RESUMO
CONTEXT: Chloranthus serratus (Thunb.) Roem. et Schult. (Chloranthaceae) is an herb widely used as a folk medicine treating inflammatory diseases, although it is toxic. OBJECTIVE: To investigate hepatotoxicity and related mechanisms induced by ethanol extracts of different parts of C. serratus in rats. MATERIALS AND METHODS: Sprague Dawley rats were divided into control (Con), ethanol extract of roots (ER), stems (ES), and leaves (EL) groups, and acute oral toxicity studies were conducted. The rats received doses of 4.14, 3.20, and 1.16 g/kg/d extracts for 14 days, respectively. Liver index, liver function and oxidative stress biomarkers, liver pathology, ultrastructure, TNF-α, ICAM-1, and Nrf2/HO-1 proteins expression levels were determined. RESULTS: The LD50 of ER, ES, and EL were higher than 10.35, 8.05, and 2.90 g/kg/p.o., respectively. The liver indexes in the extract groups increased significantly. EL dramatically increased TP, GLB, AST, ALT, ALP, TBA, MDA, ICAM-1, and TNF-α levels (p < 0.01), and induced the most obvious pathological and ultrastructural changes. ES and EL obviously decreased the T-SOD, GSH, CAT, and CHOL levels. Nrf2 and HO-1 proteins expression was reduced significantly in ES (0.77 ± 0.06, 2.33 ± 0.20) and EL (0.23 ± 0.04, 2.14 ± 0.16) groups, and reduced slightly in ER (1.08 ± 0.10; 3.39 ± 0.21) group. DISCUSSION AND CONCLUSION: ES and EL induce stronger hepatotoxicity than ER through oxidative stress and the Nrf2/HO-1 pathway, and the root is a better medicinal part, which provides a basis for clinical research, safe applications, and reasonable development of C. serratus.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Medicamentos de Ervas Chinesas/toxicidade , Estresse Oxidativo , Animais , Doença Hepática Induzida por Substâncias e Drogas/mortalidade , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/análise , Heme Oxigenase (Desciclizante)/fisiologia , Molécula 1 de Adesão Intercelular/análise , Fígado/patologia , Masculino , Fator 2 Relacionado a NF-E2/fisiologia , Ratos , Ratos Sprague-Dawley , Aumento de Peso/efeitos dos fármacosRESUMO
SCOPE: The objectives are to evaluate the anti-inflammatory and anti-atherosclerotic effects of digested total protein and digested protein fractions from chia seed in macrophages in vitro. METHODS AND RESULTS: Total protein and protein fractions (albumin, globulin, glutelin, and prolamin) are isolated from chia seed and digested using simulated gastrointestinal conditions, resulting in digested total protein (DTP) and digested protein fractions (DPF). DTP and DPF are applied (1.0 mg mL-1 ) in RAW 264.4 macrophages stimulated with LPS (1 µg mL-1 ) for inflammation or ox-LDL (80 µg mL-1 ) for atherosclerosis. In the inflammatory process, DTP and DPF reduce p-NF-κB, iNOS, p-JNK, and AP-1. Digested glutelin reduces the secretion of nitric oxide (65.1%), reactive oxygen species (19.7%), prostaglandins (34.6%), TNF-α (24.1%), MCP-1 (18.9%), IL-6 (39.6%), and IL-10 (68.7%). DTP and DPF reduce the NF-κB translocation to nuclei. DTP and digested glutelin reduce iCAM expression (86.4%, 80.8%), LOX-1 (37.3%, 35.7%), iNOS (67.0%, 42.2%), and NF-κB (57.5%, 71.1%). DTP is effective in reducing secretion of nitric oxide (43.4%), lipid accumulation (41.9%), prostaglandins (41.9%), TNF-α (43.3%), MCP-1 (47.6%), and IL-6 (50.5%). Peptides from chia DTP and DPF are also characterized. CONCLUSION: DTP and digested glutelin from chia seed reduce expression and secretion of markers related to inflammation and atherosclerosis pathways.
Assuntos
Aterosclerose/metabolismo , Biomarcadores/análise , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Salvia , Animais , Dinoprostona/metabolismo , Glutens/química , Glutens/farmacologia , Molécula 1 de Adesão Intercelular/análise , Metabolismo dos Lipídeos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Óxido Nítrico/metabolismo , Proteínas de Plantas/farmacocinética , Células RAW 264.7 , Receptores Depuradores Classe E/análise , Sementes/química , Fator de Transcrição AP-1/metabolismoRESUMO
Anthocyanins, the naturally occurring pigments responsible for most red to blue colours of flowers, fruits and vegetables, have also attracted interest because of their potential health effects. With the aim of contributing to major insights into their structure-activity relationship (SAR), we have evaluated the radical scavenging and biological activities of selected purified anthocyanin samples (PASs) from various anthocyanin-rich plant materials: two fruits (mahaleb cherry and blackcurrant) and two vegetables (black carrot and "Sun Black" tomato), differing in anthocyanin content (ranging from 4.9 to 38.5 mg/g DW) and molecular structure of the predominant anthocyanins. PASs from the abovementioned plant materials have been evaluated for their antioxidant capacity using Trolox Equivalent Antioxidant Capacity (TEAC) and Oxygen Radical Absorbance Capacity (ORAC) assays. In human endothelial cells, we analysed the anti-inflammatory activity of different PASs by measuring their effects on the expression of endothelial adhesion molecules VCAM-1 and ICAM-1. We demonstrated that all the different PASs showed biological activity. They exhibited antioxidant capacity of different magnitude, higher for samples containing non-acylated anthocyanins (typical for fruits) compared to samples containing more complex anthocyanins acylated with cinnamic acid derivatives (typical for vegetables), even though this order was slightly reversed when ORAC assay values were expressed on a molar basis. Concordantly, PASs containing non-acylated anthocyanins reduced the expression of endothelial inflammatory antigens more than samples with aromatic acylated anthocyanins, suggesting the potential beneficial effect of structurally diverse anthocyanins in cardiovascular protection.
Assuntos
Antocianinas/química , Anti-Inflamatórios/química , Daucus carota/química , Sequestradores de Radicais Livres/química , Solanum lycopersicum/química , Antocianinas/isolamento & purificação , Antocianinas/farmacologia , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Cromatografia Líquida de Alta Pressão , Daucus carota/metabolismo , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Ensaio de Imunoadsorção Enzimática , Sequestradores de Radicais Livres/isolamento & purificação , Sequestradores de Radicais Livres/farmacologia , Frutas/química , Frutas/metabolismo , Humanos , Molécula 1 de Adesão Intercelular/análise , Molécula 1 de Adesão Intercelular/metabolismo , Solanum lycopersicum/metabolismo , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/análise , Molécula 1 de Adesão de Célula Vascular/metabolismo , Verduras/química , Verduras/metabolismoRESUMO
BACKGROUND: Biliary cirrhosis (BC) is a chronic cholestatic liver disease, in which hepatic fibrosis is an early symptom. This study aimed to identify the biological function and the therapeutic effect of a Chinese traditional medicine, HuaGanTongLuoFang (HGTLF), in a mouse model of BC. METHODS: The mice (n = 72) were randomly divided into a sham group (n =12) and BC group (n = 60). The animals in the BC group were then randomly divided into five groups (n = 12 in each) and treated with three different doses of HGTLF, ureodeoxycholic acid (UDCA), or normal saline (the model group). Four weeks later, serum and liver tissues were obtained from all the animals for analyses. Hematoxylin and eosin (H&E) staining was used to quantify the hepatic morphology, while real-time PCR and Enzyme-linked immunosorbent assay (ELISA) were used to determine the level of hepatic fibrosis-related genes. RESULTS: Compared with the model group, all three doses of HGTLF improved hepatic function, as well as reducing inflammation and fibrogenesis. The best therapeutic effect was observed in the high-dose HGTLF group. Furthermore, HGTLF contributed to down-regulation of hepatic fibrosis-related genes (platelet-derived growth factor [PDGF], transforming growth factor-ß [TGF-ß], p38, nuclear factor-κB [NF-kB], intercellular adhesion molecular-1 [ICAM-1], and tissue inhibitor of metalloproteinase-1 [TIMP-1]). CONCLUSION: The data suggested that HGTLF effectively improved liver function and the morphology of the liver tissue in a mouse model of BC, possibly via suppression of hepatic fibrosis-related signals.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Cirrose Hepática Biliar/tratamento farmacológico , Animais , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Ensaio de Imunoadsorção Enzimática , Molécula 1 de Adesão Intercelular/análise , Fígado/metabolismo , Fígado/fisiologia , Cirrose Hepática Biliar/metabolismo , Cirrose Hepática Biliar/patologia , Masculino , Camundongos , NF-kappa B/genética , NF-kappa B/metabolismo , Fator de Crescimento Derivado de Plaquetas/genética , Fator de Crescimento Derivado de Plaquetas/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Inibidor Tecidual de Metaloproteinase-1/análise , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Glucosamine is a possible cause of vascular endothelial injury in the initial stages of atherosclerosis, through endoplasmic reticulum (ER) stress resulting in fatty streaks in the vascular wall. Quercetin is an antidiabetic and cardiovascular protective agent that has previously been demonstrated to reduce ER stress in human umbilical vein endothelial cells (HUVECs). The present study aimed to investigate whether quercetin prevents glucosamineinduced apoptosis and inflammation via ER stress pathway in HUVECs. The effect of quercetin on cell viability, apoptosis, and protein expression levels of inflammatory cytokines and ER stress markers was investigated in glucosaminesupplemented HUVECs. Quercetin was demonstrated to protect against glucosamineinduced apoptosis, improved cell viability, and inhibited expression of proinflammatory factors and endothelin1. Quercetin treatment also reduced the expression levels of glucoseregulated protein 78, phosphorylated protein kinaselike ER kinase, phosphorylated cJun Nterminal kinase and C/EBP homologous protein. In conclusion, quercetin may have auxiliary therapeutic potential against glucosamineinduced cell apoptosis and inflammation, which may be partially due to alleviation of ER stress.
Assuntos
Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Glucosamina/toxicidade , Quercetina/farmacologia , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Citocinas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Chaperona BiP do Retículo Endoplasmático , Endotelina-1/análise , Ensaio de Imunoadsorção Enzimática , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação/prevenção & controle , Molécula 1 de Adesão Intercelular/análise , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Molécula 1 de Adesão de Célula Vascular/análiseRESUMO
BACKGROUND: Thrombosis and immune dysfunction are two important complications that result from the administration of parenteral nutrition. Endothelial cells within the vasculature are crucial components necessary for maintenance of normal coagulation and immune function. METHODS: We compared the effects of three commercial lipid emulsions (LEs; Intralipid®, ClinOleic® [or Clinolipid®], and Omegaven®) differing in the levels of omega-6 polyunsaturated fatty acids, omega-3 polyunsaturated fatty acids, omega-9 monounsaturated fatty acids, and saturated fatty acids upon endothelial cell fatty acid composition using Gas chromatography, endothelial cell integrity by assessing measurement of apoptosis and necrosis using flow cytometry, endothelial cell inflammatory activation by assessing the induction of ICAM-1 by lipopolysaccharide [LPS]), and transcription factor activation (phosphorylation of NF-κB) using western blot analysis. RESULTS: Gas chromatographic analysis confirmed cellular uptake of the fatty acids within the LEs; furthermore, these fatty acid changes reflected the composition of the oils and egg phosphatides used in the manufacturing of these emulsions. However, the kinetics of fatty acid uptake and processing differed between LEs. Fish oil LE negatively impacted cell viability by doubling the percentage of apoptotic and necrotic cell populations quantified by flow cytometry using Annexin V/Fluorescein and propidium iodide. The soybean oil LE did not alter cell viability, while the olive oil-predominate emulsion improved cell viability. All LEs were capable of suppressing LPS-induced ICAM-1 expression; however, the fish oil LE was more potent than the other emulsions. Fish oil LE supplementation of cells also suppressed LPS-induced phosphorylation of NF-κB, while the soybean oil and olive predominant LE had no effect upon NF-κB phosphorylation. CONCLUSIONS: Lipid emulsions are readily incorporated and stored in the form of triacylglycerols. Soybean oil-based, olive oil-predominant and fish-oil based LEs differentially affected endothelial cell integrity. Importantly, these three LEs were capable of suppressing endothelial cell inflammatory response despite their fatty acid content.
Assuntos
Endotélio Vascular/efeitos dos fármacos , Emulsões Gordurosas Intravenosas/farmacologia , Inflamação/induzido quimicamente , Apoptose/efeitos dos fármacos , Western Blotting , Células Cultivadas , Endotélio Vascular/química , Endotélio Vascular/citologia , Endotélio Vascular/fisiologia , Emulsões Gordurosas Intravenosas/química , Ácidos Graxos/análise , Ácidos Graxos/farmacologia , Humanos , Molécula 1 de Adesão Intercelular/análise , NF-kappa B/análise , Fosfolipídeos/análise , Triglicerídeos/análiseRESUMO
This study investigated the possible antitumor mechanisms of action of Tanshinone VI, one of the components of Salvia miltiorrhiza Bunge, which is used in traditional Chinese herbal medicine. To this end, the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), were evaluated in-vitroin tumor necrosis factor-alpha (TNF-alpha)-stimulated endothelial cells, with, or without the addition of Tanshinone VI (10, 20, 30, or 40 mM) in the culture medium; the effects of Tanshinone VI on angiogenesis was also evaluated with an epithelial cell tube formation assay and its toxicity was evaluated with a colorimetric (MTT) cell viability assay. The results showed that the up-regulation of ICAM-1 and VCAM-1 induced by TNF-alpha was dose-dependently inhibited by Tanshinone VI, with restoration of control levels at the dose of 40 mM; Tanshinone VI also had a remarkable anti-angiogenesis effect, already at the dose of 10 mM, while none of the doses tested had significant effects on cell viability. These results indicate that the antitumor properties of Tanshinone VI can be ascribed to the inhibition of cell adhesion, due to blockage of the up-regulation of cell adhesion molecules, with the consequent inhibition of metastases formation and/or angiogenesis. The lack of toxic effects at the dosage used makes Tanshinone VI a good candidate for its therapeutic use in humans.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Molécula 1 de Adesão Intercelular/análise , Fenantrenos/farmacologia , Molécula 1 de Adesão de Célula Vascular/análise , Células Cultivadas , Relação Dose-Resposta a Droga , HumanosRESUMO
Mastic (Pistacia lentiscus) of the Anacardiaceae family has exhibited anti-inflammatory and antioxidant properties in patients with Crohn's disease. This study was based on the hypothesis that mastic inhibits intestinal damage in inflammatory bowel disease, regulating inflammation and oxidative stress in intestinal epithelium. Four different dosages of P. lentiscus powder in the form of powder were administered orally to trinitrobenzene sulfonic acid-induced colitic rats. Eighty-four male Wistar rats were randomly assigned to seven groups: A, control; B, colitic; C-F, colitic rats daily supplemented with P. lentiscus powder at (C) 50 mg/kg, (D) 100 mg/kg, (E) 200 mg/kg, and (F) 300 mg/kg of body weight; and G, colitic rats treated daily with cortisone (25 µg/kg of body weight). Colonic damage was assessed microscopically. The cytokines tumor necrosis factor-α, intercellular adhesion molecule-1 (ICAM-1), interleukin (IL)-6, IL-8, and IL-10 and malonaldehyde were measured in colonic specimens. Results were expressed as mean ± SE values. Histological amelioration of colitis (P≤.001) and significant differences in colonic indices occurred after 3 days of treatment. Daily administration of 100 mg of P. lentiscus powder/kg of body weight decreased all inflammatory cytokines (P≤.05), whereas 50 mg of P. lentiscus powder/kg of body weight and cortisone treatment reduced only ICAM-1 (P≤.05 and P≤.01, respectively). Malonaldehyde was significantly suppressed in all treated groups (P≤.01). IL-10 remained unchanged. Cytokines and malonaldehyde remained unaltered after 6 days of treatment. Thus P. lentiscus powder could possibly have a therapeutic role in Crohn's disease, regulating oxidant/antioxidant balance and modulating inflammation.
Assuntos
Anti-Inflamatórios/farmacologia , Colite/tratamento farmacológico , Mucosa Intestinal/efeitos dos fármacos , Pistacia/química , Extratos Vegetais/farmacologia , Resinas Vegetais/farmacologia , Trinitrobenzenos/toxicidade , Animais , Colite/induzido quimicamente , Colite/patologia , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Inflamação/patologia , Molécula 1 de Adesão Intercelular/análise , Molécula 1 de Adesão Intercelular/metabolismo , Interleucina-10/análise , Interleucina-10/metabolismo , Interleucina-6/análise , Interleucina-6/metabolismo , Interleucina-8/análise , Interleucina-8/metabolismo , Mucosa Intestinal/patologia , Masculino , Malondialdeído/análise , Malondialdeído/antagonistas & inibidores , Malondialdeído/metabolismo , Ratos , Ratos Wistar , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Plant polyphenols, i.e. green tea extract (GTE), possess high antioxidative and anti-inflammatory capacity, thus being protective in various models of acute inflammation. However, their anti-inflammatory effect and a feasible mechanism in haemorrhage/resuscitation (H/R)-induced liver injury remain unknown. We investigated the effects of GTE and the role of NF-κB in the pathogenesis of liver injury induced by H/R, and their effects on intercellular adhesion molecule-1 (ICAM-1) expression and neutrophil infiltration. Female Lewis rats were fed a standard chow diet (control, ctrl) or a diet containing 0·1 % polyphenolic GTE for five consecutive days before H/R. Rats were haemorrhaged to a mean arterial pressure of 30 (sem 2) mmHg for 60 min and resuscitated. Control groups (sham_ctrl and sham_GTE) underwent surgical procedures without H/R. At 2 h after resuscitation, tissues were harvested. Serum alanine aminotransferase (ALT) and IL-6 were measured. Hepatic necrosis, ICAM-1 expression and polymorphonuclear leucocyte (PMNL) infiltration were assessed. Hepatic expression of IκBα (phospho) was measured. H/R induced strong liver damage with increased necrosis and serum ALT levels. Compared with both sham groups, inflammatory markers (serum IL-6 and hepatic PMNL infiltration) were elevated after H/R (P < 0·05). Also, H/R increased IκBα phosphorylation. GTE administration markedly (P < 0·05) decreased serum ALT and IL-6 levels, hepatic necrosis as well as PMNL infiltration and the expression of ICAM-1 and phosphorylated IκBα compared with H/R. In conclusion, we observed that NF-κB activation plays an important role in the pathogenesis of liver injury after H/R through the up-regulation of hepatic ICAM-1 expression and subsequent PMNL infiltration. GTE pre-treatment prevents liver damage in this model of acute inflammation through a NF-κB-dependent mechanism.
Assuntos
Anti-Inflamatórios/farmacologia , Camellia sinensis , Catequina/uso terapêutico , Hepatopatias/tratamento farmacológico , Fitoterapia , Traumatismo por Reperfusão/tratamento farmacológico , Alanina Transaminase/sangue , Análise de Variância , Animais , Ensaio de Imunoadsorção Enzimática , Feminino , Hemorragia/complicações , Hemorragia/terapia , Molécula 1 de Adesão Intercelular/análise , Interleucina-6/sangue , Fígado/patologia , Hepatopatias/sangue , Hepatopatias/etiologia , NF-kappa B/análise , Necrose/tratamento farmacológico , Necrose/prevenção & controle , Infiltração de Neutrófilos/efeitos dos fármacos , Extratos Vegetais , Ratos , Ressuscitação/efeitos adversosRESUMO
Exotic mushrooms have been used in ancient Chinese medicine due to their immunomodulatory properties for the treatment and/or prevention of chronic diseases. However, only limited data exist on the health benefits of white button mushrooms (WBM), the most common in the American diet. In the current study, we investigated the effects of WBM and shiitake mushrooms (SM) on collagen-induced arthritis (CIA) using a 2 x 3 factorial design in 8-wk-old female dilute brown non-agouti mice that were fed a control diet (n = 37) or the same diet supplemented with 5% lyophilized WBM or SM (n = 27) for 6 wk. CIA was induced by immunizing mice with 100 µg bovine collagen followed by 50 µg LPS on d 20 post-collagen injection. CIA was assessed by mononuclear cell infiltration, bone erosion, plasma IL-6, TNFα, and intercellular adhesion molecule-1 (sICAM-1) concentrations. Compared with the control diet, WBM and SM tended to reduce the CIA index from 5.11 ± 0.82 to 3.15 ± 0.95 (P = 0.06) (median, 6-9 to 1-2) 31 d post-collagen injection. Whereas 58% of control mice had a CIA index ≥ 7, only 23% of WBM and 29% of SM mice did (P = 0.1). Although both types of mushrooms reduced plasma TNFα (34%, WBM; 64%, SM), only SM increased plasma IL-6 by 1.3-fold (P < 0.05). The CIA index was positively correlated with sICAM1 (r = 0.55; P < 0.05) but negatively correlated with TNFα (r = 0.34; P < 0.05). Whether mushrooms are beneficial for arthritis management remains to be investigated. To our knowledge, this is the first report demonstrating a possible health benefit of WBM in arthritis treatment.
Assuntos
Agaricus , Artrite Experimental/prevenção & controle , Cogumelos Shiitake , Animais , Artrite Experimental/patologia , Peso Corporal , Osso e Ossos/patologia , Feminino , Incidência , Molécula 1 de Adesão Intercelular/análise , Interleucina-6/sangue , Leucócitos Mononucleares/fisiologia , Camundongos , Camundongos Endogâmicos DBA , Análise de Regressão , Fator de Necrose Tumoral alfa/sangueRESUMO
We examined the effects of fluid shear stress on metallothionein (MT) gene and protein expression and intracellular free zinc in mouse aorta and in human umbilical vein endothelial cells (HUVECs). Immunostaining of the endothelial surface of mouse aorta revealed increased expression of MT protein in the lesser curvature of the aorta relative to the descending thoracic aorta. HUVECs were exposed to high steady shear stress (15 dyn/cm(2)), low steady shear stress (1 dyn/cm(2)), or reversing shear stress (mean of 1 dyn/cm(2), 1 Hz) for 24 h. Gene expression of three MT-1 isoforms, MT-2A, and zinc transporter-1 was upregulated by low steady shear stress and reversing shear stress. HUVECs exposed to 15 dyn/cm(2) had increased levels of free zinc compared with cells under other shear stress regimes and static conditions. The increase in free zinc was partially blocked with an inhibitor of nitric oxide synthesis, suggesting a role for shear stress-induced endothelial nitric oxide synthase activity. Cells subjected to reversing shear stress in zinc-supplemented media (50 µM ZnSO(4)) had increased intracellular free zinc, reduced surface intercellular adhesion molecule-1 expression, and reduced monocyte adhesion compared with cells exposed to reversing shear stress in normal media. The sensitivity of intracellular free zinc to differences in shear stress suggests that intracellular zinc levels are important in the regulation of the endothelium and in the progression of vascular disease.
Assuntos
Células Endoteliais/metabolismo , Metalotioneína/biossíntese , Resistência ao Cisalhamento , Estresse Mecânico , Zinco/metabolismo , Animais , Aorta/metabolismo , Células Cultivadas , Humanos , Molécula 1 de Adesão Intercelular/análise , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Metalotioneína/genética , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/metabolismo , Zinco/análiseRESUMO
n-3 PUFA have well-recognised cardio-beneficial effects. In contrast, premature coronary deaths are associated with consumption of high levels of trans-fatty acids (TFA). The present study determined the effects of n-3 PUFA and TFA on sudden cardiac death and vascular inflammation. A rat coronary ligation model was used to study the effect of fatty acids on sudden cardiac death, whereas a mouse femoral artery ligation model was used to study compensatory vascular remodelling. Human aortic endothelial cells (HAEC) were utilised for the in vitro studies to investigate expression of inflammatory molecules. Feeding animals an n-3 PUFA-enriched diet caused a sevenfold increase in plasma n-3 PUFA compared with that of the TFA-fed group, whereas a TFA-enriched diet caused a 2.5-fold increase in plasma TFA compared with the n-3 PUFA group. Animals on a TFA diet had a lower survival rate due to sudden cardiac death and exhibited variable degrees of aortic atherosclerotic lesions. Animals on a TFA diet had diminished hindlimb collateral growth, whereas animals on the n-3 PUFA diet exhibited extensive collateral growth about ligated regions. HAEC treated with TFA (trans-18 : 2) showed significantly increased expression of intracellular adhesion molecule-1 and nitrosylation of cellular proteins than those treated with DHA (n-3 PUFA, 22 : 6). The in vivo study demonstrates that, in contrast to TFA, n-3 PUFA improve animal survival after myocardial infarction, prevent development of atherosclerotic lesions and stimulate compensatory vascular remodelling. The in vitro study demonstrates that TFA induce, while n-3 PUFA prevent, vascular inflammation.
Assuntos
Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos trans/administração & dosagem , Vasculite/etiologia , Vasculite/prevenção & controle , Animais , Aorta , Aterosclerose/induzido quimicamente , Aterosclerose/patologia , Linhagem Celular , Vasos Coronários , Dieta , Modelos Animais de Doenças , Células Endoteliais/química , Células Endoteliais/efeitos dos fármacos , Ácidos Graxos/sangue , Artéria Femoral , Humanos , Molécula 1 de Adesão Intercelular/análise , Ligadura , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Infarto do Miocárdio/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
Adhesion molecules are known to play major roles in the initiation and stabilization of cell-to-cell contacts during the immunological response. Human immunodeficiency virus type 1 (HIV-1) exploits those interactions to facilitate infection and propagation processes. The primary objective of the present study was to investigate the ability of antagonists specific for lymphocyte function-associated antigen 1 (LFA-1) to diminish HIV-1 infection and transmission. We demonstrate here that LFA-1 antagonists can significantly reduce HIV-1 replication in primary human cells and virus propagation by affecting cell-to-cell interactions. Moreover, the inhibition of LFA-1-mediated adhesion events also potentiates the antiviral efficacy of the peptide fusion inhibitor T-20. Altogether, our data suggest that LFA-1 antagonists represent promising antiviral agents. Antiadhesion therapy could be considered a complementary strategy targeting cellular functions essential for HIV-1 spreading and against which the combined therapy currently used displays a limited efficacy.
Assuntos
Fármacos Anti-HIV/farmacologia , Proteína gp41 do Envelope de HIV/farmacologia , Inibidores da Fusão de HIV/farmacologia , HIV-1/efeitos dos fármacos , Antígeno-1 Associado à Função Linfocitária/fisiologia , Fragmentos de Peptídeos/farmacologia , Ácidos Ftálicos/farmacologia , beta-Alanina/análogos & derivados , Linhagem Celular , Células Dendríticas/fisiologia , Sinergismo Farmacológico , Enfuvirtida , Humanos , Molécula 1 de Adesão Intercelular/análise , Lovastatina/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Antígeno-1 Associado à Função Linfocitária/efeitos dos fármacos , Vírion/efeitos dos fármacos , Replicação Viral/efeitos dos fármacos , beta-Alanina/farmacologiaRESUMO
In this study, we examine the effect of extra virgin olive oil phenolic compounds on homocysteine-induced endothelial dysfunction and whether the protective effects are related to their different scavenging activities. Structurally related compounds have been assayed for their ability to reduce homocysteine-induced monocyte adhesion as well as the cell surface expression of intercellular adhesion molecule-1 (ICAM-1) in EA.hy.926 cells. As well-known, among the selected phenolic compounds, hydroxytyrosol, homovanillyl alcohol, and the hydroxycinnamic acid derivatives caffeic and ferulic acid display high scavenging activities, while tyrosol and p-coumaric acid are poorly active. All of the tested compounds, approaching potential in vivo concentrations, significantly reduce homocysteine-induced cell adhesion and ICAM-1 expression. Interestingly, we report the first evidence that monophenols tyrosol and p-coumaric acid are selectively protective only in homocysteine-activated cells, while they are ineffective in reducing ICAM-1 expression induced by TNFalpha. Finally, we report the synergistic effect of o-diphenolic and monophenolic compounds.
Assuntos
Antioxidantes/farmacologia , Adesão Celular/efeitos dos fármacos , Células Endoteliais/fisiologia , Homocisteína/farmacologia , Fenóis/farmacologia , Óleos de Plantas/química , Ácidos Cumáricos/farmacologia , Células Endoteliais/química , Células Endoteliais/efeitos dos fármacos , Homocisteína/antagonistas & inibidores , Humanos , Molécula 1 de Adesão Intercelular/análise , Azeite de Oliva , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Propionatos , Células U937RESUMO
BACKGROUND: Expression of cell adhesion molecules on the endothelium and the attachment of monocytes to endothelium may play a major role in the early atherogenic process. AIM OF THE STUDY: We investigated the effects of carnosic acid on the adhesion of U937 cells to IL-1beta-treated human umbilical vein endothelial cells (HUVECs), as well as on the expression of adhesion molecules. RESULTS: Our data showed that pretreatment with 10 and 20 micromol/l carnosic acid significantly reduced the number of U937 cells adhering to IL-1beta-treated HUVECs. In addition, we found that 20 micromol/l carnosic was more effective than 10 micromol/l carnosic acid at inhibiting expression of cell adhesion molecules (ICAM-1, VCAM-1, and E-selectin), the nuclear translocation of NF-kappaB subunits p65 and p50, and the production of ROS in IL-1beta-stimulated HUVECs. CONCLUSIONS: We conclude that carnosic acid inhibits IL-1beta-induced ICAM-1, VCAM-1 and E-selectin expression in HUVECs through a mechanism that involves NFkappaB. We propose that the reduction in binding of human monocytic cell line U937 to IL-1beta-treated HUVECs is due to the anti-inflammatory properties of carnosic acid.
Assuntos
Abietanos/farmacologia , Moléculas de Adesão Celular/análise , Adesão Celular/efeitos dos fármacos , Células Endoteliais , Interleucina-1beta/farmacologia , Monócitos/fisiologia , Extratos Vegetais/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Selectina E/análise , Humanos , Molécula 1 de Adesão Intercelular/análise , NF-kappa B/metabolismo , Espécies Reativas de Oxigênio/antagonistas & inibidores , Células U937 , Veias Umbilicais/citologia , Molécula 1 de Adesão de Célula Vascular/análiseRESUMO
Antiatherosclerotic effects of ethanolic extracts of Artemisia princeps Pampanini cv. Sajabal (ESJ) were investigated in low-density lipoprotein receptor deficient (LDLR(-/-)) mice. The Western diet-induced high levels of total cholesterol and triglyceride were similar in the ESJ and control groups. However, circulating oxidized LDL was significantly decreased in the ESJ group (p < 0.05). ESJ also markedly decreased aortic expression levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta), and reduced the aortic lesion formation and macrophage accumulation by 36.7% (p < 0.05) and 43% (p < 0.01) in the control group, respectively. Additionally, ESJ inhibited atherogenic properties with cytokine-induced surface expression of cell adhesion molecules, chemokines, and monocyte adhesion to the human umbilical vein endothelial cells (HUVECs), and simultaneously suppressed nuclear factor-kappaB (NF-kappaB) activation. These results suggest that ethanolic extracts of Artemisia princeps Pampanini cv. Sajabal contributes to the antiatherosclerotic and anti-inflammatory activities in LDLR(-/-) mice.
Assuntos
Artemisia/química , Aterosclerose/prevenção & controle , Extratos Vegetais/administração & dosagem , Receptores de LDL/deficiência , Animais , Anti-Inflamatórios/administração & dosagem , Aorta/química , Aorta/patologia , Aterosclerose/patologia , Adesão Celular , Células Cultivadas , Colesterol/sangue , Dieta Aterogênica , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/fisiologia , Humanos , Molécula 1 de Adesão Intercelular/análise , Interleucina-1beta/análise , Lipoproteínas LDL/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/farmacologia , Veias Umbilicais , Molécula 1 de Adesão de Célula Vascular/análiseRESUMO
OBJECTIVE: Allergic rhinitis, a disease that impairs quality of life, is characterized by inflammation due to an allergic reaction. Fexofenadine is a second-generation histamine receptor blocker well known for its potent interaction with this inflammatory process. The main aim of this study was to further clarify the anti-inflammatory effects exerted by fexofenadine in patients with intermittent allergic rhinitis. METHODS: Twenty patients with intermittent allergic rhinitis due to birch and mugwort pollen were enrolled. Fexofenadine was administered once a day at a dose of 120 mg. Clinical improvement was assessed by a symptom score, and nasal airway flows were measured by anterior rhinomanometry at baseline and after 2 weeks of treatment with fexofenadine. Nasal smears were tested for eosinophils and nasal lavage fluid were examined for histamine, cysteinyl leukotrienes, soluble intercellular adhesion molecule-1, eosinophil cationic protein, and albumin by enzyme-linked immunosorbent assay. All the tests were performed during the pollen season. RESULTS: Fexofenadine induced a significant improvement in nasal and ocular symptoms (P < .001), nasal edema and secretion (P < .001), and nasal airway flow (P < .001). The clinical improvement was related to a significant reduction in all inflammatory mediators (P < .01 in all cases). CONCLUSION: This study demonstrates that fexofenadine is able to mediate significant changes in different nasal lavage markers from patients with intermittent allergic rhinitis. The changes observed in the markers analyzed in both nasal secretions and serum are attributable to the anti-inflammatory effects of fexofenadine in vivo.
Assuntos
Anti-Inflamatórios/administração & dosagem , Mediadores da Inflamação/imunologia , Líquido da Lavagem Nasal/imunologia , Rinite Alérgica Sazonal/tratamento farmacológico , Terfenadina/análogos & derivados , Adulto , Idoso , Anti-Inflamatórios/efeitos adversos , Antígenos de Plantas/efeitos adversos , Antígenos de Plantas/imunologia , Artemisia/imunologia , Betula/imunologia , Progressão da Doença , Proteína Catiônica de Eosinófilo/análise , Feminino , Histamina/análise , Humanos , Mediadores da Inflamação/análise , Molécula 1 de Adesão Intercelular/análise , Leucotrieno D4/análise , Masculino , Pessoa de Meia-Idade , Líquido da Lavagem Nasal/química , Pólen/efeitos adversos , Pólen/imunologia , Rinite Alérgica Sazonal/imunologia , Terfenadina/administração & dosagem , Terfenadina/efeitos adversos , Resultado do TratamentoRESUMO
Our previous studies have demonstrated the efficacy of partition-herb moxibustion on ulcerative colitis (UC) rats. However, the mechanism of actions of partition-herb moxibustion is still unclear. Most Chinese acupuncturists believe that partition-herb improves the effect of moxibustion therapy. However, this argument lacks confirming experimental and clinical evidence. So, whether partition-herb does play a role in the mechanism of actions of partition-herb moxibustion was reported in this paper. A total of 123 patients were randomly divided into the partition-herb moxibustion group and the control group (partition-bran moxibustion group). Fourteen patients dropped out of the study. Finally, 109 patients finished the intervention. Sixty-one patients with UC received partition-herb moxibustion and 48 patients with UC received partition-bran moxibustion for 72 treatments, one treatment per day, every 12 treatments with an interval of 3 days. The expressions of interleukin-8 (IL-8) and intercellular adhesion molecule-1 (ICAM-1) in the colonic mucosa tissue in mild patients with UC were assayed by immunohistochemistry and RT-PCR. Histology of the colon also was observed at entry and after 72 treatments. Clinical therapeutic effect in partition-herb moxibustion was significantly better than those in partition-bran moxibustion (P < 0.05). Protein and mRNA expression of IL-8, ICAM-1 in the patients was inhibited by both partition-herb moxibustion and partition-bran moxibustion, of those the inhibition in the partition-herb moxibustion group was more obvious (P < 0.01). Partition-herb moxibustion was shown to significantly improve the histology of the colon, and partition-herb was shown to improve the therapeutic effect of moxibustion on treatment of UC patients.
Assuntos
Colite Ulcerativa/metabolismo , Colite Ulcerativa/terapia , Colo/química , Molécula 1 de Adesão Intercelular/análise , Interleucina-8/análise , Moxibustão , Proteínas/análise , Adolescente , Adulto , Idoso , Colite Ulcerativa/patologia , Colo/patologia , Regulação para Baixo , Feminino , Humanos , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular/genética , Interleucina-8/genética , Mucosa Intestinal/química , Masculino , Pessoa de Meia-Idade , Moxibustão/métodos , RNA Mensageiro/análise , SigmoidoscopiaRESUMO
Currants and Sultanas (Vitis vinifera L.) are dried vine products produced in Greece and used broadly in the Mediterranean diet. We aimed to investigate the gastric cancer preventive activity of methanol extracts obtained from currants from three different origins in Greece (Vostizza, Nemea, and Messinia) as well as methanol extracts obtained from Sultanas cultivated in the island of Crete as to inhibition of cell proliferation, induction of apoptosis, and inhibition of inflammation. All extracts from 500 microg dried raisins studied suppressed cell proliferation, significantly those obtained from Sultanas from Crete and currants from Nemea. Flow cytometric analysis of Annexin-V labeled cells indicated that Cretan Sultana, Nemea, and Messinia currants at 500 microg dried product/ml medium significantly induced cell death. All extracts from 500 microg dried raisins statistically decreased protein and mRNA levels of ICAM-1 in TNF-alpha stimulated cells. Measurement of IL-8 protein levels and quantification for IL-8 mRNA showed no significant decrease. These results indicate that the methanol extracts from currants, rich in phenolic compounds, exhibit cancer preventive efficacy by limiting cell proliferation, inducing cell death, and suppressing ICAM-1 levels in AGS cells.
Assuntos
Anticarcinógenos/farmacologia , Extratos Vegetais/farmacologia , Neoplasias Gástricas/prevenção & controle , Vitis , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Flavonoides/análise , Humanos , Molécula 1 de Adesão Intercelular/análise , Molécula 1 de Adesão Intercelular/genética , Interleucina-8/análise , Interleucina-8/genética , Fenóis/análise , Polifenóis , RNA Mensageiro/análise , Neoplasias Gástricas/patologia , Fator de Necrose Tumoral alfa/farmacologia , Vitis/químicaRESUMO
The role of cell adhesion molecules has been studied extensively in the process of inflammation, and these molecules are critical components of carcinogenesis and cancer metastasis. This study investigated the effect of tanshinone I derived from the traditional herbal medicine, Salvia miltiorrhiza Bunge, on the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-alpha (TNF-alpha)-stimulated endothelial cells. Furthermore, this study investigated the effect of tanshinone I on cancer growth, invasion and angiogenesis on human breast cancer cells MDA-MB-231, both in vitro and in vivo. Tanshinone I dose dependently inhibited ICAM-1 and VCAM-1 expressions in human umbilical vein endothelial cells (HUVECs) that were stimulated with TNF-alpha for 6 h. Pretreatment with tanshinone I significantly reduced adhesion of either monocyte U937 or MDA-MB-231 cells to HUVECs. Interestingly, the inhibitory effect of tanshinone I on monocyte and cancer cell adhesion to HUVECs was mimicked by transfection with ICAM-1 and VCAM-1 small interfering RNA. In addition, tanshinone I effectively inhibited TNF-alpha-induced production of vascular endothelial growth factor (VEGF) and VEGF-mediated tube formation in HUVECs. Tanshinone I also inhibited TNF-alpha-induced VEGF production in MDA-MB-231 cells and migration of MDA-MB-231 cells through extracellular matrix. Additionally, reduction of tumor mass volume and decrease of metastasis incidents by tanshinone I were observed in vivo. In conclusion, this study provides a potential mechanism for the anticancer effect of tanshinone I on breast cancer cells, suggesting that tanshinone I may serve as an effective drug for the treatment of breast cancer.