curcumin and Asthma

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; 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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; 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Atopic diseases (atopic dermatitis, asthma and allergic rhinitis) affects a huge number of people around the world and their incidence rate is on rise. Atopic dermatitis (AD) is more prevalent in paediatric population which sensitizes an individual to develop allergic rhinitis and asthma later in life. The complex pathogenesis of these allergic diseases though involves numerous cellular signalling pathways but redox imbalance has been reported to be critical for induction/perpetuation of inflammatory process under such conditions. The realm of complementary and alternative medicine has gained greater attention because of the reported anti-oxidant/anti-inflammatory properties. Several case studies of treating atopic diseases with homeopathic remedies have provided positive results. Likewise, pre-clinical studies suggest that various natural compounds suppress allergic response via exhibiting their anti-oxidant potential. Despite the reported beneficial effects of phytochemicals in experimental model system, the clinical success has not been documented so far. It appears that poor absorption and bioavailability of natural compounds may be one of the reasons for realizing their full potential. The current paper throws light on impact of phytochemicals in the redox linked cellular and signalling pathways that may be critical in manifestation of atopic diseases. Further, an effort has been made to identify the gaps in the area so that future strategies could be evolved to exploit the medicinal value of various phytochemicals for an improved efficiency.

Topics: Asthma; Catechols; Curcumin; Dermatitis, Atopic; Fatty Alcohols; Flavonoids; Ginsenosides; Humans; Hypersensitivity; Molecular Structure; Phytochemicals; Resveratrol

Vesicular systems like nanotechnology and liposomes are gaining tremendous attention lately in the field of respiratory diseases. These formulations enhance bioavailability of the drug candidate, which could be achieved through a novel drug delivery mechanism. Moreover, the therapeutic potential achieved through these systems is highly controllable over long durations of time providing better efficacy and patient compliance.. The objective of this paper is to review the recent literature on vesicular drug delivery systems containing curcumin.. We have collated and summarized various recent attempts made to develop different controlled release drug delivery systems containing curcumin which would be of great interest for herbal, formulation and biological scientists. There are several vesicular nanotechnological techniques involving curcumin which have been studied recently, targeting pulmonary diseases.. Different vesicular systems containing curcumin are being studied for their therapeutic potential in different respiratory diseases. There has been a renewed interest in formulations containing curcumin recently, primarily owing to the broad spectrum therapeutic potential of this miracle substance. Various types of formulations, containing curcumin, targeting different bodily systems have recently emerged and, nevertheless, the search for newer frontiers with this drug goes on.. This mini review, in this direction, tries to highlight the key research interventions employing vesicular systems of drug delivery with curcumin.

Topics: Asthma; Curcumin; Delayed-Action Preparations; Drug Compounding; Drug Delivery Systems; Humans; Liposomes; Nanomedicine; Nanoparticles; Pulmonary Disease, Chronic Obstructive; Respiration Disorders

The expression of NF-kappaB (NF-kappaB)-dependent pro-inflammatory genes in response to oxidative stress is regulated by the acetylation-deacetylation status of histones bound to the DNA. It has been suggested that in severe asthma and in chronic obstructive pulmonary disease (COPD) patients, oxidative stress not only activates the NF-kappaB pathway but also alters the histone acetylation and deacetylation balance via post-translational modification of histone deacetylases (HDACs). Corticosteroids have been one of the major modes of therapy against various chronic respiratory diseases such as asthma and COPD. Failure of corticosteroids to ameliorate such disease conditions has been attributed to their inability to either recruit HDAC2 or to the presence of an oxidatively modified HDAC2 in asthmatics and COPD subjects. Naturally occurring polyphenols such as curcumin and resveratrol have been increasingly considered as safer nutraceuticals. Curcumin is a polyphenol present in the spice turmeric, which can directly scavenge free radicals such as superoxide anion and nitric oxide and modulate important signaling pathways mediated via NF-kappaB and mitogen-activated protein kinase pathways. Polyphenols also down-regulate expression of pro-inflammatory mediators, matrix metalloproteinases, adhesion molecules, and growth factor receptor genes and they up-regulate HDAC2 in the lung. Thus, curcumin may be a potential antioxidant and anti-inflammatory therapeutic agent against chronic inflammatory lung diseases.

Topics: Anti-Inflammatory Agents; Antioxidants; Asthma; Curcumin; Gene Expression; Glucocorticoids; Humans; Inflammation; NF-kappa B; Pulmonary Disease, Chronic Obstructive; Signal Transduction; Steroids

Recent years have witnessed a global increase in allergy and asthma, particularly in developed countries. Attempts to develop effective control measures for allergy and asthma resulted in the exploration of alternate medicines including herbal remedies traditionally used in old world countries. Turmeric is known for its multiple health restoring properties, and has been used in treating several diseases including several respiratory disorders. Turmeric is a common spice used in the culinary preparations in South and East Asian countries. The active component of turmeric is curcumin, a polyphenolic phytochemical, with anti-inflammatory, antiamyloid, antiseptic, antitumor, and antioxidative properties. Curcumin was reported to have antiallergic properties with inhibitory effect on histamine release from mast cells. The effectiveness of curcumin in allergy and asthma has been further investigated using a murine model of allergy. The results indicate a marked inhibition of allergic response in animals treated with curcumin suggesting a major role for curcumin in reducing the allergic response. The present review focuses on the results of research aimed to understand the immunomodulation induced by curcumin and its associated roles in the amelioration of allergy. These findings needed further evaluation, extrapolation, and confirmation before using curcumin for controlling allergy and asthma in humans.

Topics: Acquired Immunodeficiency Syndrome; Animals; Asthma; Curcumin; Disease Models, Animal; Egypt; Humans; Hypersensitivity; Immunologic Factors; India; Latex Hypersensitivity; Medicine, Traditional; Plant Roots

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; 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Curcumin, a derivative of the spice turmeric, has been adopted by Eastern medicine for centuries as an adjunct to treat several medical conditions (e.g., anorexia and arthritis) because of its well-established anti-inflammatory properties. Studies have shown that the use of curcumin in mice models has led to reduction in several inflammatory markers as well as key inflammatory pathway enzymes. As a result, studies in Western medicine have developed to determine if this recognized benefit can be utilized for patients with inflammatory lung diseases, such as asthma. This study will seek to better understand if curcumin can be used as an adjunctive therapy for improving asthma control of patients with moderate to severe asthma; a finding we hope will allow for a more affordable treatment.. This study will utilize a randomized, placebo controlled, double blinded pilot superiority phase 2 trial at an outpatient pulmonary clinic in Southern California, USA. Subjects will be receiving Curcumin 1500 mg or matching placebo by mouth twice daily for the study period of 12 weeks. Subjects will be randomized to either a placebo or intervention Curcumin. Subjects will have 6 clinic visits: screening visit, a baseline visit, monthly clinic visits (weeks 4, 8, and 12), at weeks 4, 8, and a follow-up clinic visit or phone-call (week 16). Changes in asthma control test scores, number of days missed from school/work, FEV1 (% predicted), FEV1/FVC ratio, FVC (% predicted), blood eosinophil count, blood total IgE, and FeNO levels will be compared by group over time.. The therapeutic effects of curcumin have been studied on a limited basis in asthmatics and has shown mixed results thus far. Our study hopes to further establish the benefits of curcumin, however, there are potential issues that may arise from our study design that we will address within this paper. Moreover, the onset of the COVID-19 pandemic has resulted in safety concerns that have delayed initiation of our study. This study will contribute to existing literature on curcumin's role in reducing lung inflammation as it presents in asthmatics as well as patients suffering from COVID-19.. This study protocol has been approved by the Institutional Review Board at Loma Linda University Health, (NCT04353310). IND# 145101 Registered April 20th, 2020. https://clinicaltrials.gov/ct2/show/NCT04353310 .

Topics: Administration, Oral; Adult; Ambulatory Care; Anti-Inflammatory Agents, Non-Steroidal; Antioxidants; Asthma; Clinical Trials, Phase II as Topic; COVID-19; COVID-19 Drug Treatment; Curcumin; Double-Blind Method; Drug Monitoring; Eosinophils; Female; Humans; Immunoglobulin E; Leukocyte Count; Male; Randomized Controlled Trials as Topic; SARS-CoV-2; Severity of Illness Index

Roots of Curcuma longa L. are used as medicine for millennia. They possess several pharmacological properties, including anti-inflammatory action, and can be suitable for asthma treatment.. We aimed to test the hypothesis that, in children and adolescents with persistent asthma, the administration of powdered roots of C. longa for 6 months, in addition to standard treatment, compared to placebo, will result in better disease control.. We conducted a randomized, double-blind, placebo-controlled, phase II clinical trial. Patients were randomly assigned to receive 30 mg/kg/day of C. longa for 6 months, or placebo. Data were collected prospectively. All patients were categorized for asthma severity and control according to GINA-2016 and underwent pulmonary function tests.. Overall, both groups experienced amelioration of their frequency of symptoms and interference with normal activity, but no differences were found between the two treatment groups. However, patients receiving C. longa experienced less frequent nighttime awakenings, less frequent use of short-acting β-adrenergic agonists, and better disease control after 3 and 6 months.. The powdered roots of C. longa led to less frequent nighttime awakenings, less frequent use of short-acting β-adrenergic agonists, and better disease control after 3 and 6 months, when compared to placebo.

Topics: Adolescent; Asthma; Child; Curcuma; Curcumin; Diarylheptanoids; Double-Blind Method; Humans; Phytotherapy; Plant Roots; Powders

Histone deacetylase inhibitors (HDACi) are novel class of drugs as they are involved in post translational modification of several proteins involved in signaling pathways related to asthma. HDACi have been reported to elicit protective effects on asthma but the signaling pathways associated with it have not been investigated much. Recently, we have demonstrated that intranasal administrations of Pan-HDAC inhibitors, sodium butyrate and curcumin, which have effectively reduced asthma severity via HDAC1 inhibition in Ovalbumin induced mouse model. Present study aimed to investigate possible pathways by which curcumin and sodium butyrate may minimize asthma pathogenesis via HDAC 1 inhibition. Balb/c mice were exposed (sensitized and challenged) with Ovalbumin to establish allergic asthma model followed by pretreatment of curcumin (5 mg/kg) and sodium butyrate (50 mg/kg) through intranasal route. Effects of curcumin and sodium butyrate on HIF-1α/VEGF signaling through activation of PI3K/Akt axis has been investigated using protein expressions followed by chromatin immunoprecipitation of BCL2 and CCL2 against HDAC1. Molecular docking analysis was also performed to investigate effects of curcumin and butyrate on mucus hypersecretion, goblet cell hyperplasia and airway hyperresponsiveness. Augmented expressions of HDAC-1, HIF-1α, VEGF, p-Akt and p-PI3K were observed in asthmatic group which was suppressed in both the treatments. NRF-2 level was significantly restored by curcumin and butyrate treatments. Protein expressions of p-p38, IL-5 and mRNA expressions of GATA-3 were also reduced in curcumin and butyrate treatment groups. Our findings suggest that curcumin and sodium butyrate may attenuate airway inflammation via down regulation of p-Akt/p-PI3K/HIF-1α/VEGF axis.

Topics: Animals; Antioxidants; Asthma; Butyric Acid; Curcumin; Histone Deacetylase Inhibitors; Mice; Molecular Docking Simulation; Ovalbumin; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Vascular Endothelial Growth Factor A

Bronchoconstriction, along with inflammation and hyperresponsiveness is the characteristic feature associated with asthma, contributing to variable airflow obstruction, which manifests shortness of breath, cough and wheeze, etc. Histone deacetylases 8 (HDAC8) is the member of class I HDAC family and known to regulate microtubule integrity and muscle contraction. Therefore, we aimed to investigate the effects of HDAC8 inhibition in murine model of asthma using Pan-HDAC inhibitor curcumin (CUR) and HDAC8-specific inhibitor PCI-34051 (PCI), alone and in combination.. To develop asthmatic mouse model, Balb/c mice were sensitized and challenged with ovalbumin (OVA). CUR (10 mg/kg, pre, post, alone and combined treatment) and PCI (0.5 mg/kg), were administered through intranasal (i.n) route, an hour before OVA aerosol challenge. Effects of HDAC8 inhibition by CUR and PCI pretreatments were evaluated in terms of inflammation, oxidative stress and fibrosis markers. Efficacy of curcumin post-treatment (CUR(p)) was also evaluated simultaneously.. Inflammatory cell recruitment, oxidative stress (reactive oxygen species, nitric oxide), histamine and Immunoglobulin E (IgE) levels and expression of fibrosis markers including hydroxyproline, matrix metalloproteinases-9 and alpha smooth muscle actin (MMP-9 and α-SMA) were significantly reduced by CUR, CUR(p), PCI-alone and combined treatments. Protein expressions of HDAC8, Nuclear factor-κB (NF-κB) accompanied by MAPKs (mitogen-activated protein kinases) were significantly reduced by the treatments. Structural alterations were examined by histopathological analysis and linked with the fibrotic changes.. Present study indicates protective effects of HDAC8 inhibition in asthma using HDAC8 using CUR and PCI alone or in combination, attenuates airway inflammation, fibrosis and remodeling; hence, bronchoconstriction was accompanied through modulation of MAP kinase pathway.

Topics: Animals; Asthma; Curcumin; Disease Models, Animal; Fibrosis; Inflammation; Lung; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases; Ovalbumin

Asthma being an inflammatory disease of the airways lead to structural alterations in lungs which often results in the severity of the disease. Curcumin, diferuloylmethane, is well known for its medicinal properties but its anti-inflammatory potential via Histone deacetylase inhibition (HDACi) has not been revealed yet. Therefore, we have explored here, anti-inflammatory and anti-fibrotic potential of intranasal curcumin via HDAC inhibition and compared its potential with Sodium butyrate (SoB), a known histone deacetylase inhibitor of Class I and II series. Anti-inflammatory potential of SoB, has been investigated in cancer but not been studied in asthma before.. In present study, ovalbumin (OVA) was used to sensitize Balb/c mice and later exposed to (1%) OVA aerosol. Curcumin (5 mg/kg) and Sodium butyrate (50 mg/kg) was administered through intranasal route an hour before OVA aerosol challenge. Efficacies of SoB and Curcumin as HDAC inhibitors were evaluated in terms of different inflammatory parameters like, total inflammatory cell count, reactive oxygen species (ROS), histamine release, nitric oxide and serum IgE levels. Inflammatory cell recruitment was analyzed by H&E staining and structural alterations were revealed by Masson's Trichrome staining of lung sections.. Enhanced Matrix Metalloproteinase-2 and 9 (MMP-2 and MMP-9) activities were observed in bronchoalveolar lavage fluid (BALF) of asthmatic mice by gelatin zymography which was inhibited in both treatment groups. Protein expressions of MMP-9, HDAC 1, H3acK9 and NF-kB p65 were modulated in intranasal curcumin and SoB pretreatment groups.. This is the first report where intranasal curcumin inhibited asthma severity via affecting HDAC 1 (H3acK9) leading to NF-kB suppression in mouse model of allergic asthma.

Topics: Administration, Intranasal; Animals; Anti-Inflammatory Agents; Asthma; Bronchoalveolar Lavage Fluid; Butyric Acid; Curcumin; Disease Models, Animal; Fibrosis; Histone Deacetylase Inhibitors; Immunoglobulin E; Inflammation; Lung; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Mice; Mice, Inbred BALB C; Ovalbumin

The inflammasome NOD-like receptor (NLR) family, the pyrin domain containing 3 (NLRP3) is closely associated with exacerbation of asthma as endotoxin (lipopolysaccharide, LPS) is one of its activators present in the environment. Present study is undertaken to investigate anti-inflammatory effects of a well known phytochemical, curcumin, which might regulate LPS exposed asthma exacerbations by modulating NLRP3 activation if given through intranasal route. Balb/c mice were sensitized with intraperitoneal injection of OVA (Ovalbumin; 100 μg of OVA with alum) from day 1 to 8 and exposed to LPS with 1% OVA aerosol from day 9 to 15. LPS (0.1 μg) was given an hour before sensitization and OVA-aerosol challenge. Significant decrease in inflammatory cell recruitment and restoration of structural changes in lungs, alterations in mRNA and protein expressions of TLR-4, NF-κB, NLRP3, Caspase-1, IL-1β, MMP-9, IL-5 and IL-17 in intranasal curcumin alone and corticosteroid combined pretreatment group.

Topics: Administration, Intranasal; Animals; Asthma; Caspase 1; Curcumin; Dexamethasone; Inflammasomes; Interleukin-1beta; Lipopolysaccharides; Lung; Mice; Mice, Inbred BALB C; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Ovalbumin; Transcription Factor RelA

2,6-Bis-(4-hydroxyl-3-methoxybenzylidine) cyclohexanone (BHMC), a synthetic curcuminoid analogue, has been shown to exhibit anti-inflammatory properties in cellular models of inflammation and improve the survival of mice from lethal sepsis. We further evaluated the therapeutic effect of BHMC on acute airway inflammation in a mouse model of allergic asthma. Mice were sensitized and challenged with ovalbumin (OVA), followed by intraperitoneal administration of 0.1, 1, and 10 mg/kg of BHMC. Bronchoalveolar lavage fluid, blood, and lung samples were collected, and the respiratory function was measured. OVA sensitization and challenge increased airway hyperresponsiveness (AHR) and pulmonary inflammation. All three doses of BHMC (0.1-10 mg/kg) significantly reduced the number of eosinophils, lymphocytes, macrophages, and neutrophils, as well as the levels of Th2 cytokines (IL-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF) as compared to OVA-challenged mice. However, serum level of IgE was not affected. All three doses of BHMC (0.1-10 mg/kg) were effective in suppressing the infiltration of inflammatory cells at the peribronchial and perivascular regions, with the greatest effect observed at 1 mg/kg which was comparable to dexamethasone. Goblet cell hyperplasia was inhibited by 1 and 10 mg/kg of BHMC, while the lowest dose (0.1 mg/kg) had no significant inhibitory effect. These findings demonstrate that BHMC, a synthetic nonsteroidal small molecule, ameliorates acute airway inflammation associated with allergic asthma, primarily by suppressing the release of inflammatory mediators and goblet cell hyperplasia to a lesser extent in acute airway inflammation of allergic asthma.

Topics: Acute Disease; Animals; Asthma; Bronchial Hyperreactivity; Curcumin; Cyclohexanones; Cytokines; Goblet Cells; Immunoglobulin E; Leukocytes; Male; Mice; Mice, Inbred BALB C; Ovalbumin

Dietary factors can reshape the gut microbiota and consequently affect disease progression. We previously reported that tetrahydrocurcumin (THC), the major active metabolite of curcumin (Cur), could ameliorate allergic inflammation in asthmatic mice. Herein, we aimed to investigate whether THC or Cur exerts anti-inflammatory effects on allergic asthma via modulating gut microbiota. Ovalbumin (OVA)-induced asthmatic mice were treated with Cur or THC, and the gut microbiota profiles were analyzed by 16S rRNA sequencing. Fecal microbiota transplantation (FMT) from Cur- or THC-fed donor mice was administered to OVA-induced asthmatic mice. Nasal symptoms and inflammation patterns of lungs and colons were evaluated in control, OVA-induced and Cur-or THC-treated mice. Both Cur and THC treatment could alter the compositions of the gut microbiota in asthmatic mice, characterized by a significant decrease in the ratio of Firmicutes to Bacteroidetes; Cur or THC supplementation also reduced the relative abundances of pro-inflammatory bacteria, e.g., Proteobacteria, Intestinimonas, Unidentified-Ruminococcaceae, and Lachnospiraceae, in OVA-induced mice. The relative abundances of Unidentified-Ruminococcaceae, Romboutsia, Intestinimonas, Akkermansia, and Mucispirillum were positively associated with the levels of Th2-related factors in asthmatic mice upon Cur or THC treatment. Moreover, THC-FMT showed better preventive effects than Cur-FMT on the development of allergic inflammation in OVA-induced mice, resulting in a reduction in symptoms and Th2-mediated inflammation in both lung and colon tissues. The results reveal that Cur- or THC-mediated alleviation of airway allergic inflammation is dependent on gut microbiota modulation. THC-induced gut microbiota may have therapeutic potential for asthma treatment.

Topics: Animals; Asthma; Curcumin; Female; Gastrointestinal Microbiome; Inflammation; Lung; Mice; Mice, Inbred BALB C

Curcumin, extracted from the roots of Curcuma longa, has been used as an anti-inflammatory agent since the time of Ayurveda. The present work was designed to evaluate the potential of curcumin in amelioration of ovalbumin (OVA) induced AD in mice. Female BALB/c mice were subjected to skin OVA-patch application for a period of 1 week followed by resting period of 2 weeks, and the same protocol was repeated thrice. Curcumin was administered daily at dose of 20 mg/kg (i.p.) for 7 consecutive days during last sensitization phase. The phytochemical ameliorated the OVA-induced skin pathology as evident by normalization of epidermal thickness and suppressed infiltration of inflammatory cells in dermal region. The expression of Th2 promoting cytokines (TSLP/IL-33) and Th2 cytokines (IL-4/IL-5/IL-13/IL-31) was suppressed markedly along with reduced STAT-6 phosphorylation and GATA-3 expression. Curcumin administration also restored the redox balance and phosphorylation status of P65-NF-κB. Additionally, the epicutaneously sensitized mice challenged with aerosolized OVA developed asthmatic features which were effectively thwarted back upon curcumin treatment as reflected by data on total/differential cells in BALF and mRNA expression of Th2 cytokines in lungs. Overall, our findings demonstrate that curcumin treatment blunts the development of AD as well as associated atopic march in experimental mice.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Curcumin; Cytokines; Dermatitis, Atopic; Disease Models, Animal; Disease Progression; Female; GATA3 Transcription Factor; Lung; Mice, Inbred BALB C; Ovalbumin; Phosphorylation; Skin; STAT6 Transcription Factor; Th2 Cells; Transcription Factor RelA

Tetrahydrocurcumin (THC) is the major active metabolite of curcumin, which is a dietary factor derived from Curcuma species. Our previous study demonstrated a significant beneficial effect of THC in mice with allergic asthma. Glucocorticosteroids (GCs) are commonly used drugs in asthma. Whether THC supplementation could promote the beneficial effects of GC therapy on asthma has not yet been reported. The current study aimed to investigate the combined efficacy of GC and THC treatment in a mouse model of allergic asthma.. BALB/c mice were randomly divided into 5 groups: the control group, ovalbumin (OVA)-induced group, and OVA-induced mice treated with dietary THC only, intraperitoneal injection of dexamethasone (DEX) only, or THC combined with DEX. The nasal symptoms, histopathological alterations of lung tissues, lung cytokine production, and Th cell subsets were assessed.. THC or DEX had beneficial effects on nasal symptoms and pathological lung changes, and the therapeutic effects between THC and DEX treatment were comparable. Importantly, compared to the monotherapy groups (THC or DEX only), the combination of THC and DEX showed a significantly reduced nasal rubbing frequency, lower mucus hyperproduction, lower Th2 and Th17 cell numbers as well as lower related cytokine levels (IL-4, IL-5, and IL-17A).. Supplementation with THC can enhance the therapeutic effects of DEX to alleviate airway symptoms, lung inflammation, and the Th2 response. Our findings suggest that dietary administration of THC could act as an add-on therapy for asthma treated with GCs.

Topics: Allergens; Animals; Anti-Asthmatic Agents; Asthma; Curcuma; Curcumin; Dexamethasone; Dietary Supplements; Disease Models, Animal; Female; Humans; Mice; Mice, Inbred BALB C; Ovalbumin; Th2 Cells

Topics: Asthma; Curcumin; Humans; Liposomes; Particle Size; RNA, Messenger

Curcumin is well known for possessing anti-inflammatory properties and for its beneficial effects in the treatment of asthma. Current study investigates the immunomodulatory and anti-inflammatory effects of curcumin using mouse model of ovalbumin-induced allergic asthma. BALB/c mice were immunized with ovalbumin on day 0 and 14 to induce allergic asthma. Animals were treated with two different doses of curcumin (20 mg/kg and 100 mg/kg) and methylprednisolone from day 21 to 28. Mice were also daily challenged intranasally with ovalbumin during treatment period, and all groups were sacrificed at day 28. Histopathological examination showed amelioration of allergic asthma in treated groups as evident by the attenuation of infiltration of inflammatory cells, goblet cell hyperplasia, alveolar thickening, and edema and vascular congestion. Curcumin significantly reduced total and differential leukocyte counts in both bronchoalveolar lavage fluid and blood. Reverse transcription polymerase chain reaction analysis showed significantly suppressed mRNA expression levels of IL-4 and IL-5 (pro-inflammatory cytokines), TNF-α, TGF-β (pro-fibrotic cytokines), eotaxin (chemokine), and heat shock protein 70 (marker of airway obstruction) in treated groups. Attenuation of these pro-inflammatory markers might have led to the suppression of airway inflammation. The expression levels of aquaporin-1 (AQP) and AQP-5 were found significantly elevated in experimental groups which might be responsible for reduction of pulmonary edema. In conclusion, curcumin significantly ameliorated allergic asthma. The anti-asthmatic effect might be attributed to the suppression of pro-inflammatory cytokines, and elevation of aquaporin expression levels, suggesting further studies and clinical trials to establish its candidature in the treatment of allergic asthma.

Topics: Albumins; Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Aquaporin 1; Aquaporin 5; Aquaporins; Asthma; Curcumin; Cytokines; Immunologic Factors; Mice; Pulmonary Edema

Allergic asthma and atherosclerosis represent different directions of inflammatory responses of CD4. We aimed to investigate the roles of curcumin in asthma-accelerated atherosclerosis plaque formation, and the change of CD4. Six to eight-week-old apolipoprotein E. The accelerated atherosclerosis was induced by allergic asthma accompanied by increased T helper cell (Th)2 and Th17 cells and decreased regulatory T cells (Tregs) in the spleen. After the 8-week treatment with curcumin, the lesion areas in the aortic root in asthmatic mice significantly improved, and the elevated Th2 and Th17 cells significantly decreased, but Tregs markedly increased. Although curcumin treatment markedly reduced the interleukin (IL)-4 and IL-13 in serum and spleen, the elevated IL-17A did not decrease. Moreover, Th1 cells showed no significant change between different groups. The mRNA expression levels of M1 macrophage-related inflammatory factors IL-6, iNOS and IL-1β were markedly elevated in the spleens of asthmatic mice, but significantly decreased after the 8-week treatment with curcumin.. Curcumin ameliorated the aggravation of atherosclerotic lesions and stabilised plaque by modulating the balance of Th2/Tregs in asthmatic apoE

Topics: Animals; Asthma; Atherosclerosis; Curcumin; Interleukins; Mice; Mice, Inbred C57BL; Mice, Knockout, ApoE; Ovalbumin; Plaque, Atherosclerotic; T-Lymphocytes, Regulatory; Th1 Cells; Th17 Cells; Th2 Cells

The accumulation of airway apoptotic cells may be an important factor causing airway hyper-responsiveness (AHR). Whether the apoptotic cells can be promptly removed is related to the occurrence and course of asthma. In recent years, studies have shown that Rac1 is involved in many cellular biological activities including the formation and elimination of apoptotic cells. In this study, based on the analysis of airway local cells and related factors in asthmatic mice, we evaluated the expression of Rac1 in airway epithelial cells or phagocytes and analysed its relationship with the incidence of apoptosis or scavenging of apoptotic cells. Our data showed that the expression level of Rac1 in asthmatic mice decreased significantly, while the expression of IL-33 increased obviously. The airway epithelial cell line was stimulated by curcumin at 50 μmol/L for 24-48 hours; more than 50% of the cells were apoptotic, and of which, about 20% were late apoptosis. Rac1 inhibitor (NSC23766) can enhance the apoptosis effect. In addition, the ability of phagocytosis and migration in the epithelial cells or macrophages was increased following the application of Rac1 inhibitors or specific siRNA in a dose-dependent manner, and the expression level of IL-33 was simultaneously increased after blocking Rac1. It is suggested that the down regulation of Rac1 in asthma may contribute to the apoptosis of airway epithelial cells and affect the clearance of apoptotic cells, which will lead to the aggregation of the apoptotic cells in the respiratory tract and participate in AHR.

Topics: A549 Cells; Aminoquinolines; Animals; Apoptosis; Asthma; Bronchial Hyperreactivity; Curcumin; Down-Regulation; Female; Humans; Mice; Mice, Inbred BALB C; Phagocytes; Phagocytosis; Pyrimidines; rac1 GTP-Binding Protein; Respiratory Hypersensitivity; Respiratory Mucosa; RNA, Small Interfering

Asthma is characterized by airway inflammation and mucus hypersecretion. Curcumin possessed a potent anti-inflammatory property involved in the PPAR

Topics: Animals; Asthma; Blotting, Western; Cell Line; Curcumin; Humans; Interleukin-13; Interleukin-4; Interleukin-5; Male; Mice; Mice, Inbred BALB C; NF-kappa B; Ovalbumin; PPAR gamma; RNA, Small Interfering; Signal Transduction; Tumor Necrosis Factor-alpha

Allergic asthma is an inflammatory condition accompanied by inflammation as well as oxidative stress. Supplementation of an anti-inflammatory agent having antioxidant properties may have therapeutic effects against this disease. Over the recent decades, the interest in combination therapy as new alternative medication has increased and it offers numerous benefits along with noticeable lack of toxicity as well as side effects. In this study, protective effects of curcumin alone and in combination with piperine were evaluated in mouse model of allergic asthma. Balb/c mice were sensitized on days 0, 7, and 14 and challenged from days 16-30 on alternate days with ovalbumin (OVA). Mice were pretreated with curcumin (Cur; 10 and 20 mg/kg) and piperine (Pip; 5 mg/kg) alone and in combination via the intraperitoneal route on days 16-30 and compared with intranasal curcumin (5 mg/kg) treatment. Blood, bronchoalveolar lavage fluid (BALF), and lungs were collected after mice were sacrificed on day 31st. Mice immunized with OVA have shown significant increase in airway inflammation and oxidative stress as determined by oxidative stress markers. A significant suppression was observed with all the treatments, but intranasal curcumin treatment group has shown maximum suppression. So, among all the treatment strategies utilized, intranasal curcumin administration was most appropriate in reducing inflammation and oxidative stress and possesses therapeutic potential against allergic asthma. Present study may prove the possibility of development of curcumin nasal drops towards treatment of allergic asthma.

Topics: Alkaloids; Animals; Anti-Inflammatory Agents; Asthma; Benzodioxoles; Bronchoalveolar Lavage Fluid; Curcumin; Drug Administration Routes; Drug Therapy, Combination; Inflammation; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Oxidative Stress; Piperidines; Polyunsaturated Alkamides

Curcumin has shown various pharmacological effects such as anti-inflammatory activities. In this study, the effects of curcumin on tracheal responsiveness and lung pathological features were evaluated in a rat model of asthma.. Tracheal responsiveness and lung pathological features were evaluated in control rats (C), ovalbumin (OVA)-sensitized rats (as an animal model of asthma; A), A rats treated with curcumin (Cu, 0.15, 0.30, and 0.60mg/ml) and dexamethasone (D, 1.25μg/ml), (n=8 in curcumin-treated groups and n=6 in other groups). Curcumin and dexamethasone were added to animals' drinking water during the sensitization period.. Asthmatic group showed increased lung pathological score and tracheal responsiveness to methacholine and OVA compared to control group (p<0.01 to p<0.001). Pathological features including interstitial inflammation, interstitial fibrosis, bleeding, and emphysema as well as tracheal responsiveness to methacholine and OVA, were significantly decreased in treated groups with dexamethasone and all concentrations of curcumin compared to group A (p<0.05 to p<0.001). Epithelial damage was also significantly decreased in treated groups with the two higher concentrations of curcumin (p<0.05 to p<0.001).. Curcumin showed preventive effects on tracheal responsiveness and lung pathological features in asthmatic rats.

Topics: Animals; Asthma; Curcumin; Dexamethasone; Dose-Response Relationship, Drug; Isometric Contraction; Lung; Male; Methacholine Chloride; Ovalbumin; Rats; Trachea

Curcumin a component of turmeric, which is derived from Curcuma longa is used as a colouring agent and as a dietary spice for centuries. Extensive studies have been done on the anti-inflammatory activity of curcumin along with its molecular mechanism involving different signalling pathways. However, the physicochemical and biological properties such as poor solubility and rapid metabolism of curcumin have led to low bioavailability and hence limits its application. Current therapies for asthma such as bronchodilators and inhaled corticosteroids (ICS) are aimed at controlling disease symptoms and prevent asthma exacerbation. However, this approach requires lifetime therapy and is associated with a constellation of side effects. This creates a clear unmet medical need and there is an urgent demand for new and more-effective treatments. The present study is aimed to formulate liposomes containing curcumin and evaluate for its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation on BCi-NS1.1 cell line. Curcumin and salbutamol liposomes were formulated using lipid hydration method. The prepared liposomes were characterized in terms of particle size, zeta potential, encapsulation efficiency and in-vitro release profile. The liposomes were tested on BCI-NS1.1 cell line to evaluate its anti-inflammatory properties. The various pro-inflammatory markers studied were Interleukin-6 (IL-6), Interleukin-8 (IL-8), Interleukin-1β (IL-1β) and Tumour Necrosis Factor-a (TNF-a). Additionally, molecular mechanics simulations were used to elucidate the positioning, energy minimization, and aqueous dispersion of the liposomal architecture involving lecithin and curcumin. The prepared curcumin formulation showed an average size and zeta potential of 271.3 ± 3.06 nm and -61.0 mV, respectively. The drug encapsulation efficiency of liposomal curcumin is 81.1%. Both curcumin-loaded liposomes formulation (1 μg/mL, 5 μg/mL) resulted in significant (p < 0.05) reduction in the level of pro-inflammatory marker expression such as IL-6, IL-8, IL-1β and TNF-a compared to positive control group. Liposomal curcumin with the dose of 1 μg/mL reduced the inflammatory markers more effectively compared to that of 5 μg/mL. Liposomal curcumin could be a promising intervention for asthma therapy showing their efficacy in suppressing the important pro-inflammatory markers involved in the pathogenesis of asthma.

Topics: Asthma; Biomarkers; Cell Line; Computer Simulation; Curcumin; Drug Liberation; Humans; Inflammation; Liposomes; Models, Molecular; Particle Size; Spectroscopy, Fourier Transform Infrared; Static Electricity

Curcumin (Cur), derived from Curcuma species, exhibits anti-inflammatory, antioxidant, and anticancer effects. Although Cur has some beneficial effects on asthma, its clinical application is limited by its low bioavailability. Tetrahydrocurcumin (THC), the major active metabolite of Cur, has multiple biological functions, similarly to Cur, and importantly, it showed enhanced bioavailability in tissues and plasma. However, the effect of THC on asthma has not been reported.. The current study sought to investigate the efficacy of dietary THC on allergic asthma compared to that of Cur in an animal model.. The anti-inflammatory effects of Cur and THC were evaluated in an ovalbumin-induced asthmatic mouse model. The nasal symptoms, pathological alterations of the lung tissues, oxidants and antioxidants, cytokine production, T cell subsets, and Th2-related signalling pathway activity were assessed.. Both THC and Cur had beneficial effects on asthmatic mice with regard to nasal symptoms, pathological changes (eosinophils and mucus hyper-production), oxidative stress (malondialdehyde), cytokine production (IL-13), Th17 and cytotoxic T cell subsets, and Th2 signalling pathway (IL-4Rα-Jak1-STAT6 and Jagged1/Jagged2-Notch1/Notch2 axis) activity. THC was more effective than Cur in suppressing tissue eosinophilia, mucus production, and IL-4Rα/Jak1/STAT6 pathway activity. Furthermore, only THC inhibited peripheral eosinophil levels, Th2 cytokines (IL-4 and IL-5), and Th2 cell subsets and enhanced an antioxidant enzyme (glutathione).. The above results demonstrated for the first time that THC was superior to Cur in modulating allergic asthmatic phenotypes, especially attenuating the Th2 response. THC might be a potentially effective agent for asthma treatment.

Topics: Allergens; Animals; Asthma; Biomarkers; Curcumin; Cytokines; Disease Models, Animal; Female; Inflammation Mediators; Jagged-1 Protein; Jagged-2 Protein; Janus Kinase 1; Leukocytes; Mice; Oxidative Stress; Receptor, Notch1; Receptor, Notch2; Receptors, Cell Surface; Signal Transduction; STAT6 Transcription Factor; Th2 Cells

Curcumin, a natural product found in the plant Curcuma longa, has been reported to have diverse range of molecular targets that influence numerous biochemical and molecular cascades including anti-inflammatory and antioxidant properties.. The aim of the study was to investigate the therapeutic potential of intranasal curcumin on ovalbumin (OVA)-induced chronic asthma and to elucidate underlying molecular mechanisms.. Mice were sensitized and exposed to 2% OVA aerosol for 2 times in a week for five consecutive weeks to study effect of intranasal curcumin on various MAPK pathway enzymes involved in chronic asthma and its effect on the activation of nuclear factor kB (NF-kB).. Curcumin treatment decreased the ROS level in BALF and nitrite level in blood serum of chronic asthmatic mice. Curcumin treatment had significantly decreased the phosphorylation of JNK, ERK1/2, and p38 and COX-2 expression thereby nuclear factor κB (NF-κB) activation and expression in lung tissues.. These results suggest that intranasal curcumin protects against asthma via action on mitogen-activated protein kinase (MAPK)/NF-κB signaling pathways.

Topics: Administration, Intranasal; Animals; Asthma; Curcuma; Curcumin; Cyclooxygenase 2; Lung; Mice; Mice, Inbred BALB C; Mitogen-Activated Protein Kinases; NF-kappa B; Ovalbumin; Phosphorylation; Signal Transduction

Asthma is a chronic inflammatory, heterogeneous airway disease affecting millions of people around the world. Curcumin has been found to have anti-inflammatory and antifibrosis effects. Researchers reported that curcumin regulated Wnt/β-catenin signaling in lots of cells. However, whether curcumin regulates the levels of Wnt/β-Catenin signaling in lung tissues and DCs (dendritic cells) remains unclear. In this study, we assessed the effects of curcumin on DCs and asthma.. C57BL/6 mice immunized with OVA (ovalbumin) were challenged thrice with an aerosol of OVA every second day for 8 days. Dexamethasone or curcumin was administered intraperitoneally to OVA-immunized C57BL/6 mice on day 24 once a day for 9 days. Mice were analyzed for effects of curcumin on asthma, inflammatory cell infiltration and cytokine levels in lung tissue. DCs were isolated from mouse bone morrow. The surface markers CD40, CD86 and CD11c of DCs was detected by FACS (fluorescence activated cell sorting) and the function of DCs was detected by mixed lymphocyte reaction. The expression of GSK-3β and β-catenin was detected by Western Blot.. Results showed that OVA increased the number of inflammatory factors in BALF (bronchoalveolar lavage fluid), elevated lung inflammation scores in mice. Curcumin dose-dependently reversed the alterations induced by OVA in the asthmatic mice. Curcumin activated Wnt/β-catenin signaling pathway in DCs and asthmatic mouse lungs.. Curcumin could influence the morphology and function of DCs, ease asthma symptom and inflammatory reaction through the activation of Wnt/β-catenin signaling. These results provide new evidence new evidence for application of curcumin on asthma.

Topics: Animals; Anti-Inflammatory Agents; Asthma; B7-2 Antigen; beta Catenin; Biomarkers; Bronchoalveolar Lavage Fluid; CD11c Antigen; CD40 Antigens; Curcumin; Cytokines; Dendritic Cells; Dexamethasone; Disease Models, Animal; Eosinophils; Female; Inflammation Mediators; Mice; Mice, Inbred C57BL; Pneumonia; Signal Transduction; Wnt Proteins

Pulmonary fibrosis is associated with irreversible, or partially reversible, airflow obstruction and ultimately unresponsiveness to asthma therapies such as corticosteroids. Intranasal curcumin, an anti-inflammatory molecule, has been found effective in allergic asthma. To study the effect of intranasal curcumin on airway remodeling and fibrosis in murine model of chronic asthma, BALB/c mice were sensitized to ovalbumin (OVA) and exposed to OVA aerosol (2%) from day 21 (after sensitization) for 5 weeks (twice/week). Curcumin (intranasal) was administered during the OVA aerosol challenge. Mice exposed to OVA developed inflammation dominated by eosinophils which lead to fibrosis and airway remodeling. Intranasal administration of curcumin significantly inhibited airway inflammation and pulmonary fibrosis, where MMP-9 activities were decreased along with α-smooth muscle actin (α-SMA), MMP-9, TIMP-1, and eotaxin expressions. These results suggest that intranasal curcumin regulates airway inflammation and remodeling in chronic asthma.

Topics: Actins; Administration, Intranasal; Airway Remodeling; Animals; Asthma; Chronic Disease; Curcumin; Eosinophils; Inflammation; Matrix Metalloproteinase 9; Mice; Ovalbumin; Pulmonary Fibrosis; Tissue Inhibitor of Metalloproteinase-1

Asthma, a multifactorial, chronic inflammatory disease encompasses multiple complex pathways releasing number of mediators by activated mast cells, eosinophils and T lymphocytes, leading to its severity. Presently available medications are associated with certain limitations, and hence, it is imperative to search for anti-inflammatory drug preferably targeting signaling cascades involved in inflammation thereby suppressing inflammatory mediators without any side effect. Curcumin, an anti-inflammatory molecule with potent anti-asthmatic potential has been found to suppress asthmatic features by inhibiting airway inflammation and bronchoconstriction if administered through nasal route. The present study provides new insight towards anti-asthmatic potential of intranasal curcumin at lower doses (2.5 and 5.0 mg/kg) in Balb/c mice sensitized and challenged with ovalbumin (OVA) which is effective in inhibiting airway inflammation. These investigations suggest that intranasal curcumin (2.5 and 5.0 mg/kg) regulates airway inflammation and airway obstruction mainly by modulating cytokine levels (IL-4, 5, IFN-ƴ and TNF-α) and sPLA2 activity thereby inhibiting PGD2 release and COX-2 expression. Further, the suppression of p38 MAPK, ERK 42/44 and JNK54/56 activation elucidate the mechanism behind the inhibitory role of intranasal curcumin in asthma progression. Thus, curcumin could be better alternative for the development of nasal formulations and inhalers in near future.

Topics: Administration, Intranasal; Airway Obstruction; Animals; Asthma; Curcumin; Cytokines; Disease Models, Animal; Enzyme Activation; Extracellular Signal-Regulated MAP Kinases; Humans; MAP Kinase Kinase 4; Mice; Mice, Inbred BALB C; p38 Mitogen-Activated Protein Kinases; Prostaglandin D2

Previous studies have shown that curcumin alleviates asthma in vivo. However, the relationship between curcumin and the nuclear factor-E2-related factor 2 (Nrf2)/haem oxygenase (HO)-1 pathway in asthma treatment remains unknown. The aim of the present study was to investigate the mechanisms of curcumin involved in the amelioration of airway inflammation in a mouse asthma model. Curcumin was administrated to asthmatic mice, and bronchoalveolar lavage fluid was collected. Inflammatory cell infiltration was measured by Giemsa staining. Immunoglobulin E production in bronchoalveolar lavage fluid was measured by enzyme-linked immunosorbent assay. Histological analyses were evaluated with haematoxylin-eosin and periodic acid-Schiff staining. Airway hyperresponsiveness was examined by whole-body plethysmography. Nuclear factor-E2-related factor 2, HO-1, nuclear factor-κB and inhibitory κB/p-inhibitory κB levels in lung tissues were detected by western blot, and Nrf2 activity was measured by electrophoretic mobility shift assay. Tumour necrosis factor-α, interleukin (IL)-1β, and IL-6 levels in the small interfering RNA-transfected cells were detected by enzyme-linked immunosorbent assay. Curcumin treatment significantly reduced immunoglobulin E production, attenuated inflammatory cell accumulation and goblet cell hyperplasia, and ameliorated mucus secretion and airway hyperresponsiveness. Nuclear factor-E2-related factor 2 and HO-1 levels in lung tissues were significantly increased. Meanwhile, Nrf2 activity was enhanced. Nuclear factor-κB and p-inhibitory κB levels were elevated in the lung tissue of ovalbumin-challenged mice. Both were restored to normal levels after curcumin treatment. Haem oxygenase-1 and nuclear Nrf2 levels were enhanced in dose- and time-dependent manners in curcumin-treated RAW264.7 cells. Curcumin blocked lipopolysaccharide-upregulated expression of tumour necrosis factor-α, IL-1β, and IL-6. After the cells were transfected with HO-1 or Nrf2 small interfering RNA, lipopolysaccharide-induced pro-inflammation cytokine expression was significantly restored. In summary, curcumin might alleviate airway inflammation in asthma through the Nrf2/HO-1 pathway, potentially making it an effective drug in asthma treatment.

Topics: Animals; Asthma; Curcumin; Cytokines; Female; Gene Knockdown Techniques; Goblet Cells; Heme Oxygenase-1; Hyperplasia; Lipopolysaccharides; Lung; Mice; NF-E2-Related Factor 2; Ovalbumin; RAW 264.7 Cells; RNA, Small Interfering; Signal Transduction

Lipopolysaccharide (LPS) is ubiquitous in the environment and can therefore, exacerbate allergic responses. Studies have suggested immunoregulatory effects of LPS according to route, dose and stage of exposure. Present study has examined whether dose and stage of LPS exposure (during sensitization and challenge with OVA) exacerbates airway inflammations, antigen specific-IgE level, histamine release, Th1/Th2 cytokine response. Further, anti-asthmatic potential of curcumin, through intranasal route has been evaluated for the first time in LPS induced airway inflammation in an ovalbumin (OVA)-challenged mouse asthma model.. Balb/c mice were first sensitized with OVA on 1st and 8th day and exposed to two LPS doses (0.1/1.0 μg) separately on 2nd day and then further exposed to LPS with OVA-aerosol (from 9 to 14 day). Further, lower LPS dose (0.1 μg) was chosen for OVA exposed mouse model of asthma exacerbation study. Intranasal curcumin was administered from 9th to 14th day before every LPS exposure.. Exposure to LPS (0.1 μg) exacerbates airway inflammations in terms of IgE level, Th2-cytokine response (IL-4 and IL-5), histamine release, EPO and MPO activities and oxidative stress. Intranasal curcumin has effectively ameliorated airway exacerbations whereas dexamethasone, a known glucocorticosteroid, was not promising as compared to intranasal curcumin.. Schedule and dose of LPS exposure determines asthma exacerbations and intranasal curcumin could be better immunomodulatory agent in LPS exposed asthma exacerbations.

Topics: Administration, Intranasal; Animals; Asthma; Curcumin; Cytokines; Histamine; Hypersensitivity; Immunoglobulin E; Lipopolysaccharides; Mice; Mice, Inbred BALB C; Ovalbumin; Oxidative Stress

The intestinal absorption and antiasthmatic efficacy of poorly water-soluble curcumin (CUR), which has low solubility and permeability, was increased by fabricating solid dispersion granules (SDGs). The SDG containing CUR (SDG-CUR) was prepared by dispersing CUR in excess Cremophor RH40 as a solubilizer and Ryoto sugar ester L-1695 as an absorption enhancer using fluid bed granulation. We evaluated the physicochemical properties such as crystallinity and dissolution, pharmacokinetics, and antiasthmatic efficacy of SDG-CUR. Our results showed that CUR was molecularly dispersed, and the dissolution of SDG-CUR was significantly higher than that of native CUR. In addition, the blood concentration of SDG-CUR in rats was much higher than that of native CUR. Compared to CUR, SDG-CUR showed a 9.1- and 13.1-fold increase in area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax), respectively. Further, SDG-CUR effectively alleviated airway hyperresponsiveness and levels of T-helper 2 cytokines (interleukin-4, interleukin-5, and interleukin-13) in a murine model of asthma. In conclusion, our results suggest that the SDGs could be considered as a potential oral formulation to enhance the absorption and efficacy of CUR.

Topics: Animals; Asthma; Biological Availability; Caco-2 Cells; Chemistry, Physical; Curcumin; Disease Models, Animal; Female; Humans; Immunoglobulin E; Interleukin-13; Interleukin-4; Interleukin-5; Male; Mice; Mice, Inbred BALB C; Oils; Permeability; Rats; Rats, Sprague-Dawley; Solubility; Surface-Active Agents; Time Factors; X-Ray Diffraction

Dry emulsion containing curcumin (DE-CUR) was prepared for oral delivery of poorly water-soluble curcumin, and its oral bioavailability and antiasthmatic efficacy was evaluated. After comparison of the solubility of curcumin in various oils, Plurol® Oleique CC497 was selected to be the oil phase due to its higher solubility of CUR than other oils. A dry emulsion prepared by spray-drying of a homogenized oil-in-water emulsion was well-reconstituted in water, fabricating similar particle distribution and in vitro release to that of a dispersed homogeneous emulsion before spraying. The release of DE-CUR was much higher than that of curcumin (85.3 vs. 1.7% release at 60 min). Consequently, DE-CUR resulted in 12.0- and 7.1-fold higher Cmax and AUC0-24h than curcumin. In a murine asthma model, DE-CUR effectively suppressed airway hyperresponsiveness and levels of T-helper cytokines such as interleukin-4, inteleukin-5, and interleukin-13. These findings demonstrate that the DE-CUR shows a potential for the development of functional foods or medicines including CUR.

Topics: Administration, Oral; Animals; Anti-Asthmatic Agents; Area Under Curve; Asthma; Biological Availability; Chromatography, High Pressure Liquid; Curcumin; Cytokines; Emulsions; Female; Immunoglobulin E; Interleukin-13; Interleukin-4; Interleukin-5; Male; Mice; Mice, Inbred BALB C; Microscopy, Electron, Scanning; Models, Statistical; Particle Size; Pharmaceutical Preparations; Rats; Rats, Sprague-Dawley; Solubility; Water

Curcumin, a natural product derived from the plant Curcuma longa, has been found to have anti-inflammatory, antineoplastic and antifibrosis effects. It has been reported that curcumin attenuates allergic airway inflammation in mice through inhibiting NF-κB and its downstream transcription factor GATA3. It also has been proved the antineoplastic effect of curcumin through down-regulating Notch1 receptor and its downstream nuclear transcription factor NF-κB levels. In this study, we aimed to investigate the anti-inflammatory effect of curcumin on acute allergic asthma and its underlying mechanisms. 36 male BALB/c mice were randomly divided into four groups (normal, asthma, asthma+budesonide and asthma+curcumin groups). BALF (bronchoalveolar lavage fluid) and lung tissues were analyzed for airway inflammation and the expression of Notch1, Notch2, Notch3, Notch4 and the downstream transcription factor GATA3. Our findings showed that the levels of Notch1 and Notch2 receptors were up-regulated in asthma group, accompanied by the increased expression of GATA3. But the expression of Notch2 receptor was lower than Notch1 receptor. Curcumin pretreatment improved the airway inflammatory cells infiltration and reversed the increasing levels of Notch1/2 receptors and GATA3. Notch3 receptor was not expressed in all of the four groups. Notch4 receptor protein and mRNA expression level in the four groups had no significant differences. The results of the present study suggested that Notch1 and Notch2 receptor, major Notch1 receptor, played an important role in the development of allergic airway inflammation and the inhibition of Notch1-GATA3 signaling pathway by curcumin can prevent the development and deterioration of the allergic airway inflammation. This may be a possible therapeutic option of allergic asthma.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Curcuma; Curcumin; GATA3 Transcription Factor; Inflammation; Male; Mice; Mice, Inbred BALB C; Random Allocation; Receptor, Notch1; Signal Transduction

Curcumin, phytochemical present in turmeric, rhizome of Curcuma longa, a known anti-inflammatory molecule with variety of pharmacological activities is found effective in murine model of chronic asthma characterized by structural alterations and airway remodeling. Here, we have investigated the effects of intranasal curcumin in chronic asthma where animals were exposed to allergen for longer time. In the present study Balb/c mice were sensitized by an intraperitoneal injection of ovalbumin (OVA) and subsequently challenged with 2% OVA in aerosol twice a week for five consecutive weeks. Intranasal curcumin (5mg/kg) was administered from days 21 to 55, an hour before every nebulization and inflammatory cells recruitment, levels of IgE, EPO, IL-4 and IL-5 were found suppressed in bronchoalveolar lavage fluid (BALF). Intranasal curcumin administration prevented accumulation of inflammatory cells to the airways, structural alterations and remodeling associated with chronic asthma like peribronchial and airway smooth muscle thickening, sloughing off of the epithelial lining and mucus secretion in ovalbumin induced murine model of chronic asthma.

Topics: Administration, Intranasal; Animals; Antibody Formation; Asthma; Chronic Disease; Curcuma; Curcumin; Disease Models, Animal; Humans; Immunoglobulin E; Interleukin-4; Interleukin-5; Lung; Mice; Mice, Inbred BALB C; Myocytes, Smooth Muscle; Ovalbumin

The present study aimed to determine the protective effects and the underlying mechanisms of curcumin on ovalbumin (OVA)-induced allergic inflammation in a mouse model of allergic asthma. Asthma mice model was established by ovalbumin. A total of 60 mice were randomly assigned to six experimental groups: control, model, dexamethasone (2 mg/kg), and curcumin (50 mg/kg, 100 mg/kg, 200 mg/kg). Airway resistance (Raw) was measured by the forced oscillation technique, differential cell count in BAL fluid (BALF) was measured by Wright-Giemsa staining, histological assessment was measured by hematoxylin and eosin (HE) staining, BALF levels of Treg/Th17 cytokines were measured by enzyme-linked immunosorbent assay, Treg cells and Th17 cells were evaluated by flow cytometry (FCM). Our study demonstrated that curcumin inhibited OVA-induced increases in eosinophil count; interleukin (IL)-17A level were recovered in bronchoalveolar lavage fluid increased IL-10 level in bronchoalveolar lavage fluid. Histological studies demonstrated that curcumin substantially inhibited OVA-induced eosinophilia in lung tissue. Flow cytometry (FCM) studies demonstrated that curcumin remarkably inhibited Th17 cells and significantly increased Treg cells. The results in vivo show ovalbumin-induced significantly broke Treg/Th17 balance; curcumin treatments markedly attenuated the inflammatory in asthma model by regulating Treg/Th17 balance. Our findings support the possible use of curcumin as a therapeutic drug for patients with allergic asthma.

Topics: Airway Resistance; Animals; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; CD4 Antigens; Curcuma; Curcumin; Eosinophilia; Eosinophils; Female; Inflammation; Interleukin-10; Interleukin-17; Interleukin-2 Receptor alpha Subunit; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Phytotherapy; Plant Extracts; T-Lymphocytes, Regulatory; Th17 Cells

The inhibition of the proliferation of airway smooth muscle cells (ASMCs) is crucial for the prevention and treatment of asthma. Recent studies have revealed some important functions of curcumin; however, its effects on the proliferation of ASMCs in asthma remain unknown. Therefore, in this study, we performed in vitro and in vivo experiments to investigate the effects of curcumin on the proliferation of ASMCs in asthma. The thickness of the airway wall, the airway smooth muscle layer, the number of ASMCs and the expression of extracellular signal-regulated kinase (ERK) were significantly reduced in the curcumin-treated group as compared with the model group. Curcumin inhibited the cell proliferation induced by platelet-derived growth factor (PDGF) and decreased the PDGF-induced phosphorylation of ERK1/2 in the rat ASMCs. Moreover, the disruption of caveolae using methyl-β-cyclodextrin (MβCD) attenuated the anti-proliferative effects of curcumin in the ASMCs, which suggests that caveolin is involved in this process. Curcumin upregulated the mRNA and protein expression of caveolin-1. The data presented in this study demonstrate that the proliferation of ASMCs is inhibited by curcumin in vitro and in vivo; curcumin exerts these effects by upregulating the expression of caveolin-1 and blocking the activation of the ERK pathway.

Topics: Airway Remodeling; Animals; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Bronchi; Caveolin 1; Cell Proliferation; Curcumin; Extracellular Signal-Regulated MAP Kinases; Female; Gene Expression Regulation; Lung; Mice; Myocytes, Smooth Muscle; Ovalbumin; Platelet-Derived Growth Factor; Primary Cell Culture; Protein Transport; Respiratory Hypersensitivity

Curcumin, a phytochemical present in turmeric, rhizome of Curcuma longa, has been shown to have a wide variety of pharmacological activities including anti-inflammatory, anti-allergic and anti-asthmatic properties. Curcumin is known for its low systemic bioavailability and rapid metabolization through oral route and has limited its applications. Over the recent decades, the interest in intranasal delivery as a non-invasive route for drugs has increased as target tissue for drug delivery since nasal mucosa offers numerous benefits. In this study, we evaluated intranasal curcumin following its absorption through nasal mucosa by a sensitive and validated high-performance liquid chromatography (HPLC) method for the determination of intranasal curcumin in mouse blood plasma and lung tissue. Intranasal curcumin has been detected in plasma after 15 min to 3 h at pharmacological dose (5 mg/kg, i.n.), which has shown anti-asthmatic potential by inhibiting bronchoconstriction and inflammatory cell recruitment to the lungs. At considerably lower doses has proved better than standard drug disodium cromoglycate (DSCG 50 mg/kg, i.p.) by affecting inflammatory cell infiltration and histamine release in mouse model of asthma. HPLC detection revealed that curcumin absorption in lungs has started after 30 min following intranasal administration and retained till 3h then declines. Present investigations suggest that intranasal curcumin (5.0 mg/kg, i.n.) has effectively being absorbed and detected in plasma and lungs both and suppressed airway inflammations at lower doses than the earlier doses used for detection (100-200 mg/kg, i.p.) for pharmacological studies (10-20 mg/kg, i.p.) in mouse model of asthma. Present study may prove the possibility of curcumin as complementary medication in the development of nasal drops to prevent airway inflammations and bronchoconstrictions in asthma without any side effect.

Topics: Administration, Intranasal; Animals; Anti-Asthmatic Agents; Asthma; Bronchoalveolar Lavage Fluid; Cell Count; Curcumin; Disease Models, Animal; Eosinophil Peroxidase; Histamine; Lung; Mice; Mice, Inbred BALB C; Ovalbumin

To advance the control of airway epithelial cell function and asthma, we investigated the effects of a new curcumin derivative, CNB001, which possesses improved pharmacological properties. Normal human bronchial epithelial (NHBE) cells were stimulated with synthetic double-stranded RNA, Poly(I:C). CNB001 significantly suppressed IL-6, TNF-α, and GM-CSF production by NHBE cells, and did so more effectively than did curcumin or dexamethasone (DEX). CNB001 significantly inhibited the decrease of E-cadherin mRNA expression and increase of vimentin mRNA expression observed in NHBE cells induced by a combination of TGF-β1 and TNF-α, which are markers of airway remodeling. In NHBE cells stimulated by TGF-β1, CNB001 significantly downregulated the level of active serine peptidase inhibitor clade E member (SERPINE) 1, which is also reported to be related to airway remodeling. Whereas DEX alone significantly increased the active SERPINE1 level, the combination of DEX and CNB001 significantly suppressed active SERPINE1. In addition, CNB001 significantly suppressed neutrophil infiltration, IL-6, TNF-α, IL-13 and active SERPINE1 production in bronchoalveolar lavage fluid of the murine asthma model, which was not observed in the case of DEX. In conclusion, the curcumin derivative, CNB001, is a promising candidate to treat asthma associated with neutrophilic airway inflammation and remodeling.

Topics: Airway Remodeling; Animals; Asthma; Bronchi; Cadherins; Curcumin; Cytokines; Dexamethasone; Female; Glucocorticoids; Humans; Mice; Mice, Inbred BALB C; Plasminogen Activator Inhibitor 1; Pyrazoles; RNA, Double-Stranded

Curcumin has shown considerable pharmacological activity, including anti-inflammatory, but its poor bioavailability and rapid metabolization have limited its application. The purpose of the present study was to formulate curcumin-solid lipid nanoparticles (curcumin-SLNs) to improve its therapeutic efficacy in an ovalbumin (OVA)-induced allergic rat model of asthma. A solvent injection method was used to prepare the curcumin-SLNs. Physiochemical properties of curcumin-SLNs were characterized, and release experiments were performed in vitro. The pharmacokinetics in tissue distribution was studied in mice, and the therapeutic effect of the formulation was evaluated in the model. The prepared formulation showed an average size of 190 nm with a zeta potential value of -20.7 mV and 75% drug entrapment efficiency. X-ray diffraction analysis revealed the amorphous nature of the encapsulated curcumin. The release profile of curcumin-SLNs was an initial burst followed by sustained release. The curcumin concentrations in plasma suspension were significantly higher than those obtained with curcumin alone. Following administration of the curcumin-SLNs, all the tissue concentrations of curcumin increased, especially in lung and liver. In the animal model of asthma, curcumin-SLNs effectively suppressed airway hyperresponsiveness and inflammatory cell infiltration and also significantly inhibited the expression of T-helper-2-type cytokines, such as interleukin-4 and interleukin-13, in bronchoalveolar lavage fluid compared to the asthma group and curcumin-treated group. These observations implied that curcumin-SLNs could be a promising candidate for asthma therapy.

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Curcumin; Disease Models, Animal; Drug Carriers; Histocytochemistry; Interleukin-13; Interleukin-4; Lipids; Lung; Male; Mice; Mice, Inbred BALB C; Nanoparticles; Ovalbumin; Particle Size; Rats; Rats, Sprague-Dawley; Tissue Distribution

Curcumin, a polyphenol compound from Curcuma longa L. has been used for centuries as an anti-inflammatory remedy including asthma. Curcumin has been reported to exert an anti-inflammatory effect, in part, through inhibition of the NF-κB pathway.. The purposes of this study were to determine whether curcumin inhibits NF-κB-dependent transcription in vitro, and test whether treatment with curcumin reduces allergen-induced airway inflammation and hyper-responsiveness in a mouse model of asthma through inhibition of NF-κB pathway.. The effect of curcumin on NF-κB transcriptional activity was investigated using a cell-based luciferase reporter assay in A549 cells and by measuring inhibitory κBα (IκBα), p65, and p50 levels after exposure of Raw264.7 cells to lipopolysaccharide (LPS). BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injection, and challenged with repeated exposure to aerosolized OVA. The effects of daily administered curcumin (200mg/kg body weight, i.p.) on airway hyper-responsiveness (AHR), inflammatory cell number, and IgE levels in bronchoalveolar lavage (BAL) fluid were analyzed. NF-κB activation in lung tissue was also assessed by Western blot analyses.. Curcumin inhibited NF-κB-dependent transcription in reporter assays in A549 cells with an IC(50) of 21.50±1.25μM. Curcumin stabilized IκBα and inhibited nuclear translocation of p65 and p50 in LPS-activated Raw264.7 cells, and curcumin-treated mice showed reduced nuclear translocation of p65 in lung tissue. Treatment with curcumin significantly attenuated AHR and reduced the numbers of total leukocytes and eosinophils in BAL fluid. Infiltration of inflammatory cells and mucus occlusions in lung tissue were significantly ameliorated by treatment with curcumin, which also markedly decreased the level of IgE in BAL fluid.. Curcumin attenuates the development of allergic airway inflammation and hyper-responsiveness, possibly through inhibition of NF-κB activation in the asthmatic lung tissue. Our results indicate that curcumin may attenuate development of asthma by inhibition of NF-κB activation.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Biological Transport; Bronchoalveolar Lavage Fluid; Cell Line; Curcuma; Curcumin; Eosinophils; Female; I-kappa B Proteins; Immunoglobulin E; Inflammation; Inhibitory Concentration 50; Leukocytes; Lung; Mice; Mice, Inbred BALB C; Mucus; NF-kappa B; NF-KappaB Inhibitor alpha; Phytotherapy; Plant Extracts; Rhizome; Transcription Factor RelA

Oropharyngeal candidiasis (OPC) is one of the most common local side effects of current therapy in chronic asthma. New therapeutic options with fewer side effects and reverse chronic changes are needed. Curcumin, as a promising antiinflammatory and antifungal agent, could be a candidate of alternative therapy in asthma. This study aimed to determine the efficacy of orally administrated curcumin on lung histopathology, serum nitric oxide levels and fungal burden in a murine model of asthma and OPC.. Thirty five BALB/c mice were divided into five groups: I, II, III, IV (placebo) and V (control). All groups except the control were sensitized and challenged with ovalbumin. OPC model was established after the model of chronic asthma. Lung histology, serum nitric oxide levels and fungal burden were evaluated after 5 days of treatment with curcumin, dexamethasone, curcumin-dexamethasone combination and placebo. Evaluation of lung histology included subepithelial smooth muscle and epithelial thickness and number of goblet and mast cells by using light microscopy.. All histological parameters improved in curcumin group similar to dexamethasone group. Curcumin and dexamethasone-curcumin combination were also as effective as dexamethasone on decreasing nitric oxide levels. Oral fungal burden was significantly lower in curcumin-treated group than dexamethasone.. In our study we demonstrated that curcumin administration alleviates the pathological changes in asthma and decreases the fungal burden. Curcumin may have a potential effect on treating chronic asthma and decreasing the frequency of the OPC.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Candidiasis, Oral; Colony Count, Microbial; Curcumin; Dexamethasone; Disease Models, Animal; Drug Combinations; Drug Evaluation, Preclinical; Lung; Male; Mice; Mice, Inbred BALB C; Nitric Oxide; Ovalbumin; Tongue

This study was designed to compare the inhibitory effects of thymoquinone (TQ) and curcumin (CMN) on the biological changes associating asthma. TQ appeared to exhibit greater inhibitory effects on the aggregation of inflammatory cells in bronchoalveolar lavage (BAL) fluid and in lung tissues. We also measured the effects of the two agents on serum IgE and the changes in the mRNA levels of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α) and transforming growth factor-β1 (TGF-β1). Serum IgE was significantly decreased by TQ and CMN with TQ being more potent. Also, TQ showed superior inhibitory effects on iNOS and TGF-β1. Meanwhile, CMN was more potent in inhibiting mRNA expression of TNF-α. These results suggest that TQ is more potent in inhibiting the inflammatory changes associating asthma. On the other hand, CMN was a less potent inhibitor of all measured parameters, despite its superior inhibitory effect on TNF-α mRNA levels.

Topics: Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Benzoquinones; Bronchoalveolar Lavage Fluid; Curcumin; Immunoglobulin E; Lung; Male; Mice; Nitric Oxide Synthase Type II; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha

To assess the efficacy of a combination of Boswellia serrata, licorice root (Glycyrrhiza glabra) and Tumeric root (Curcuma longa) as natural leukotriene inhibitor, antiinflammatory and antioxidant products respectively in controlling bronchial asthma.. The study comprised 63 patients with bronchial asthma that are further subdivided into two groups .Group 1 receiving oral capsule (combined herb) in a soft-gelatin capsule 3 times daily for 4weeks and group 2 receiving placebo. Plasma leukotriene C(4) (LTC(4))(,) nitric oxide (NO) and malondialdehyde (MDA) levels were measured and pulmonary function was also assessed in all patients enrolled in the study.. There was a statistically significant decrease in the plasma levels of LTC(4), (MDA), and NO in target therapy group when compared with placebo group.. The used extract contained Boswellia serrata, Curcuma longa and Glycyrrhiza has a pronounced effect in the management of bronchial asthma.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Asthma; Biological Products; Complementary Therapies; Curcuma; Drugs, Chinese Herbal; Glycyrrhiza; Humans; Inflammation Mediators; Leukotriene Antagonists; Leukotriene C4; Malondialdehyde; Middle Aged; Nitric Oxide; Plant Extracts; Plant Roots; Pulmonary Disease, Chronic Obstructive; Young Adult

Curcumin has been strongly implicated as an anti-inflammatory agent, but the precise mechanisms of its action are largely unknown. In this study, we show that curcumin contributes to anti-inflammatory activity in the murine asthma model and lung epithelial cell A549 through suppression of nitric oxide (NO). To address this problem, curcumin was injected into the peritoneum of ovalbumin (OVA)-sensitized mice before the last allergen challenge. OVA challenge resulted in activation of the production of inducible nitric oxide (iNOS) in lung tissue, inflammatory cytokines, recruitment of eosinophils to lung airways, and airway hyper-responsiveness to inhaled methacholine. These effects of ovalbumin challenge were all inhibited by pretreatment of mice with curcumin. Furthermore, supplementation with curcumin in the A549 human airway epithelial cells decreased iNOS and NO production induced by IFN-gamma. These findings show that curcumin may be useful as an adjuvant therapy for airway inflammation through suppression of iNOS and NO.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Bronchoalveolar Lavage Fluid; Cell Line; Curcumin; Disease Models, Animal; Female; Immunoglobulin E; Interleukin-4; Interleukin-5; Lung; Mice; Nitric Oxide; Nitric Oxide Synthase Type II; Ovalbumin; Pneumonia; Respiratory Mucosa

House dust mite (HDM) is a common allergen of allergic asthma. Eosinophils are principal effector cells of allergic inflammation and their adhesion onto human bronchial epithelial cells is mediated by a CD18-intracellular adhesion molecule-1 (ICAM-1)-dependent interaction. We studied the effects of HDM Dermatophagoides pteronyssinus (Der p) 1 on the activation of eosinophils and bronchial epithelial BEAS-2B cells. Cytokines and adhesion molecules were measured using flow cytometry. Transcription factor nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) and signaling molecule p38 mitogen-activated protein kinase (MAPK) were analyzed using electromobility shift assay and western blot, respectively. Der p 1 protein was found to potently induce the release of IL-1beta, IL-6, IL-10, tumor necrosis factor (TNF)-alpha and granulocyte macrophage colony-stimulating factor from eosinophils. Such induction was further up-regulated for IL-6 and IL-10, and down-regulated for TNF-alpha and IL-1beta in eosinophil-BEAS-2B cells co-culture. Surface expression of CD18 and ICAM-1 on eosinophils was greatly increased by Der p 1; such inductive effect on ICAM-1 was also found to be more prominent on BEAS-2B cells from the co-culture than BEAS-2B cells alone. Der p 1 was found to activate NF-kappaB and AP-1 activity in eosinophils alone and in co-culture and BEAS-2B cells in co-culture. Moreover, Der p 1 could activate p38 MAPK in BEAS-2B cells and eosinophils alone and in co-culture. Selective inhibition of NF-kappaB, AP-1 and p38 MAPK resulted in differential suppression of the Der p 1-induced cytokine release and adhesion molecule expression. As an allergen, HDM could therefore induce the release of inflammatory cytokines and expression of adhesion molecules from the interaction of human eosinophils and bronchial epithelial cells.

Topics: Antigens, Dermatophagoides; Arthropod Proteins; Asthma; Bronchi; Cell Adhesion Molecules; Coculture Techniques; Curcumin; Cysteine Endopeptidases; Cytokines; Dermatophagoides pteronyssinus; Enzyme Activation; Eosinophils; Epithelial Cells; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Imidazoles; NF-kappa B; Nitriles; p38 Mitogen-Activated Protein Kinases; Pyridines; Pyroglyphidae; Sulfones; Th2 Cells; Transcription Factor AP-1

Curcuma caesia (family Zingiberaceae) is widely used in India as both an anti-inflammatory and anti-asthmatic in Ayurvedic medicine. However, there are no published pharmacological data on Curcuma caesia on its potential anti-asthmatic activity. Hence, the objective of the present investigation is to study the mechanisms by which the hydroalcoholic extract of Curcuma caesia relaxes the smooth muscle in the bronchioles and vasculature of the respiratory tract.. The hydroalcoholic extract of Curcuma caesia (CC extract) was tested for its per se relaxant effect in guinea pig trachea and also in the presence of various receptor antagonists and enzyme inhibitors namely propranalol, 2', 5'-dideoxyadenosine, methylene blue, glibenclamide, N(omega)-nitro-L-arginine (L-NNA) and alpha-chymotrypsin. Furthermore, the possible role of hydroalcoholic extract in calcium channel modulation was investigated in depolarized rabbit aorta.. The CC extract concentration dependently relaxed the carbachol (1 microM)-induced pre-contractions; the IC50 value was found to be 239.36 microg/ml and the incubation of either receptor antagonists or enzyme inhibitors did not exhibit any effect on the relaxation. In the isotonic Ca2+-free high-K+ (60 mM) depolarized aorta, CC extract (30 microg/ml) inhibited concentration-response curves of cumulative Ca2+ (0.1-30 mM) and the PD'2 value was found to be 4.11 microg/ml.. The extract showed a dose-dependent, non-specific relaxation of pre-contracted isolated guinea pig trachea. The non-specific relaxant effect of the extract may be due to its ability to modulate calcium activity.

Topics: Analysis of Variance; Animals; Asthma; Bronchodilator Agents; Curcuma; Dose-Response Relationship, Drug; Guinea Pigs; Medicine, Ayurvedic; Muscle Relaxation; Muscle, Smooth; Muscle, Smooth, Vascular; Parasympatholytics; Phytotherapy; Plant Extracts; Rabbits; Trachea

Anti-asthmatic property of curcumin (diferuloylmethane), a natural product from the rhizomes of Curcuma longa, has been tested in a guinea pig model of airway hyperresponsiveness. We sensitized guinea pigs with ovalbumin (OVA) to develop certain characteristic features of asthma: allergen induced airway constriction and airway hyperreactivity to histamine. Guinea pigs were treated with curcumin during sensitization (to examine its preventive effect) or after developing impaired airways features (to examine its therapeutic effect). Status of airway constriction and airway hyperreactivity were determined by measuring specific airway conductance (SGaw) using a non-invasive technique, constant-volume body plethysmography. Curcumin (20 mg/kg body weight) treatment significantly inhibits OVA-induced airway constriction (p<0.0399) and airway hyperreactivity (p<0.0043). The results demonstrate that curcumin is effective in improving the impaired airways features in the OVA-sensitized guinea pigs.

Topics: Allergens; Animals; Asthma; Bronchial Hyperreactivity; Curcumin; Dose-Response Relationship, Drug; Guinea Pigs; Male

Asthma is an inflammatory disease, in which eotaxin, MCP-1 and MCP-3 play a crucial role. These chemokines have been shown to be expressed and produced by IL-1beta-stimulated human airway smooth muscle cells (HASMC) in culture. In the present study we were interested to unravel the IL-1beta-induced signal transduction leading to chemokine production. Using Western blot, we observed an activation of p38 MAPK, JNK kinase and p42/p44 ERK when HASMC were stimulated with IL-1beta. We also observed a significant decrease in the expression and the release of eotaxin, MCP-1 and MCP-3 in the presence of SB203580, an inhibitor of p38 MAPK (71 +/- 6%, P < 0.05, n = 8 and 39 +/- 10% P < 0.01, n = 10 respectively), curcumin, an inhibitor of JNK kinase (83 +/- 4.9% and 88 +/- 3.4% respectively, P < 0.01, n = 4). U0126, an inhibitor of p42/p44 ERK, also produced a significant decrease in chemokine production (46.3 +/- 9%, P < 0.01 n = 10 and 67.8 +/- 12%, P < 0.01, n = 12). Pyrrolydine dithiocarbamate, an inhibitor of NF-kappaB was also able to reduce the eotaxin, MCP-1 and MCP-3 expression and production (50 +/- 13%, P < 0.05, n = 10 and 23 +/- 7%, P < 0.05, n = 12). We conclude that p38 MAPK, JNK kinase, ERK and NF-kappaB are involved in the IL-1beta-induced eotaxin, MCP-1, and MCP-3 expression and release in HASMC.

Topics: Asthma; Blotting, Northern; Butadienes; Cells, Cultured; Chemokine CCL11; Chemokine CCL2; Chemokine CCL7; Chemokines; Chemokines, CC; Curcumin; Cytokines; Enzyme Activation; Enzyme Inhibitors; Humans; Imidazoles; Immunoblotting; Interleukin-1; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase 4; MAP Kinase Signaling System; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase Kinases; Mitogen-Activated Protein Kinases; Monocyte Chemoattractant Proteins; Muscle, Smooth; NF-kappa B; Nitriles; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Pyridines; Pyrrolidines; Stimulation, Chemical; Thiocarbamates

Curcumin, a dietary pigment responsible for the yellow color of curry, has been used for the treatment of inflammatory diseases and exhibits a variety of pharmacological effects such as anti-inflammatory, anti-tumor, anti-oxidant, and anti-viral activity. However, it has not been determined whether the effect of curcumin on the production of cytokine affects eosinophil functions and IgE synthesis. In the present study, we examined the effect of curcumin on the production of interleukin (IL)-2, IL-5, granulocyte macrophage-colony stimulating factor (GM-CSF), and IL-4 by lymphocytes from atopic asthmatics in response to house dust mites (Dermatophagoides farinea: Df) in order to clarify a potential application for allergic diseases. Curcumin inhibited Df-induced lymphocyte proliferation and production of IL-2. Exogenous IL-2 reconstituted the proliferative responsiveness of lymphocytes to Df in the presence of curcumin. Furthermore, curcumin inhibited IL-5, GM-CSF, and IL-4 production in a concentration-dependent manner. These results indicate that curcumin may have a potential effect on controlling allergic diseases through inhibiting the production of cytokines affecting eosinophil function and IgE synthesis.

Topics: Adult; Animals; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Curcumin; Dose-Response Relationship, Drug; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Interleukin-4; Interleukin-5; Lymphocyte Activation; Lymphocytes; Mites