variety of disorders. Fermented soy consumption is associated with a low incidence rate of chronic diseases in many Asian countries. The aim of this study was to investigate the potential underlying mechanisms of the effect of a phyto-power dietary supplement on liver fibrosis. Sprague-Dawley rats were intraperitoneally injected with dimethylnitrosamine (DMN; 10 mg kg(-1)) three times a week for four consecutive weeks. A phyto-power dietary supplement (50 or 100 mg kg(-1)) was administered by oral gavage daily for four weeks. Liver morphology, function, and fibrotic status were examined in DMN induced hepatic fibrogenesis. However, a phyto-power dietary supplement alleviated liver damage as indicated by histopathological examination of the α-smooth muscle actin (α-SMA) and collagen I, accompanied by the concomitant reduction of transforming growth factor-β1 (TGF-β1) and matrix metalloproteinase 2 (MMP2). These data indicate that the phyto-power dietary supplement may inhibit the TGF-β1/Smad signaling and relieve liver damage in experimental fibrosis.

Topics: Actins; Administration, Oral; Animals; Collagen; Curcumin; Dietary Supplements; Dimethylnitrosamine; Liver; Liver Cirrhosis; Male; Matrix Metalloproteinase 2; Rats; Rats, Sprague-Dawley; Signal Transduction; Smad2 Protein; Smad3 Protein; Transforming Growth Factor beta1

Liver fibrosis is a major health problem that can lead to the development of liver cirrhosis and hepatocellular carcinoma. On the other hand, several antioxidants have been shown to possess protective effect against liver fibrosis. Therefore, in the present work, the effectiveness of curcumin, α-lipoic acid, and N-acetylcysteine in protecting against carbon tetrachloride (CCl(4))-induced liver fibrosis as well as the mechanism(s) implicated in this protective effect was studied. The antioxidants used in this study resulted in hepatoprotective effect as evident by substantial decreases in collagen deposition in histopathological examinations in addition to significant decrease in serum levels of alanine aminotransferase, aspartate aminotransferase, gamma glutamyl transpeptidase, bilirubin, and transforming growth factor-alpha (TGF-α) as well as hepatic malondialdehyde concentration, with a concurrent increase in serum matrix metalloproteinase-13 (MMP-13) and hepatic reduced glutathione (GSH) levels as compared to CCl(4) fibrotic group. In conclusion, curcumin, α-lipoic acid, and N-acetylcysteine protect rats against CCl(4)-induced liver fibrosis most possibly through their antioxidant activities and their capacities to induce MMP-13 and to inhibit TGF-α levels.

Topics: Acetylcysteine; Alanine Transaminase; Animals; Antioxidants; Aspartate Aminotransferases; Bilirubin; Carbon Tetrachloride; Curcumin; gamma-Glutamyltransferase; Glutathione; Liver Cirrhosis; Male; Malondialdehyde; Matrix Metalloproteinase 13; Rats; Rats, Wistar; Thioctic Acid; Transforming Growth Factor alpha

Inflammation and hepatic stellate cell (HSC) activation are the most crucial steps in the formation of hepatic fibrosis. Hepatocytes damaged by viral or bacterial infection, alcohol or toxic chemicals initiate an inflammatory response that activates collagen production by HSCs. Recent studies indicate curcumin has liver-protective effects due to its anti-inflammatory, antioxidant and anticancer activities; however, the mechanisms are not well understood. In this study, we show that curcumin protected against hepatic fibrosis in BALB/c mice in vivo by inhibiting HSC activation, inflammatory responses and inducing apoptosis of damaged hepatocytes. Using the thioacetamide (TAA)-induced hepatic fibrosis animal model, we found that curcumin treatment up-regulated P53 protein expression and Bax messenger RNA (mRNA) expression and down-regulated Bcl-2 mRNA expression. Together, these responses increased hepatocyte sensitivity to TAA-induced cytotoxicity and forced the damaged cells to undergo apoptosis. Enhancing the tendency of damaged hepatocytes to undergo apoptosis may be the protective mechanism whereby curcumin suppresses inflammatory responses and hepatic fibrogenesis. These results provide a novel insight into the cause of hepatic fibrosis and the cytoprotective effects curcumin has on hepatic fibrosis suppression.

Topics: Animals; Antineoplastic Agents; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Cell Line; Cell Proliferation; Curcumin; DNA Damage; Gene Expression Regulation; Hepatic Stellate Cells; Hepatocytes; In Situ Nick-End Labeling; Inflammation; Liver; Liver Cirrhosis; Male; Mice; Mice, Inbred BALB C; RNA, Messenger; Thioacetamide; Tumor Suppressor Protein p53

Increasingly, studies demonstrate the effectiveness of acupuncture therapy against liver fibrosis. Curcumin is a natural product with antifibrotic effects, but has poor pharmacokinetic profiles. This study aimed to evaluate whether acupuncture combined with curcumin could more potently attenuate liver fibrosis in chemical intoxicated rats.. 60 Sprague-Dawley male rats were randomly divided into control, model, sham, acupuncture, curcumin and combination therapy groups. During the establishment of fibrosis using carbon tetrachloride (CCl(4)), acupuncture at LR3, LR14, BL18 and ST36 and/or curcumin treatment by mouth were performed simultaneously. After treatment, pathological indexes and histology for hepatic injury and fibrogenesis were detected. The expression of extracellular matrix (ECM) components was also determined.. Acupuncture combined with curcumin potently protected the liver from CCl(4)-induced injury and fibrogenesis, as indicated by reduced levels of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, hyaluronic acid, laminin and procollagen III. Combined use also led to significant liver histological improvements. Furthermore, combined use effectively inhibited ECM expression such as α-smooth muscle actin, fibronectin and α1(1) collagen.. Acupuncture treatment could significantly enhance the antifibrotic efficacy of curcumin on CCl(4)-induced hepatic fibrosis in rats in vivo, suggesting that a combination of acupuncture with curcumin may be exploited for the prevention of hepatic fibrosis.

Topics: Acupuncture Therapy; Animals; Carbon Tetrachloride; Combined Modality Therapy; Curcumin; Extracellular Matrix; Humans; Liver Cirrhosis; Male; Random Allocation; Rats; Rats, Sprague-Dawley

The aim of the study was to investigate the effect of curcumin on the liver fibrosis induced by carbon tetrachloride (CCl(4)) in rats, and to elucidate its underlying molecular mechanisms. Rats were administered with CCl(4) together with or without curcumin for 6 weeks. Hepatic damage was evaluated by analysis of liver function tests in serum. Hepatic histopathology and collagen content were employed to quantify liver fibrosis; and activated hepatic stellate cells were assessed. Moreover, the mRNA and protein expression levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, high-mobility group box 1 (HMGB1), Toll like receptor (TLR) 2 and TLR4 were determined by quantitative real time PCR, Western blot or immunohistochemistry. Treatment with curcumin significantly attenuated CCl(4)-induce liver injury, hepatic inflammation and reduced the levels of proinflammatory mediators (TNF-α, IL-6 and MCP-1). Moreover, curcumin significantly inhibited extracellular matrix deposition, reduced the number of activated stellate cells, and decreased the levels of HMGB1, TLR4 and TLR2 expression in the rat model of fibrogenesis. These results suggest that curcumin could be an effective agent for preventing liver fibrosis and its mechanism may in part be a consequence of the reduction TLR2, TLR4 and HMGB1 expression.

Topics: Animals; Base Sequence; Carbon Tetrachloride; Curcumin; DNA Primers; HMGB1 Protein; Liver Cirrhosis; Male; Polymerase Chain Reaction; Rats; Rats, Sprague-Dawley; Toll-Like Receptor 2; Toll-Like Receptor 4

Acupuncture treatment has been increasingly used to treat chronic liver diseases. We previously reported that acupuncture combined with curcumin, a natural antifibrotic compound, could remarkably attenuate liver fibrosis in chemically intoxicated rats, but the underlying molecular mechanisms are poorly understood. The present study was aimed at investigating the effects of acupuncture combined with curcumin on platelet-derived growth factor (PDGF) signalling and extracellular matrix (ECM) regulation in the fibrotic liver.. A total of 60 Sprague-Dawley male rats were randomly divided into control, model, sham, acupuncture, curcumin and combination treatment groups. During the establishment of fibrosis using carbon tetrachloride (CCl(4)), acupuncture at LR3, LR14, BL18 and ST36 and/or curcumin treatment by mouth were performed simultaneously. After treatment, serum PDGF levels were measured. Protein and mRNA expression of key effectors in PDGF pathway and fibrinolysis in the liver was determined.. Acupuncture combined with curcumin potently reduced serum PDGF levels and selectively disrupted the PDGF-βR/extracellular signal-regulated kinase (ERK) cascade. Combination treatment also significantly repressed expression of connective tissue growth factor and upregulated expression of matrix metalloproteinase-9, promoting fibrinolysis in the fibrotic liver.. The beneficial effects of acupuncture and its combination with curcumin could be attributed to the disruption of PDGF-βR/ERK pathway and stimulated ECM degradation in the fibrotic liver. Acupuncture treatment significantly enhanced curcumin effects at the molecular level. These findings may provide molecular insights into the potential of acupuncture combined with curcumin for prevention of hepatic fibrosis.

Topics: Acupuncture Therapy; Animals; Carbon Tetrachloride; Combined Modality Therapy; Curcumin; Extracellular Matrix; Extracellular Signal-Regulated MAP Kinases; Humans; Liver Cirrhosis; Male; Rats; Rats, Sprague-Dawley; Receptor, Platelet-Derived Growth Factor beta; Signal Transduction

At present there is no effective and accepted therapy for hepatic fibrosis. Transforming growth factor (TGF)-β1 signaling pathway contributes greatly to hepatic fibrosis. Reducing TGF-β synthesis or inhibiting components of its complex signaling pathway represent important therapeutic targets. The aim of the study was to investigate the effect of curcumin on liver fibrosis and whether curcumin attenuates the TGF-β1 signaling pathway.. Sprague-Dawley rat was induced liver fibrosis by carbon tetrachloride (CCl4) for six weeks together with or without curcumin, and hepatic histopathology and collagen content were employed to quantify liver necro-inflammation and fibrosis. Moreover, the mRNA and protein expression levels of TGF-β1, Smad2, phosphorylated Smad2, Smad3, Smad7 and connective tissue growth factor (CTGF) were determined by quantitative real time-PCR, Western blot, or immunohistochemistry.. Rats treated with curcumin improved liver necro-inflammation, and reduced liver fibrosis in association with decreased α-smooth muscle actin expression, and decreased collagen deposition. Furthermore, curcumin significantly attenuated expressions of TGFβ1, Smad2, phosphorylated Smad2, Smad3, and CTGF and induced expression of the Smad7.. Curcumin significantly attenuated the severity of CCl4-induced liver inflammation and fibrosis through inhibition of TGF-β1/Smad signalling pathway and CTGF expression. These data suggest that curcumin might be an effective antifibrotic drug in the prevention of liver disease progression.

Topics: Animals; Carbon Tetrachloride; Curcuma; Curcumin; Disease Progression; Down-Regulation; Humans; Liver Cirrhosis; Male; Phosphorylation; Plant Extracts; Rats; Rats, Sprague-Dawley; Signal Transduction; Smad Proteins; Transforming Growth Factor beta1

Curcumin (CM), a biphenyl compound, possesses anti-inflammatory, antioxidant and antimicrobial activity. MicroRNAs (miRNAs) are small noncoding RNAs which regulate gene expression and the molecular mechanisms of several biological processes. Liver fibrosis is a major cause of hepatic dysfunction and cancer and there are few effective therapies emphasizing the need for new approaches to control. The present study was conducted to investigate the effect of curcumin (CM) on liver fibrosis through modulating the expression level of miRNAs (199 and 200), the main miRNAs associated with liver fibrosis. Induction of liver fibrosis by carbon tetrachloride (CCL4) was confirmed by histopathological examination. Mice were divided into 3 groups: group 1 were i.p injected with 10% CCL4 twice weekly for 4 weeks and then once a week for the next 4 weeks followed by 4 weeks with olive oil only. Group 2 were i.p injected with 10% CCL4 twice weekly for 4 weeks and then once a week for the next 4 weeks followed by curcumin (5 mg/mouse/day) once daily for the next 4 weeks. The third group was injected with olive oil. The expression level of miR-199 and miR-200 and some of their targeted genes were measured by real time PCR. miRNA (199 and 200) levels were significantly elevated in liver fibrotic tissues compared to control groups. Curcumin was significantly returned the expression levels of mir-199 and -200 with their associated target gene nearly to their normal levels. This is the first study that highlighted the effect of curcumin on liver fibrosis through regulation of miRNAs.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbon Tetrachloride; Curcumin; Disease Models, Animal; Gene Expression Regulation; Liver Cirrhosis; Mice; MicroRNAs; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Topics: Animals; Curcumin; Fatty Liver; Feeding Behavior; Fructose; Humans; Liver Cirrhosis; Non-alcoholic Fatty Liver Disease; Rats; Treatment Outcome

Hepatic stellate cells (HSC) play a pivotal role in liver fibrosis, and the clearance of activated HSC by apoptosis is associated with the resolution of liver fibrosis. The development of strategies that promote this process in a selective way is therefore important. We evaluated the effects of indole-3-carbinol (I3C), a nutritional component derived from vegetables from the Brassica family, on liver fibrosis and HSC apoptosis. The in vivo therapeutic effects of I3C were monitored in three rat models of liver fibrosis induced by porcine serum, bile duct ligation, or multiple hepatotoxic factors, and its proapoptotic effect and molecular mechanism were studied in vitro in HSC-T6, a rat HSC line. The results showed that I3C treatment significantly reduced the number of activated HSC in the livers of rats with liver fibrosis. In histopathology, I3C reduced hepatocyte degeneration and necrosis, accelerated collagen degradation, and promoted the reversal of liver fibrosis. I3C prescribed to HSC-T6 resulted in morphologic alterations typical of apoptosis and DNA cleavage to a nucleosomal ladder. Moreover, I3C significantly increased the HSC-T6 apoptosis rate and the expression ratio of Bax to Bcl-2. High-throughput protein array analysis indicated that the tumor necrosis factor-α/nuclear factor-κB (NF-κB) signal pathway participated in I3C-induced HSC-T6 apoptosis. Western blot and electrophoretic mobility-shift assay confirmed that I3C inhibited the phosphorylation of inhibitor of κB kinase α and inhibitor of κB-α and NF-κB DNA binding activity. In conclusion, I3C could promote the reverse process of liver fibrosis in vivo and induce apoptosis of activated HSC in vitro, which indicates the use of I3C as a potential therapeutic agent in liver fibrosis treatment.

Topics: Animals; Apoptosis; Bile Ducts; Carbon Tetrachloride; Curcumin; Electrophoretic Mobility Shift Assay; Enzyme Inhibitors; Hepatic Stellate Cells; I-kappa B Kinase; I-kappa B Proteins; Indoles; Liver; Liver Cirrhosis; Male; NF-kappa B; NF-KappaB Inhibitor alpha; Phosphorylation; Protein Array Analysis; Rats; Rats, Wistar; Signal Transduction; Solvents; Swine; Transfection

The present study was designed to examine the potential preventive and curative effects of curcumin, resveratrol, imatinib, rosiglitazone, losartan and bosentan (BOS) on Schistosoma mansoni-induced liver fibrosis in mice. Induction of liver fibrosis was produced in male Swiss mice by subcutaneous injection of S. mansoni cercariae per mouse. Mice were left for 28 days before starting the experiment then mice were divided into two main groups. The first group was further subdivided into experimental groups and started drug treatment at day 28 after infection and continued for 2 weeks in order to evaluate the potential preventive effects of the mentioned drugs on S. mansoni-induced liver fibrosis. The second group of mice were left for 2 weeks and then treated with praziquantel for two consecutive days to eradicate the worms and so stop egg disposition and further fibrosis development. Mice were then subdivided into the experimental groups and drug treatment was started for 2 weeks to evaluate their efficacy to decrease the developed fibrosis. At the end of the experiment period, mice were killed and serum was collected for the estimation of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin and albumin. Liver tissue was taken for the estimation of hepatic hydroxyproline content and histopathological examination to confirm the biochemical results. Results of the study indicate that curcumin and imatinib have potent antifibrotic activity both in suppressing and reversing S. mansoni-induced liver fibrosis, while resveratrol has beneficial effects only in suppressing the development of S. mansoni-induced liver fibrosis.

Topics: Alanine Transaminase; Animals; Aspartate Aminotransferases; Benzamides; Bilirubin; Curcumin; Hydroxyproline; Imatinib Mesylate; Liver; Liver Cirrhosis; Male; Mice; Piperazines; Pyrimidines; Resveratrol; Schistosoma mansoni; Schistosomiasis mansoni; Serum Albumin; Stilbenes

It has been demonstrated that β-elemene could protect against carbon tetrachloride (CCl(4))-induced liver fibrosis in our laboratory work, and the aim of this paper is to reveal the protective mechanisms of β-elemene. The hepatic fibrosis experimental model was induced by the hypodermical injection of CCl(4) in Wistar male rats. β-elemene was intraperitoneally administered into rats for 8 weeks (0.1 mL/100 g bodyweight per day), and plasma endotoxin content was assayed by biochemistry. The serum TNF-α level was detected using radioactive immunity. CD14 expression in rat livers was measured by immunohistochemistry and Western blot. The results showed that β-elemene can downregulate the levels of plasma endotoxins, serum TNF-α, and hepatic CD14 expression in rats with liver fibrosis. β-elemene plays an important role in downregulating the lipopolysaccharide signal transduction pathway, a significant pathway in hepatic fibrosis development.

Topics: Animals; Carbon Tetrachloride; Carbon Tetrachloride Poisoning; China; Curcuma; Disease Models, Animal; Down-Regulation; Endotoxins; Injections, Intraperitoneal; Lipopolysaccharide Receptors; Liver; Liver Cirrhosis; Male; Plant Preparations; Rats; Rats, Wistar; Sesquiterpenes; Tumor Necrosis Factor-alpha

Nonalcoholic steatohepatitis is characterized by the association of steatosis with hepatic cell injury, lobular inflammation and fibrosis. Curcumin is known for its antioxidant, anti-inflammatory and antifibrotic properties. The aim of this study was to test whether the administration of curcumin limits fibrogenic evolution in a murine model of nonalcoholic steatohepatitis. Male C57BL/6 mice were divided into four groups and fed a diet deficient in methionine and choline (MCD) or the same diet supplemented with methionine and choline for as long as 10 weeks. Curcumin (25 microg per mouse) or its vehicle (DMSO) was administered intraperitoneally every other day. Fibrosis was assessed by Sirius red staining and histomorphometry. Intrahepatic gene expression was measured by quantitative PCR. Hepatic oxidative stress was evaluated by staining for 8-OH deoxyguanosine. Myofibroblastic hepatic stellate cells (HSCs) were isolated from normal human liver tissue. The increase in serum ALT caused by the MCD diet was significantly reduced by curcumin after 4 weeks. Administration of the MCD diet was associated with histological steatosis and necro-inflammation, and this latter was significantly reduced in mice receiving curcumin. Curcumin also inhibited the generation of hepatic oxidative stress. Fibrosis was evident after 8 or 10 weeks of MCD diet and was also significantly reduced by curcumin. Curcumin decreased the intrahepatic gene expression of monocyte chemoattractant protein-1, CD11b, procollagen type I and tissue inhibitor of metalloprotease (TIMP)-1, together with protein levels of alpha-smooth muscle-actin, a marker of fibrogenic cells. In addition, curcumin reduced the generation of reactive oxygen species in cultured HSCs and inhibited the secretion of TIMP-1 both in basal conditions and after the induction of oxidative stress. In conclusion, curcumin administration effectively limits the development and progression of fibrosis in mice with experimental steatohepatitis, and reduces TIMP-1 secretion and oxidative stress in cultured stellate cells.

Topics: Actins; Alanine Transaminase; Animals; CD11b Antigen; Cells, Cultured; Chemokine CCL2; Choline; Choline Deficiency; Collagen Type I; Curcumin; Diet; Enzyme Inhibitors; Fatty Liver; Hepatic Stellate Cells; Humans; Liver; Liver Cirrhosis; Male; Methionine; Mice; Mice, Inbred C57BL; Muscle, Smooth; Oxidative Stress; Reactive Oxygen Species; Tissue Inhibitor of Metalloproteinase-1

Chronic infection with the liver fluke, Opisthorchis viverrini, induces advanced periductal fibrosis and is a relative risk factor for cholangiocarcinoma in Southeastern Asia. We examined the reducing effect of curcumin on hepatobiliary fibrosis using O. viverrini-infected hamsters supplemented with dietary 1% curcumin (w/w) as an animal model. The expression profile of matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs), cytokines, and collagens was assessed in relation to liver fibrosis. Histopathological studies revealed that curcumin had no effect on fibrosis at the short-term infection (21 days and 1 month); however, peribiliary fibrosis was significantly reduced after the long-term curcumin treatment for 3 months, compared to the untreated group. Expression of alpha-smooth muscle actin was associated with the reduction of liver fibrosis. A decrease in hepatic hydroxyproline level and mRNA expression of collagen I and III supported the reduction of fibrosis. The expression of TIMP-1, TIMP-2, and tumor necrosis factor-alpha genes was also decreased after curcumin treatment. In contrast, curcumin increased mRNA expression of MMP-13, MMP-7 (at 6 months), interleukin-1 beta, and transforming growth factor beta, implying that increased MMPs activity contributes to extracellular matrix degradation. These results suggest that curcumin reduces periductal fibrosis after long-term treatment by tissue resorption via inhibition of TIMPs expression and enhancement of MMPs expression mediated by cytokines. In conclusion, curcumin may serve as a promising nutraceutical agent exerting antifibrotic effect in O. viverrini-infected patients and contribute to cholangiocarcinoma prevention.

Topics: Actins; Animals; Collagen; Cricetinae; Curcumin; Drug Administration Schedule; Gene Expression Regulation; Hydroxyproline; Inflammation; Interleukin-1beta; Liver Cirrhosis; Liver Cirrhosis, Experimental; Male; Matrix Metalloproteinases; Opisthorchiasis; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2; Tissue Inhibitor of Metalloproteinases; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha

Liver fibrosis is one of the major health problems worldwide. Chronic alcohol abuse is one of the main causes of fibrosis. Ingestion of polyunsaturated fatty acids (PUFA) along with alcohol further aggravates the toxicity of alcohol. Fibrosis results due to increased deposition of extra cellular matrix (ECM). The degree of abnormal ECM degradation depends on the ratio of active matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The present work studied the influence of bis-desmethoxy curcumin analog (BDMC-A) on the expression of MMPs and TIMPs during alcohol and DeltaPUFA induced liver toxicity. Male albino Wistar rats were used for the study. The MMP expression was found to be increased in alcohol as well as DeltaPUFA treated rats and decreased in alcohol + DeltaPUFA treated rats. The levels of TIMPs and the collagen were increased in alcohol, DeltaPUFA, and alcohol + DeltaPUFA groups. Administration of BDMC-A significantly decreased the levels of collagen and TIMPs; and positively modulated the expression of MMPs. From this study, it is concluded that BDMC-A influences MMPs, TIMPs expression, and acts as an efficient anti-fibrotic agent.

Topics: Animals; Biomarkers; Collagen; Curcumin; Ethanol; Fatty Acids, Unsaturated; Liver; Liver Cirrhosis; Male; Matrix Metalloproteinases; Protective Agents; Rats; Rats, Wistar; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-2

Suppression of activation or fibrogenesis and induction of apoptosis, in hepatic stellate cells (HSCs) have been proposed as therapeutic strategies against liver fibrosis. Curcumin, an active compound isolated from yellow curry pigment of turmeric (Curcuma longa Linn), has been demonstrated to be an effective anti-inflammatory and antioxidant compound. In this study, we investigated the in vitro antifibrogenic effects of curcumin on HSCs at the concentration range of (1-40 microM). A cell line of rat HSCs (HSC-T6) was stimulated with transforming growth factor-beta1 (TGF-beta1). The inhibitory effects of curcumin (1.25 approximately 10 microM) on fibrosis-related markers including alpha-smooth muscle actin (alpha-SMA) and collagen were assessed. In addition, the induction effects of curcumin (20 approximately 40 microM) on apoptosis in HSC-T6 cells were also assessed by Hoechst and propidium iodide stains. Curcumin (1.25 approximately 10 microM) concentration-dependently suppressed TGF-beta1-induced alpha-SMA expression and collagen deposition in HSC-T6 cells, without cytotoxicity. Whereas, higher concentrations of curcumin (20 approximately 40 microM) induced cell apoptosis and cytochrome c release in HSC-T6 cells. Our results suggest that curcumin exerted antifibrotic effects, possibly through two different mechanisms depending on its concentrations. At lower concentrations (1.25 approximately 10 microM), curcumin exerted antifibrogenic effects, whereas at higher concentrations (20 approximately 40 microM), curcumin exerted induction of apoptosis in HSCs.

Topics: Actins; Animals; Apoptosis; Cell Line; Collagen; Curcumin; Cytochromes c; Hepatic Stellate Cells; Liver Cirrhosis; Rats; Transforming Growth Factor beta1

This study was designed to investigate the prophylactic effects and the mechanisms of curcumin on liver fibrosis in rats. Liver fibrosis was induced in 72 Sprague Dawley rats by intraperitoneal injection of carbon tetrachloride. Rats were divided into control, liver fibrosis, high, medium, and low dose curcumin (200, 100, and 50 mg kg(-1), respectively), and colchicine (0.1 mg kg(-1)) groups. After 8 weeks of treatment, histopathological examination was performed on hepatic tissues, and liver fibrosis was graded. Hepatic stellate cells activity was examined by smooth muscle alpha-actin immunohistochemistry staining, and apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling. The liver fibrosis score in the high, medium, and low dose curcumin group (5.79 +/- 1.80, 8.58 +/- 3.34, and 9.58 +/- 3.32, respectively) and the colchicine group (4.91 +/- 1.28) was significantly lower than in the fibrosis group (20.40 +/- 3.38, P < 0.01). The ratio of activated hepatic stellate cells in the three curcumin groups (0.97 +/- 0.69, 2.06 +/- 0.58, and 3.49 +/- 1.03, respectively) and the colchicine group (0.78 +/- 0.31) was significantly lower than in the fibrosis group (6.08 +/- 1.13, P < 0.05). The apoptosis index in the three curcumin groups (0.57 +/- 0.21, 0.37 +/- 0.22, and 0.34 +/- 0.21, respectively) was higher than in the fibrosis (0.09 +/- 0.09, P < 0.05) or the colchicine group (0.16 +/- 0.19, P < 0.05). Curcumin prevents carbon tetrachloride-induced liver fibrosis in rats. The prevention of liver fibrosis may be due to the inhibition of the activation of hepatic stellate cells and induction of their apoptosis.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; Carbon Tetrachloride; Curcumin; Hepatic Stellate Cells; In Situ Nick-End Labeling; Lipid Peroxidation; Liver Cirrhosis; Male; Rats; Rats, Sprague-Dawley

Type II diabetes mellitus (T2DM) is often accompanied by non-alcoholic steatohepatitis (NASH) and associated with hypercholesterolemia, that is, increased levels of plasma low-density lipoprotein (LDL) and oxidized LDL (ox-LDL). Approximately one-third of NASH develops hepatic fibrosis. The role of hypercholesterolemia in T2DM and NASH-associated hepatic fibrogenesis remains obscure. We previously reported that the phytochemical curcumin inhibited the activation of hepatic stellate cells (HSCs), the major effector cells during hepatic fibrogenesis, and protected the liver from fibrogenesis in vitro and in vivo. The aims of this study are to evaluate the role of ox-LDL in activation of HSCs, to assess curcumin effects on eliminating the role of ox-LDL, and to further explore the underlying mechanisms. In this report, we observe that ox-LDL alters the expression of genes closely relevant to HSC activation, which is eliminated by curcumin. Curcumin suppresses gene expression of lectin-like oxidized LDL receptor-1 (LOX-1), leading to the blockade of the transport of extracellular ox-LDL into cells. This suppressive effect of curcumin results from the interruption of Wnt signaling and the activation of peroxisome proliferator-activated receptor-gamma (PPARgamma). In conclusion, these results support our initial hypothesis and demonstrate that ox-LDL stimulates HSC activation, which is eliminated by curcumin by suppressing lox-1 expression by interrupting Wnt signaling and stimulating PPARgamma activity. These results provide novel insights into the role of ox-LDL in T2DM and NASH-associated hepatic fibrogenesis and mechanisms by which curcumin suppresses ox-LDL-induced HSC activation, as well as the implication of curcumin in the treatment of T2DM and NASH-associated hepatic fibrosis.

Topics: Animals; Blotting, Western; Coloring Agents; Curcumin; Diabetes Mellitus, Type 2; Gene Expression Regulation; Gene Silencing; Hepatic Stellate Cells; Hypercholesterolemia; Lipoproteins, LDL; Liver Cirrhosis; Male; Mutagenesis, Site-Directed; PPAR gamma; Rats; Rats, Sprague-Dawley; Receptors, Oxidized LDL

Topics: Breast Neoplasms; Curcumin; Exosomes; Female; Heat-Shock Proteins; Humans; Liver Cirrhosis; Neoplasms; Paracrine Communication

To investigate the molecular mechanism of the inhibitory effect of curcumine on the migration and invasion of hepatic stellate cells (HSC).. Rat hepatic stellate cells were cultured and activated with ConA. Matrix metalloproteinase-2 (MMP-2) expression and activity was determined by Western blot and gelatin zymography. Migration and invasion of HSC was assessed by wound healing assay and modified Boyden chamber assay.. Curcumine reduced the level and activity of MMP-2 expression in activated HSC in a dose-dependent manner. When treated with 25, 50 or 100 micromol/L curcumine, the expression of MMP-2 was reduced by 21.8%+/-5.1%, 65.5%+/-9.2% or 87.9%+/-11.5% (P < 0.05), and the activity of MMP-2 was also significantly reduced by curcumine. Migration and invasion of activated HSC was also inhibited by curcumine in a dose-dependent way. When treated with 25, 50 or 100 micromol/L curcumine, the migration of activated HSC was reduced by 27.5%+/-5.8%, 54.4%+/-7.6% or 67.1%+/-9.3% (P < 0.05), and the invasion of activated HSC was also significantly reduced by curcumine.. Curcumine inhibits migration and invasion of activated HSC by reducing MMP-2 expression and activity.

Topics: Animals; Blotting, Western; Cell Movement; Cells, Cultured; Concanavalin A; Curcumin; Dose-Response Relationship, Drug; Hepatic Stellate Cells; Liver Cirrhosis; Matrix Metalloproteinase 2; Rats; Tissue Inhibitor of Metalloproteinase-2

Topics: Animals; Apoptosis; Caspase 3; Cell Line; Cell Proliferation; Curcuma; Fas Ligand Protein; fas Receptor; Flow Cytometry; Hepatic Stellate Cells; Immunohistochemistry; Liver Cirrhosis; Plant Extracts; Plant Oils; Proto-Oncogene Proteins c-bcl-2; Rats; RNA, Messenger

We previously demonstrated that curcumin, a polyphenolic antioxidant purified from turmeric, up-regulated peroxisome proliferator-activated receptor (PPAR)-gamma gene expression and stimulated its signaling, leading to the inhibition of activation of hepatic stellate cells (HSC) in vitro. The current study evaluates the in vivo role of curcumin in protecting the liver against injury and fibrogenesis caused by carbon tetrachloride (CCl(4)) in rats and further explores the underlying mechanisms. We hypothesize that curcumin might protect the liver from CCl(4)-caused injury and fibrogenesis by attenuating oxidative stress, suppressing inflammation, and inhibiting activation of HSC. This report demonstrates that curcumin significantly protects the liver from injury by reducing the activities of serum aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase, and by improving the histological architecture of the liver. In addition, curcumin attenuates oxidative stress by increasing the content of hepatic glutathione, leading to the reduction in the level of lipid hydroperoxide. Curcumin dramatically suppresses inflammation by reducing levels of inflammatory cytokines, including interferon-gamma, tumor necrosis factor-alpha, and interleukin-6. Furthermore, curcumin inhibits HSC activation by elevating the level of PPARgamma and reducing the abundance of platelet-derived growth factor, transforming growth factor-beta, their receptors, and type I collagen. This study demonstrates that curcumin protects the rat liver from CCl(4)-caused injury and fibrogenesis by suppressing hepatic inflammation, attenuating hepatic oxidative stress and inhibiting HSC activation. These results confirm and extend our prior in vitro observations and provide novel insights into the mechanisms of curcumin in the protection of the liver. Our results suggest that curcumin might be a therapeutic antifibrotic agent for the treatment of hepatic fibrosis.

Topics: Animals; Antioxidants; Carbon Tetrachloride Poisoning; Curcumin; Inflammation; Liver; Liver Cirrhosis; Male; Oxidative Stress; Rats; Rats, Sprague-Dawley

The beneficial antioxidative, anti-inflammatory and antitumorigenic effects of curcumin have been well documented in relation to cancer and other chronic diseases. Recent evidence suggests that it may be of therapeutic interest in chronic liver disease. Hepatic fibrosis (scarring) occurs in advanced liver disease, where normal hepatic tissue is replaced with collagen-rich extracellular matrix and, if left untreated, results in cirrhosis. Curcumin inhibits liver cirrhosis in a rodent model and exerts multiple biological effects in hepatic stellate cells (HSCs), which play a central role in the pathogenesis of hepatic fibrosis. In response to liver injury, these cells proliferate producing pro-inflammatory mediators and extracellular matrix. Curcumin induces apoptosis and suppresses proliferation in HSCs. In addition, it inhibits extracellular matrix formation by enhancing HSC matrix metalloproteinase expression via PPARgamma and suppressing connective tissue growth factor (CTGF) expression. In this issue, Chen and co-workers propose that curcumin suppresses CTGF expression in HSC by inhibiting ERK and NF-kappaB activation. These studies suggest that curcumin modulates several intracellular signalling pathways in HSC and may be of future interest in hepatic fibrosis therapy.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Disease Models, Animal; Humans; Liver; Liver Cirrhosis; Signal Transduction

The function of peroxisome proliferator-activated receptor gamma (PPARgamma) in hepatic fibrogenesis remains largely unknown. Curcumin is a natural substance extracted form Curcuma Longa Linn and has a variety of pharmacological effects. In this study, the effects of curcumin on the proliferation, activation and apoptosis of rat hepatic stellate cells (HSCs) through PPARgamma signaling were investigated.. HSCs were isolated from the normal Sprague Dawley rats through in situ perfusion of the liver with Pronase E and density-gradient centrifugation with Nycodenz. Cells were treated with curcumin, troglitazone, salvianolic acid B or GW9662. The effect on HSCs proliferation was determined by MTT colorimetry. Total RNA was extracted by TRizol reagent and gene levels were determined by semi-quantitative RT-PCR. Total cellular and nuclear protein were isolated and separated by 10% sodium dodecy lsulfate polyacrylamide gel electrophoresis. Protein levels were determined by Western blot. Cell apoptosis was detected by Hoechst 33258 staining. PPARgamma subcellular distribution was detected by immunofluorescent staining. The activities of MMP-2 and 9 were measured by Gelatin zymograph assay.. Curcumin suppressed HSCs proliferation in a dose-dependent manner. As HSCs underwent gradual activation with culture prolongation the PPARgamma nuclear expression level decreased. Curcumin up-regulated PPARgamma expression and significantly inhibited the production of alpha-SMA and collagen I. PPARgamma is expressed in the cytoplasm and nucleus and is evenly distributed in HSCs, but accumulated in the nucleus of HSCs and disappeared from cytoplasm after curcumin treatment. Hoechst 33258 staining showed that curcumin induced the apoptosis of culture-activated HSCs and significantly increased pro-apoptotic Bax expression and reduced anti-apoptotic Bcl-2 expression. Cyclin D1 gene, activated NFkappaB p65 protein and TGFbetaR-I protein expression were down-regulated significantly by curcumin. The activities of MMP-2 and MMP-9 were enhanced significantly by curcumin.. Curcumin can inhibit the proliferation and activation of HSCs, induce the apoptosis of activated HSCs and enhance the activities of MMP-2 and MMP-9. The effects of curcumin are mediated through activating the PPARgamma signal transduction pathway and associated with PPARgamma nuclear translocation/redistribution.

Topics: Active Transport, Cell Nucleus; Activin Receptors, Type I; Animals; Apoptosis; bcl-2-Associated X Protein; Cell Nucleus; Cell Proliferation; Cells, Cultured; Curcumin; Cyclin D1; Liver; Liver Cirrhosis; Male; Matrix Metalloproteinase 9; PPAR gamma; Protein Serine-Threonine Kinases; Proto-Oncogene Proteins c-bcl-2; Rats; Rats, Sprague-Dawley; Receptor, Transforming Growth Factor-beta Type I; Receptors, Transforming Growth Factor beta; RNA, Messenger; Signal Transduction; Transcription Factor RelA

To study the effect of salvianolic acid B (SAB) and curcumin, the extracts of Salvia Miltiorrhiza and Curcuma Longa, on the proliferation and activation of hepatic stellate cell (HSC), and the extracellular signal regulated kinase (ERK) expression in it.. Rat's HSC-T6 were cultured and treated by SAB or curcumin. The inhibitory effect on cell proliferation was determined by 3-(4, 5-dimthyl-2-2thiazoly)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) colorimetry, and the expression levels of alpha smooth actin (alpha-SMA), collagen type I, and ERK were determined by Western blot.. SAB and curcumin inhibited the proliferation and activation of rat's HSC-T6 in dose-dependent fashion and significantly reduced the expression level of alpha-SMA (P < 0.01). Curcumin significantly reduced the expression of collagen type I (P < 0.05). Both SAB and curcumin showed insignificant effect on the ERK expression level, but they could significantly reduce the level of phosphorylated-ERK expression, showing significant difference as compared with that in the control group (P < 0.01 and P < 0.05 respectively).. SAB and curcumin could significantly inhibit the proliferation, activation of HSC, and the production of type I collagen in HSC, the mechanism may be associated with their inhibition on ERK phosphorylation.

Topics: Animals; Cell Division; Cell Line; Curcuma; Drugs, Chinese Herbal; Extracellular Matrix; Extracellular Signal-Regulated MAP Kinases; Hepatocytes; Liver Cirrhosis; MAP Kinase Signaling System; Phosphorylation; Plant Extracts; Rats; Salvia miltiorrhiza; Vasodilator Agents

Hepatic fibrosis is a result of an imbalance between enhanced matrix synthesis and diminished breakdown of connective tissue proteins, the net result of which is increased deposition of Extra Cellular Matrix. In this concept Matrix Metalloproteinases play an important role because their activity is largely responsible for extra cellular matrix breakdown. In the present study we have tested the influence of curcumin, the active principle of turmeric, on matrix metalloproteinase expression during alcohol and thermally oxidised sunflower oil induced liver toxicity. Male albino Wistar rats were used for the study. The matrix metalloproteinase expressions were found to be increased significantly in alcohol as well as thermally oxidised sunflower oil groups and on treatment with curcumin there was a significant decrease. In alcohol + thermally oxidised sunflower oil group, we found a significant decrease in matrix metalloproteinase activities. Administration of curcumin significantly improved their activities. From the results obtained, we could conclude that curcumin influences the hepatic matrix metalloproteinases and effectively protects liver against alcohol and delta PUFA induced toxicity.

Topics: Animals; Curcumin; Drug Interactions; Ethanol; Fatty Acids, Unsaturated; Liver; Liver Cirrhosis; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Oxidation-Reduction; Plant Oils; Rats; Sunflower Oil

To study the effects of rhizoma sparganii and radices zedoariae on hepatic fibrosis.. The rat immunohepatic fibrosis model was made by intraperitoneal injection of porcine serum and treated with rhizoma sparganii and radices zedoariae. The ALT, GGT, TP, ALb, A/G, IVC, LN, HA and the pathological change of the liver were observed.. Rhizoma sparganii and radices zedoariae could increase TP, ALb, A/G, decrease ALT, GGT, IVC, LN, HA and improve the pathological change.. Rhizoma sparganii and radices zedoariae can protect hepatic cells, alleviate degeneration and necrosis, recover structure and function, and reduce the proliferation of fibrous tissue.

Topics: Animals; Curcuma; Drugs, Chinese Herbal; Liver Cirrhosis; Magnoliopsida; Male; Phytotherapy; Plant Roots; Plants, Medicinal; Rats; Rats, Wistar; Rhizome