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1.
J Environ Pathol Toxicol Oncol ; 38(3): 229-238, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679310

RESUMO

Asthma has affected more than 300 million people worldwide and is considered one of the most debilitating global public health problems based on a recent statistical report from the Global Initiative for Asthma. Inflammation of the airways leads to the various interrelated mechanisms of innate and adaptive immunity acting mutually with the epithelium of the respiratory organ. Fucoxanthin is an orange or brown pigment which is naturally found in various seaweeds. To the best of our knowledge, there are no scientific claims or evidence of the curative effects of fucoxanthin against asthma. Hence, this present research was designed to investigate the curative activity of fucoxanthin against ovalbumin-induced asthma in a mouse model. Fucoxanthin (50 mg/kg) showed significant (P < 0.001) antiasthma activity. It effectively decreased intracellular secretion of reactive oxygen species and increased antioxidant enzyme activity. Fucoxanthin also decreased inflammatory cytokine markers in bronchoalveolar lavage fluid. Because fucoxanthin showed effective antiasthma activity against ovalbumin-induced asthma in experimental animals, further research on this natural antioxidant could lead to development of a novel drug for the treatment of asthma in humans.


Assuntos
Antiasmáticos/farmacologia , Antioxidantes/metabolismo , Asma/tratamento farmacológico , Citocinas/imunologia , Inflamação/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Xantofilas/farmacologia , Animais , Biomarcadores/metabolismo , Líquido da Lavagem Broncoalveolar/química , Citocinas/efeitos dos fármacos , Inflamação/induzido quimicamente , Masculino , Camundongos , Ovalbumina/toxicidade
2.
J Environ Pathol Toxicol Oncol ; 38(3): 239-251, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679311

RESUMO

Fucoxanthin, a potent carotenoid present in various natural sources especially from seaweeds; it exhibits several biological effects like anti-neoplastic, anti-mutagenic, anti-diabetic, anti-obesity and anti-inflammatory actions. Fucoxanthin role in chemoprevention of lung cancer in mouse model induced using benzo(a)pyrene [B(a)P] has been presented here. Oral administration of fucoxanthin with and without B(a)P were studied, the results from our study shows that fucoxanthin significantly decreased tumor progression in mice exposed to B(a)P, the obtained data were correlated with increased antioxidant, apoptosis and decreased tumour marker and anti-apoptotic molecules. With respect to apoptosis, fucoxanthin treated animals shows increased apoptosis compared to tumor induced mice by increased expression of caspase 9 and 3 and decreased expression of anti-apoptotic Bcl2 protein. Finally, histopathological and immuno histochemical analysis also revealed that fucoxanthin shows potent anticancer agent by bringing back the damaged tissue treated with B(a)P and also decreases the expression of PCNA in cancer induced mice. The anticancer effect of fucoxanthin may be attributed by several independent mechanisms which play a important roles in the prevention of cancer development, there is also substantial evidences to show that fucoxanthin acts indirectly by increasing the antioxidant capacity of affected tissue and prepared to cope up with oxidative stress which is proved in our study. Thus from our study it is clearly established that fucoxanthin act as a persuasive anticancer drug against lung cancer.


Assuntos
Anti-Inflamatórios/farmacologia , Apoptose/imunologia , Inflamação/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Transdução de Sinais/imunologia , Xantofilas/farmacologia , Animais , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Benzo(a)pireno/toxicidade , Inflamação/induzido quimicamente , Masculino , Camundongos , Transdução de Sinais/efeitos dos fármacos
3.
J Environ Pathol Toxicol Oncol ; 38(3): 285-295, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31679314

RESUMO

Psoriasis is an autoregulated immune and inflammation-based skin disease affecting approximately 3-4% of the worldwide population. Pinitol, conservatively used in ayurvedic medicine, has been shown to disclose an antiinflammatory effect, hold back the T-helper cells, and postpone cardiovascular diseases. In the present study we aimed to reveal the effect of D-pinitol on imiquimod (IMQ)-induced psoriasis-like skin inflammation in a mouse model via the nuclear factor-κB (NF-κB) pathway genes. In the current study, we found that D-pinitol ameliorated the skin abrasion and abridged epithelial thickness, inflammation numbers, and collagen-occupied regions in IMQ-induced psoriasis-like mice. The same results (epithelial thickness, inflammation numbers, and collagen-occupied regions) we achieved in dorsal skin regions. In addition, D-pinitol modified the lipid profile and antioxidant enzyme levels, which means that the IMQ-induced group showed elevated malondialdehyde when compared to D-pinitol. Downregulated expression of glutathione, superoxide dismutase, and catalase in the IMQ-induced group was incomparable with D-pinitol, control, and standard group. Additionally, inflammatory and NF-kB pathway gene levels in the psoriatic mouse skin, which includes tumor necrosis factor-α, interleukin [IL]-6, IL-17A, IL-23,TRAF3, NIK, IKKα, and RelB, were dramatically increased or decreased by treatment with D-pinitol. Histological and morphometric studies disclose the efficiency of D-pinitol. Finally, we found that D-pinitol reserved the TRAF3, NIK, IKKα, and RelB in the psoriatic skin, signifying that it restrains the commencement of NF-κB signaling pathways. The present results suggest that D-pinitol could prove to have tremendous preventive potential against the treatment and prevention of inflammatory disease.


Assuntos
Anti-Inflamatórios/farmacologia , Imiquimode/imunologia , Inflamação/tratamento farmacológico , Inositol/análogos & derivados , Psoríase/tratamento farmacológico , Animais , Inflamação/induzido quimicamente , Inflamação/imunologia , Inositol/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/imunologia , Psoríase/imunologia
4.
Expert Opin Investig Drugs ; 28(10): 871-889, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31566013

RESUMO

Introduction: Functional dyspepsia (FD), defined as the presence of chronic functional symptoms originating from the gastroduodenal, is one of the most common functional gastrointestinal disorders. FD is subdivided into postprandial distress syndrome (PDS), with meal-related symptoms such as postprandial fullness and early satiation, and epigastric pain syndrome (EPS), with meal-unrelated symptoms such as epigastric pain or burning. Therapeutic options for FD are very limited, probably reflecting the complex pathophysiology which comprises disorders of gastric sensorimotor function as well as low-grade duodenal inflammation.Areas covered: This review summarizes recent and ongoing drug development for FD as identifiedExpert opinion: Proton pump inhibitors (PPIs) are the traditional first-line therapy while potassiumcompetitive acid blockers are being studied. Ongoing drug development focuses on gastric motility with prokinetics (dopamine-2 antagonists and 5-HT4 agonists) and fundus relaxant therapies (acotiamide, azapirones), and on sensitivity with peripherally (guanylate cyclase and cannabinoid agonists) and centrally acting neuromodulators. Drugs under development for gastroparesis may be efficacious in PDS. There are emerging data with pro-and antibiotics and with phytotherapeutic agents. Duodenal low-grade inflammation is a newly emerging target which may respond also to PPIs, histamine and leukotriene receptor blockers.


Assuntos
Dispepsia/tratamento farmacológico , Fármacos Gastrointestinais/farmacologia , Gastroenteropatias/tratamento farmacológico , Dor Abdominal/etiologia , Desenvolvimento de Medicamentos/métodos , Dispepsia/fisiopatologia , Fármacos Gastrointestinais/administração & dosagem , Gastroenteropatias/fisiopatologia , Gastroparesia/tratamento farmacológico , Gastroparesia/fisiopatologia , Humanos , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/farmacologia
5.
Zhongguo Zhong Yao Za Zhi ; 44(14): 2943-2946, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602837

RESUMO

Hugan Tablets is a Chinese patent medicine,it has the function of anti-inflammation and reducing transaminase. Based on questionnaire investigation of doctors and a systematic review of research literature on Hugan Tablets,using international clinical practice guidelines' developing methods,with the best available evidence and fully combining expert experience,and following the principle of " evidence-based,consensus-based and experience-based",Expert consensus statement on Hugan Tablets in clinical practice was developed by more than 30 multidisciplinary experts from the nationwide,aimed at guiding and standardizing the rational use of Hugan Tablets by clinicians and to improve clinical efficacy and safety. The expert consensus adopts internationally recognized recommendation criteria for classification of evidence: GRADE. The formation of expert consensus adopts the nominal group technique. Six main considerations are quality of evidence,curative effect,safety,economical efficiency,patient acceptability and other factors. If there is sufficient evidence,a " recommendation" is formed,using GRADE grid voting rule. If there isn' t sufficient evidence,a " consensus opinion" is formed,using majority counting rule. Focus on the indication,usage and dosage,drug use in special population and safety of Hugan Tablets,two recommendations and eight consensus opinions were put forward. Through expert meetings and correspondence,a nationwide consultation and peer review was conducted. This consensus applies to clinicians in hospitals and grass-roots health services,to provide guidance and reference for the rational use of Hugan Tablets.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Inflamação/tratamento farmacológico , Consenso , Humanos , Medicamentos sem Prescrição , Comprimidos
6.
Zhongguo Zhong Yao Za Zhi ; 44(14): 2966-2971, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602841

RESUMO

To study the effects of saikosaponin b2( SS-b2) on inflammatory factors and energy metabolism against lipopolysaccharide/galactosamine( LPS/Gal N) induced acute liver injury in mice. Mice were randomly divided into normal group( equal amount of normal saline),model group( 100 g·kg~(-1) LPS and 400 mg·kg~(-1) Gal N),low,medium,high dose group of SS-b2( SS-b25,10,20 mg·kg~(-1)·d-1) and positive control group( dexamethasone,10 mg·kg~(-1)). All of the groups except for the normal group were treated with LPS/Gal N though intraperitoneally injection to establish the acute liver injury model. The organ indexes were calculated. The levels of serum transaminases( ALT and AST) and the activities of ATPase( Na+-K+-ATPase,Ca2+-Mg2+-ATPase) in liver were detected. The activity of tumor necrosis factor-α( TNF-α),interleukin-1ß( IL-1ß) and interleukin-6( IL-6) were determined by the enzyme-linked immunosorbent assay( ELISA). The contents of lactate dehydrogenase( LDH) in liver were determined by micro-enzyme method. HE staining was used to observe the histopathological changes of the liver. Histochemical method was used to investigate the protein expression of liver lactate dehydrogenase-A( LDH-A). The protein expressions of Sirt-6 and NF-κB in the liver were detected by Western blot. According to the results,compared with the model group,there were significant changes in organ indexes in the high-dose group of SS-b2( P<0. 05). The level of ALT,AST,TNF-α,IL-1ß,IL-6 and the activities of LDH in serum of mice with liver injury were significantly reduced in the medium and high dose groups of SS-b2( P<0. 01). With the increase of the concentration of SS-b2,the range of hepatic lesions and the damage in mice decreased. The activities of Na+-K+-ATPase and Ca2+-Mg2+-ATPase in liver of mice were significantly enhanced in each dose group( P<0. 01). The expression of NF-κB in liver tissues was significantly down-regulated in the medium and high dose group( P<0. 01). Meanwhile,the expression of Sirt-6 protein in the liver of mice with acute liver injury was significantly increased in each dose group( P<0. 01).In summary,SS-b2 has a significant protective effect on LPS/Gal N-induced acute liver injury in mice,which may be related to the down-regulation of NF-κB protein expression and up-regulation of Sirt-6 protein expression to improve inflammatory injury and energy metabolism.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Metabolismo Energético , Inflamação/tratamento farmacológico , Ácido Oleanólico/análogos & derivados , Saponinas/farmacologia , Animais , Citocinas/metabolismo , Galactosamina , Lipopolissacarídeos , Fígado/efeitos dos fármacos , Camundongos , NF-kappa B/metabolismo , Ácido Oleanólico/farmacologia , Distribuição Aleatória , Sirtuínas/metabolismo
7.
Bratisl Lek Listy ; 120(7): 527-531, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31602989

RESUMO

AIM: Carbon tetrachloride (CCl4) is an organic chemical that produces different tissue­damaging effects when ingested or inhaled. Present study aims to determine whether the application of exogenous melatonin, a neurohormone with numerous biological properties, can prevent disturbances in lung tissue antioxidative capacities and arginine metabolism, tissue inflammation and oxidative damage induced by exposure to CCl4 in rats. METHODS: The effects of melatonin on the changes occurring in rat lung tissue after an acute exposure to CCl4 were studied by monitoring alterations in antioxidant capacities, inflammatory parameters, parameters of arginine metabolism, and lipid and protein oxidative damage. RESULTS: The results indicated that melatonin prevents CCl4-induced lung damage by mitigating tissue antioxidant capacity and preventing nitric oxide production through a shift from nitric oxide synthase to arginase. Also, melatonin partially prevented tissue inflammation and molecules' oxidative modification seen after exposure to CCl4. CONCLUSIONS: The protective activity of melatonin can be attributed to its ability to scavenge both free radicals, as well as to its potential to increase tissue antioxidant capacity. The modulation of inflammatory response through both decrease in tissue inflammatory parameters and influence on arginine-nitric oxide metabolism might be an additional mechanism of action (Tab. 1, Fig. 2, Ref. 33).


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Antioxidantes/metabolismo , Melatonina/uso terapêutico , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Arginina/metabolismo , Tetracloreto de Carbono , Inflamação/tratamento farmacológico , Óxido Nítrico/metabolismo , Estresse Oxidativo , Ratos
8.
Mol Biol (Mosk) ; 53(5): 860-870, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31661484

RESUMO

It is time to celebrate the 125th anniversary of the first successful attempt to develop and use a specific high-titer antitoxic serum for treating diphtheria, a deadly infectious disease. This was followed by major advances in passive immunotherapy 75 years ago (production of pooled human IgG for subcutaneous injection) and 50 years ago (widespread technology for producing immunoglobulin preparations for intravenous administration). More than 200 tons of pooled human IgG are produced per year worldwide. The preparation is used primarily for IgG substitution in patients with primary and secondary immunodeficiencies, as well as for an immunomodulating treatment of a growing number of autoimmune and inflammatory diseases. These preparations contain the pooled IgG antibody repertoire of a large population of healthy plasma donors. This repertoire includes antibodies that neutralize pathogens and their factors of virulence, anti-idiotypic antibodies, and antibodies to other foreign and own proteins, as well as to carbohydrate antigens. Naturally polyspecific antibodies that are present in all healthy individuals play an important role as a first-line defense against bacteria and viruses. After exposure to protein-modifying agents, some IgG molecules can acquire the ability to bind novel structurally unrelated antigens. This phenomenon is referred to as induced polyspecificity. The list of these protein-modifying molecules was shown to include low-pH buffers, free heme, pro-oxidative ferrous ions, reactive oxygen species, etc. Such modified antibody preparations may have a therapeutic potential, since their administration to animals with experimental sepsis or aseptic systemic response syndromes significantly improved survival rates, while the same dose of the native preparation had no effect. We also hypothesize that the aggressive protein-modifying molecules released in sites of inflammation and tissue damage could also modify the antigen-binding behavior of surface immunoglobulin B cell receptors and the structurally related T cell receptors. This "specificity editing" of both types of receptors may play a major role in the body's defense mechanisms.


Assuntos
Imunoglobulina G/imunologia , Imunoglobulina G/uso terapêutico , Preparações Farmacêuticas/administração & dosagem , Animais , História do Século XIX , Humanos , Imunoglobulina G/administração & dosagem , Imunoglobulina G/história , Inflamação/tratamento farmacológico , Inflamação/imunologia , Preparações Farmacêuticas/história , Sepse/tratamento farmacológico , Sepse/imunologia
9.
Isr Med Assoc J ; 21(7): 475-479, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507124

RESUMO

BACKGROUND: Uveitis is an inflammatory disorder of the uveal tract of the eye that can affect both adults and children. Non-infectious uveitis can be an expression of a systemic autoimmune condition, or it can be idiopathic. It is a serious disease, associated with possible severe complications leading to visual impairment and blindness. For this reason, a prompt diagnosis and assessment of an appropriate treatment, with the collaboration of specialists such as ophthalmologists and rheumatologists, are extremely important. Many treatment options may be associated to side effects; therefore, clinicians should follow a stepladder approach starting with the least aggressive treatments to induce remission of inflammation. In this review, we reported the current evidence-based treatments for non-infectious uveitis in pediatric and adult patients with particular attention to the biologic response modifier treatment options. Important multicenter studies have demonstrated the efficacy of adalimumab, both in adults (VISUAL I, VISUAL II, VISUAL III) and in children (SYCAMORE, ADJUVITE), while for other agents data are still scarce.


Assuntos
Adalimumab/administração & dosagem , Fatores Imunológicos/administração & dosagem , Uveíte/tratamento farmacológico , Adulto , Criança , Comportamento Cooperativo , Medicina Baseada em Evidências , Humanos , Inflamação/tratamento farmacológico , Uveíte/diagnóstico , Uveíte/patologia
10.
Chem Biol Interact ; 313: 108824, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31542397

RESUMO

Insect-based bioactive components are emerging as novel sources of drugs, effective against various diseases. Inflammation is considered to be an innate immune response developed by different organisms against foreign pathogens and cellular stress. However, repetitive elevated inflammation is considered to be responsible for development of many other diseases including colitis and arthritis. Due to the limited activities and side effects of non-steroidal anti-inflammatory drugs, researchers are continuously looking for alternative sources of drug molecules to alleviate the inflammatory related complications. Recently, insect-based bioactive components, such as venoms, haemocytes, cecropin A, papiliocin, N-acetyldopamine dimers, cecropin-TY1 peptide, cop A3 peptide, glycosaminoglycan, coprisin peptide, silk fibroin microparticles, and silk fibroin nanoparticles have been found to be active against different inflammatory mechanisms and associated diseases. Cancers, are some of the deadliest diseases, which are mainly treated by chemotherapy, radiation therapy and surgery. However, such treatments, mainly chemotherapy, is associated with enormous side effects. Therefore, as an alternative, less hazardous option, compounds from insects with anti-cancerous activity are being explored. Insect-derived compounds, such as cantharidin, norcantharidin, isocoumarin, plancyols A, plancypyrazine A, pancratistatin, narciclasine, and ungeremine, show potential anti-cancerous activity. In this review, we will be discussing the role of different potential drug molecules of insect origin with special emphasis on anti-inflammation and their association with health disorders and cancer.


Assuntos
Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Inflamação/complicações , Insetos/química , Animais , Artrite/tratamento farmacológico , Artrite/etiologia , Produtos Biológicos/farmacologia , Colite/tratamento farmacológico , Colite/etiologia , Humanos , Inflamação/tratamento farmacológico , Neoplasias/tratamento farmacológico , Neoplasias/etiologia
11.
Adv Exp Med Biol ; 1161: 65-75, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31562622

RESUMO

Inflammation is a fundamentally protective process that guards the host from invading pathogens and is central in the repair and regeneration of damaged tissue. However, when uncontrolled, the overzealous response leads to tissue damage and malaise. Indeed, this process is now appreciated to be at the center of many chronic inflammatory diseases including vascular disease and arthritis. Studies investigating the mechanisms through which acute inflammation is actively turned off allowing tissues to regain function demonstrated that the essential fatty acids, arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are enzymatically converted to bioactive mediators. These autacoids carry distinct structures and biological actions, actively reprogramming the inflammatory reaction to promote its termination by counter-regulating the production of pro-inflammatory mediators and regulate leukocyte trafficking as well as phenotype. Recently we found that n-3 docosapentaenoic acid (DPA), which was until then only regarded as a biosynthetic intermediate in the formation of DHA from EPA, is also converted to structurally distinct bioactive mediators that reprogram the host immune response. In the present review we will discuss the evidence underpinning the biological actions of these novel n-3 DPA-derived autacoids in particular as they pertain to the vascular system.


Assuntos
Vasos Sanguíneos , Inibidores de Hidroximetilglutaril-CoA Redutases , Mediadores da Inflamação , Inflamação , Vasos Sanguíneos/efeitos dos fármacos , Vasos Sanguíneos/fisiologia , Ácidos Docosa-Hexaenoicos/química , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Mediadores da Inflamação/química , Mediadores da Inflamação/metabolismo , Leucócitos/efeitos dos fármacos
12.
Life Sci ; 234: 116747, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31408661

RESUMO

AIMS: The present study was aimed to investigate the neuroprotective effect of HSP70 against neuroinflammation in a rotenone-induced Parkinson's disease model. MATERIALS AND METHODS: In the present study, SH-SY5Y cells were treated with HSP70 (5-20 mg/L) for 72 h. Cell viability, reactive oxygen species (ROS) levels, mitochondrial membrane potential (MMP), levels of oxidative markers, mitochondrial fragmentation, apoptosis, and mRNA and protein expressions of signal transducer and activator of transcription (STAT)-3 and nuclear factor-kappa B (NF-κB) were assessed. KEY FINDINGS: Cells treated with 5, 10, 15, and 20 mg/L of HSP70 exhibited increased, by 61.7%, 70.3%, 84.6%, and 96.7%, respectively, in cell viability. ROS and lipid peroxidation levels decreased following treatment with HSP70, and reductions in glutathione (GSH), catalase, glutathione peroxidase (Gpx), and superoxide dismutase (SOD) levels were reversed following treatment with HSP70. Additionally, MMP levels were reduced by 29.7, 46.4, 79.5, and 125.2 relative units following treatment with 5-20 mg/L of HSP70, respectively. HSP70 treatment also decreased levels of fragmented mitochondria and apoptosis, and mRNA and protein expressions of NF-κB and STAT3 were reduced by >25%. SIGNIFICANCE: Taken together, these findings indicate that supplementation with HSP70s recovered cell viability and MMP and reduced levels of ROS, apoptosis, and mitochondrial fragmentation. Additionally, supplementation with HSP70 significantly reduced the expressions of STAT3 and NF-κB.


Assuntos
Regulação para Baixo/efeitos dos fármacos , Proteínas de Choque Térmico HSP70/farmacologia , Inflamação/tratamento farmacológico , NF-kappa B/genética , Fármacos Neuroprotetores/farmacologia , Doença de Parkinson Secundária/tratamento farmacológico , Fator de Transcrição STAT3/genética , Apoptose/efeitos dos fármacos , Linhagem Celular , Humanos , Inflamação/genética , Doença de Parkinson Secundária/genética , RNA Mensageiro/genética , Rotenona
13.
Life Sci ; 234: 116773, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31422095

RESUMO

AIMS: NLRP3 inflammasome activation is essential for the development and prognosis of diabetic cardiomyopathy (DCM). The anti-aging protein Klotho is suggested to modulate tissue inflammatory responses. The aim of the present study was to examine the protective effects of Klotho on DCM. MAIN METHODS: A streptozotocin-induced diabetes mouse model was established to assess the effects of Klotho in vivo, which was administered for 12 weeks. The characteristics of type 1 DCM were evaluated by general status, echocardiography, and histopathology. The expression of associated factors was determined by RT-qPCR and western blotting. Parallel experiments to determine the molecular mechanism through which Klotho prevents DCM were performed using H9C2 cells exposed to high glucose (35 mM). KEY FINDINGS: Diabetes-induced increases in serum creatine kinase-muscle/brain and lactate dehydrogenase levels, cardiac fibrosis, cardiomyocyte apoptosis, and cardiac dysfunction were ameliorated by Klotho. Additionally, Klotho suppressed TXNIP expression, NLRP3 inflammasome activation, and expression of the inflammatory cytokines tumor necrosis factor ɑ, interleukin-1ß, and interleukin-18 in vivo. In high glucose-cultured cardiomyocytes, Klotho and N-acetylcysteine significantly downregulated intracellular reactive oxygen species generation and TXNIP/NLRP3 inflammasome activation. Pretreatment of H9C2 cells with NLRP3 siRNA or Klotho prevented high glucose-induced inflammation and apoptosis in H9C2 cells. SIGNIFICANCE: Our results demonstrate that the protective effect of Klotho on diabetes-induced cardiac injury is associated with inhibition of the NLRP3 inflammasome pathway, suggesting its therapeutic potential for DCM.


Assuntos
Diabetes Mellitus Experimental/imunologia , Cardiomiopatias Diabéticas/imunologia , Glucuronidase/imunologia , Inflamassomos/imunologia , Inflamação/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Animais , Anti-Inflamatórios/imunologia , Anti-Inflamatórios/uso terapêutico , Cardiotônicos/imunologia , Cardiotônicos/uso terapêutico , Linhagem Celular , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Cardiomiopatias Diabéticas/tratamento farmacológico , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/patologia , Glucuronidase/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/patologia , Masculino , Camundongos Endogâmicos C57BL , Ratos , Espécies Reativas de Oxigênio/imunologia
14.
Anticancer Res ; 39(8): 4475-4478, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366547

RESUMO

Chronic inflammation is involved in the development of cancer, lifestyle-related diseases, and autoimmune diseases. It also influences the severity of these diseases. Macrophages that accumulate in tumor tissues and adipose tissues of obesity have been shown to increase expression of inflammatory cytokines, thereby inducing inflammatory changes in these tissues. The macrophage phenotype is believed to be important in mediating inflammatory changes in tissues. Recently, monocytes/macrophages activated with low-dose lipopolysaccharide (LPS) were demonstrated to suppress increased expression of monocyte chemotactic protein (MCP)-1 and inflammatory cytokines (interleukin (IL)-1 ß, IL-8, and tumor necrosis factor (TNF)-α). By suppressing the increased expression of chemotaxis-related and inflammation-related factors, monocytes/macrophages activated with low-dose LPS are considered to suppress the migration of macrophages into tissues and to regulate inflammatory changes in these tissues, respectively. The effects of macrophages activated with low-dose LPS were different from those of macrophages activated with high-dose LPS. In this review, we discuss the usefulness of monocytes/macrophages activation by low-dose LPS.


Assuntos
Inflamação/tratamento farmacológico , Lipopolissacarídeos/uso terapêutico , Neoplasias/tratamento farmacológico , Obesidade/genética , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Quimiocina CCL2/genética , Relação Dose-Resposta a Droga , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Inflamação/genética , Interleucina-1beta/genética , Interleucina-8/genética , Macrófagos/efeitos dos fármacos , Monócitos/efeitos dos fármacos , Neoplasias/genética , Obesidade/patologia , Fator de Necrose Tumoral alfa/genética
15.
Chem Biodivers ; 16(10): e1900174, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31419039

RESUMO

The advanced glycation end products (AGEs) are the compounds produced by non-enzymatic glycation reaction of proteins and sugars, which can induce the generation of free radicals and the expression of inflammatory factors, thereby playing an important role in vascular dysfunction in diabetes. To investigate the effects of caffeic acid (CA) on glycation formed by glucose and protein, various spectroscopic techniques and molecular docking methods were carried out. Furthermore, the protective effects of CA on human umbilical vein endothelial cells (HUVECs) damaged by AGEs were detected. The results indicated that CA inhibited AGEs formation in vitro, decreased the expression of IL-1ß, IL-18, ICAM-1, VCAM-1, NLRP3, Caspase-1 and CRP (C-reactive protein) and reduced the ROS in HUVECs exposed to AGEs. Our findings suggested that the supplementation with dietary CA could prevent and delay the AGEs-induced vascular dysfunction in diabetes.


Assuntos
Ácidos Cafeicos/farmacologia , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Inflamação/tratamento farmacológico , Ácidos Cafeicos/química , Células Cultivadas , Citocinas/antagonistas & inibidores , Citocinas/genética , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Produtos Finais de Glicação Avançada/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Inflamação/metabolismo , Simulação de Acoplamento Molecular , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Relação Estrutura-Atividade
16.
Life Sci ; 233: 116714, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31376370

RESUMO

Increased levels of particulate matter (PM) air pollutants in East Asia have resulted in detrimental health impacts increasing morbidity and mortality. Epidemiological studies suggest a possible relation between the cutaneous exposure of PM and increased oxidative stress and inflammation which lead to skin lesions. The present study utilizes an integrated cell culture model of keratinocytes and fibroblasts to mimic viable skin layers and investigate the possible effects of PM exposure after penetration through corneocytes. The skin perfection is upheld by homeostatic functionality of epidermal cells and the integrity of connective tissues. Exposure to xenobiotics could alter the skin cell homeostasis aggravating premature skin aging. Stimulation of HaCaT keratinocytes by PM collected from Beijing, China (CPM) increased the intracellular ROS levels triggering a cascade of events aggravating inflammatory responses and connective tissue degradation. In HDF fibroblasts, treatment with preconditioned keratinocyte culture media augmented inflammatory responses, cellular differentiation, and connective tissue degradation. Above events were marked by the increased intracellular ROS, inflammatory mediators, pro-inflammatory cytokines, matrix metalloproteinases (MMP)-1 and -2 levels, collagenase, and elastase activity. Fucosterol treatment of keratinocytes dose-dependently attenuated the detrimental effects both in keratinocytes and fibroblasts restoring the conditions near to physiological levels. Further evaluations could be advanced on developing fucosterol, in forms such as rejuvenating cosmeceuticals which could attenuate detrimental responses of CPM exposure.


Assuntos
Fibroblastos/efeitos dos fármacos , Inflamação/tratamento farmacológico , Queratinócitos/efeitos dos fármacos , Material Particulado/efeitos adversos , Dermatopatias/tratamento farmacológico , Pele/efeitos dos fármacos , Estigmasterol/análogos & derivados , Poluentes Atmosféricos/efeitos adversos , Células Cultivadas , Técnicas de Cocultura , Citocinas/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Queratinócitos/metabolismo , Queratinócitos/patologia , NF-kappa B/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Pele/patologia , Dermatopatias/etiologia , Dermatopatias/metabolismo , Dermatopatias/patologia , Estigmasterol/farmacologia
17.
Exp Parasitol ; 204: 107726, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31299264

RESUMO

The aims of this study were to evaluate if the use of copper oxide wire particles, isolated or in association with closantel, in lambs infected with Haemonchus contortus enhances the anthelmintic efficacy of closantel, as well as to evaluate the effects of treatment in hepatic energy metabolism, inflammatory markers and hematological and biochemical tests. The lambs were randomly divided into five groups (6 animals each), as follows: uninfected animals (Control); animals infected with H. contortus (HC); infected and treated with closantel (HC + CL); infected and treated with copper oxide wire particles (HC + Cu); and infected and treated with closantel plus copper oxide wire particles (HC + CL + Cu). The animals of infected groups were infected orally with H. contortus (5,000 L3 -larvae) and on day 14 post infection (p.i) the treatments were initiated. The egg per gram of feces (EPG), butyrylcholinesterase (BuChE), myeloperoxidase (MPO), adenylate kinase (AK) and pyruvate kinase (PK) activities and hematological and biochemical tests were evaluated. Treatments with copper oxide (isolated and associated) were able to reduce the EPG count on days 28, 35, 42 and 49 p.i when compared to HC group, while closantel was able to reduce EPG only from day 35 p.i. Moreover, treatment with closantel (isolated or associated) was able to prevent the inhibition of hepatic AK and PK activities caused by H. contortus infection, which may contribute to efficient intracellular energetic communication in order to maintain the balance between cellular ATP consumption and production. Butyrylcholinesterase and MPO activities were higher in infected lambs compared to uninfected, while treated groups showed lower enzymatic activity compared to the group HC. The use of all therapeutic protocols was able to reduce the EPG count. Based on these evidences, the use of copper oxide plus closantel may be considered an alternative to treat lambs infected by H. contortus.


Assuntos
Anti-Helmínticos/administração & dosagem , Cobre/administração & dosagem , Hemoncose/veterinária , Inflamação/veterinária , Salicilanilidas/administração & dosagem , Doenças dos Ovinos/tratamento farmacológico , Abomaso/metabolismo , Adenilato Quinase/metabolismo , Administração Oral , Animais , Anti-Helmínticos/farmacologia , Anti-Helmínticos/uso terapêutico , Análise Química do Sangue/veterinária , Butirilcolinesterase/sangue , Cápsulas , Metabolismo Energético/efeitos dos fármacos , Contagem de Eritrócitos/veterinária , Fezes/parasitologia , Hemoncose/complicações , Hemoncose/tratamento farmacológico , Hemoncose/metabolismo , Hematócrito/veterinária , Hemoglobinas/análise , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Masculino , Contagem de Ovos de Parasitas/veterinária , Peroxidase/sangue , Piruvato Quinase/metabolismo , Distribuição Aleatória , Salicilanilidas/farmacologia , Salicilanilidas/uso terapêutico , Ovinos , Doenças dos Ovinos/metabolismo , Doenças dos Ovinos/prevenção & controle
18.
Biomed Khim ; 65(3): 222-226, 2019 Apr.
Artigo em Russo | MEDLINE | ID: mdl-31258145

RESUMO

Along with modern new drugs, many therapeutic schemes also include known effective drugs, particularly, glucocorticoids. One of the most distributed of them is prednisolone that has pronounced anti-inflammatory properties. Its disadvantage is short-term circulation, resulting in a number of side effects. For this reason the development of its more effective and safe formulations is carried out. We have obtained the formulation of prednisolone included in nanoparticles from soy phosphatidylcholine with an average diameter of 20 nm. With oral administration to rats and analysis by HPLC an increase in prednisolone maximal concentration in of plasma and the duration of circulation as compared with free drug administration were shown. The experiment with mice with conconavalin A induced inflammation was also carried out: conconavalin A was injected subplantary in an hour after oral administration of both prednisolone formulations in several doses. The index of the inflammatory reaction (determined by the edema degree) was suppressed more effectively in the case of prednisolone in nanoparticles. Maximal suppression (62.2% as compared with 49.6% for free prednisolone) was observed even at a minimal dose (2.5 mg/kg), at which the free drug did not act at all. The results indicate an increase in the efficiency of prednisolone included in phospholipid nanoparticles, that makes it possible to diminish its administered doses and thereby reduce the risk of side effects.


Assuntos
Anti-Inflamatórios/farmacologia , Portadores de Fármacos/química , Glucocorticoides/farmacologia , Inflamação/tratamento farmacológico , Prednisolona/farmacologia , Administração Oral , Animais , Anti-Inflamatórios/farmacocinética , Glucocorticoides/farmacocinética , Camundongos , Nanopartículas , Fosfolipídeos , Prednisolona/farmacocinética , Ratos
19.
Chem Pharm Bull (Tokyo) ; 67(9): 966-976, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31257308

RESUMO

Honokiol, a biphenolic neolignan isolated from Magnolia officinalis, was reported to have a promising anti-inflammatory activity for the treatment of various diseases. There are many efforts on the synthesis and structure-activity relationship of honokiol derivatives. However, regioselective O-alkylation of honokiol remains a challenge and serves as a tool to provide not only some derivatives but also chemical probes for target identification and mode of action. In this study, we examined the reaction condition for regioselective O-alkylation, in which C2 and C4'-alkylated analogs of honokiol were synthesized and evaluated for inhibitory activity on nitric oxide production and cyclooxygenase-2 expression. Furthermore, we successfully synthesized a potential photoaffinity probe consisting of biotin and benzophenone based on a C4'-alkylated derivative.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Compostos de Bifenilo/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Inflamação/tratamento farmacológico , Lignanas/farmacologia , Alquilação , Animais , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/química , Compostos de Bifenilo/síntese química , Compostos de Bifenilo/química , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/síntese química , Inibidores de Ciclo-Oxigenase 2/química , Humanos , Inflamação/metabolismo , Lignanas/síntese química , Lignanas/química , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Células RAW 264.7 , Estereoisomerismo
20.
Chem Biol Interact ; 310: 108738, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31283913

RESUMO

Ischemic stroke and reperfusion injury are a common and serve medical situation in the elderly population. H2S is a gas neuromodulator which also possesses anti-oxidant and anti-inflammatory properties, and is found to play neuroprotective effect in neurodegenerative diseases. This study investigated the effect of endogenous and exogenous H2S in a mouse model of ischemic stroke. 129P2-Cbstm1Unc/J mice with heterozygous mutants in H2S generating enzyme cystathionine ß-synthase were used to study the effect of endogenous H2S. H2S donor NaHS was used as exogenous H2S. Animals were pretreated with H2S and then subjected to middle cerebral artery occlusion surgery. Behavioral outcome was evaluated by novel object recognition test. Inflammatory cytokines were measured using ELISA. Western blot was used to detect the activation of NF-κB. Aged 129P2-Cbstm1Unc/J mice showed exaggerated inflammation and more severe cognitive impairment after ischemia, while exogenous H2S treatment inhibited inflammation and attenuated behavioral impairment. The anti-inflammatory effect of H2S was mediated by inhibiting NF-κB. Our findings suggest that both endogenous and exogenous H2S are involved in the neuroprotection against ischemia/reperfusion-induced cerebral injury.


Assuntos
Sulfeto de Hidrogênio/uso terapêutico , Precondicionamento Isquêmico/métodos , Fármacos Neuroprotetores/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Comportamento Animal/efeitos dos fármacos , Disfunção Cognitiva/tratamento farmacológico , Citocinas/metabolismo , Sulfeto de Hidrogênio/farmacologia , Infarto da Artéria Cerebral Média/complicações , Inflamação/tratamento farmacológico , Camundongos , NF-kappa B/metabolismo , Traumatismo por Reperfusão/prevenção & controle
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