stilbenes and Asthma

Resveratrol, a natural polyphenolic molecule with several biological activities, is a well recognized anti-oxidant, anti-aging and cancer chemopreventive agent. Moreover, resveratrol anti-inflammatory and antifibrotic properties have been demonstrated both in vitro and in different animal models of inflammatory pathologies, including bowel and liver diseases. We review the evidence of resveratrol protective role in respiratory diseases such as acute lung injury, asthma, chronic obstructive pulmonary disease and lung fibrosis. We conclude that resveratrol and its derivatives may act as a therapeutic agents in respiratory diseases and pertinent clinical trials should be performed.

Topics: Acute Lung Injury; Animals; Anti-Inflammatory Agents; Antioxidants; Asthma; Disease Models, Animal; Fibrosis; Humans; Inflammation; Liver Diseases; Lung; Mice; Pulmonary Disease, Chronic Obstructive; Resveratrol; Stilbenes

The aim of this article is to provide an overview of the classical histone deacetylase (HDAC) enzymes and HDAC inhibitors. The discussion is focused on the potential anti-asthmatic effects of this group of compounds.. Medline was used with the search terms, "asthma and HDAC," "asthma and Trichostatin A," "asthma and valproic acid," "allergic airways disease and HDAC," "allergic airways disease and Trichostatin A," and "allergic airways disease and valproic acid." Manuscripts from the past decade were accessed. Historical literature dating from the 1960s was accessed for the use of anti-epileptics in the treatment of asthma.. Preliminary clinical trials with anti-epileptic drugs including the well-known HDAC inhibitor, valproic acid, have shown long-lasting anti-asthmatic effects providing the basis for the evaluation of this class of compounds in asthma. Studies using the prototypical HDAC inhibitor, Trichostatin A, in well-established murine models of allergic airways disease have also indicated beneficial effects.. Although the precise mechanisms are still controversial, inhibition of airway hyperresponsiveness and agonist-induced contraction as well as anti-inflammatory effects have been described for HDAC inhibitors in asthma.

Topics: Anti-Inflammatory Agents; Asthma; Histone Deacetylase Inhibitors; Histone Deacetylases; Humans; Resveratrol; Stilbenes

Sirtuin1 (Sirt1) is a NAD-dependent class III histone deacetylase (HDAC), and regulates pulmonary immune/inflammatory system and the aging process mainly through post-translational modification. Sirt1 could become a potential target for treatment of lung diseases due to participating in the development of a variety of lung diseases. In this paper, physiological characteristics, biological activities, modification regulations and its relationship with chronic obstructive pulmonary emphysema, asthma and lung cancer are reviewed.

Topics: Animals; Asthma; Benzamides; Humans; Lung Diseases; Lung Neoplasms; Naphthols; Protein Processing, Post-Translational; Pulmonary Disease, Chronic Obstructive; Resveratrol; Sirtuin 1; Stilbenes

The putative cardiovascular risks and benefits of the ingestion of wine and alcohol-containing spirits have been well publicized; however, less attention has been focused upon the health effects of wine and spirits consumption on the respiratory system. This paper will highlight epidemiologic, clinical and experimental data on the effects of wine and distilled spirits [and the chemical components thereof] on lung function, chronic obstructive pulmonary disease progression, lung cancer risk, risk of developing acute respiratory distress syndrome, high altitude pulmonary edema and wine [sulfite] associated asthma. Several studies have demonstrated a positive [beneficial] effect of light-to-moderate wine consumption on pulmonary function, while chronic ingestion of distilled spirits may have either no effect, or a negative effect. Studies in Scandinavia, Europe and South America have suggested a possible protective effect of wine ingestion against lung cancer, especially adenocarcinoma. Resveratrol [3,5,4'-trihydroxystilbene] a polyphenolic compound found in red wine, has anti-oxidant, anti-inflammatory and estrogen agonist effects and may be responsible for some of the health benefits of wine. The spectrum of potentially beneficial clinical effects of resveratrol and other wine-derived compounds is discussed.

Topics: Adenocarcinoma; Alcohol Drinking; Alcoholic Beverages; Alcoholism; Altitude Sickness; Antioxidants; Asthma; Female; Humans; Lung; Lung Neoplasms; Male; Pulmonary Disease, Chronic Obstructive; Pulmonary Edema; Respiratory Distress Syndrome; Resveratrol; Stilbenes; Sulfites; Wine

Topics: Animals; Asthma; Cytokines; Disease Models, Animal; Glucose; Glycolysis; Histones; Humans; Interleukin-4; Leukocytes, Mononuclear; Mice; Pyroglyphidae; Stilbenes; Th2 Cells; TOR Serine-Threonine Kinases

Reactive oxygen species (ROS) and epithelial-mesenchymal transition (EMT) play a critical role in transforming growth factor (TGF)-β1-mediated fibrotic airway remodeling in asthma. Polydatin (PD) is a small natural molecule in Chinese medicine; it is isolated from Polygonum cuspidatum and has antioxidative properties. In this study, we aimed to determine whether PD was protective against ROS-induced pulmonary fibrosis in asthma. Ovalbumin (OVA) was used to induce asthma in a mouse model that was treated with or without PD. We also created nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown BEAS-2B cells and investigated whether PD reversed TGF-β1-induced pulmonary epithelial cell EMT by promotion of Nrf2-mediated antioxidation. Immunofluorescence showed that ROS and TGF-β1 expression was significantly increased in lung tissue from the OVA-induced asthma model. PD treatment inhibited activity of ROS and TGF-β1. Immunohistochemistry showed that PD treatment decreased OVA-induced lung ROS, TGF-β1 expression and fibroblasts. Western blotting showed that PD treatment reversed OVA-induced NADPH oxidase (NOX)1/4 expression by promoting Nrf2-mediated heme oxygenase-1 and NADPH dehydrogenase (quinone)-1 expression. PD treatment suppressed OVA-induced EMT and lung fibroblast protein expression in lung tissue. Nrf2 downregulation suppressed the protective effect of PD by promoting TGF-β1-induced ROS and EMT and accumulation of extracellular-matrix-related protein. All these data indicate that PD has potential therapeutic effects in asthma by promoting Nrf2-mediated antioxidation.

Topics: Airway Remodeling; Animals; Antioxidants; Asthma; Cells, Cultured; Disease Models, Animal; Epithelial Cells; Epithelial-Mesenchymal Transition; Glucosides; Humans; Lung; Male; Mice; Mice, Inbred BALB C; Mice, Nude; NF-E2-Related Factor 2; Ovalbumin; Reactive Oxygen Species; Signal Transduction; Stilbenes; Transforming Growth Factor beta1

Asthma is an inflammatory disease caused by an imbalance of Th1 and Th2 cells. In general, asthma is characterized by a stronger Th2 response. Most conventional asthma treatment focuses on improving airway flow or suppression of airway inflammation. To reduce the side effects of currently used asthma medicines, we have conducted studies on natural products that have no side effects. 2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside (TSG), the main compound of

Topics: Animals; Asthma; Bronchoalveolar Lavage Fluid; Cell Count; Cytokines; Disease Models, Animal; Female; Glucosides; Immunoglobulin Class Switching; Inflammation; Inflammation Mediators; Lung; Mice, Inbred C57BL; Ovalbumin; Protective Agents; Respiratory Hypersensitivity; Stilbenes; Th1 Cells; Th2 Cells

A growing number of studies have demonstrated that the activity and expression level of sirtuin-1 (SIRT1) are decreased in asthma patients; however, the mechanisms underlying decreased SIRT1 expression and function are still not completely understood. Interleukin (IL)-6 plays important roles in inflammation during allergic asthma. In this study, we examined whether loss of SIRT1 activity regulated the expression of IL-6 and further verified the underlying mechanisms.. The human airway epithelial cell line 16HBE was used to test the effects of the SIRT1 inhibitor (salermide) on expression of IL-6. IL-6 mRNA and protein expression were assessed with real-time polymerase chain reaction (PCR), immunochemistry, and ELISA. OVA-challenged mice were used as an asthma model to investigate the effect of SIRT1 activation on IL-6 and relative Akt phosphorylation level.. We found that inhibition of SIRT1 increased IL-6 mRNA and protein levels in a time-dependent manner, which was accompanied by increased Akt pathway activation in 16HBE cells. Furthermore activation of Akt showed upregulated expression of the IL-6 protein whereas Akt inhibitor, LY294002 or Akt siRNA significantly inhibited SIRT1-regulated IL-6 expression. Conversely, activation of SIRT1 inhibited Akt activation and IL-6 expression in an asthmatic mice model and 16HBE cells.. Our results indicate the potential role of SIRT1 in regulating inflammation by modulation of IL-6 expression in an Akt-dependent manner during allergic asthma.

Topics: Animals; Asthma; Blotting, Western; Cell Line; Chromones; Disease Models, Animal; Enzyme Inhibitors; Enzyme-Linked Immunosorbent Assay; Epithelial Cells; Humans; Immunohistochemistry; Interleukin-6; Lung; Morpholines; Naphthols; Phenylpropionates; Proto-Oncogene Proteins c-akt; Resveratrol; RNA, Small Interfering; Signal Transduction; Sirtuin 1; Stilbenes

The dietary modulation of gut microbiota, suggested to be involved in allergy processes, has recently attracted much interest. While several studies have addressed the use of fibres to modify intestinal microbial populations, information about other components, such as phenolic compounds, is scarce. The aim of this work was to identify the dietary components able to influence the microbiota in 23 subjects suffering from rhinitis and allergic asthma, and 22 age- and sex-matched controls. The food intake was recorded by means of an annual food frequency questionnaire. Dietary fibre tables were obtained from Marlett et al., and the Phenol-Explorer database was used to assess the phenolic compound intake. The quantification of microbial groups was performed using an Ion Torrent 16S rRNA gene-based analysis. The results showed a direct association between the intake of red wine, a source of stilbenes, and the relative abundance of Bacteroides, and between the intake of coffee, rich in phenolic acids, and the abundance of Clostridium, Lactococcus and Lactobacillus genera. Despite epidemiological analyses not establishing causality, these results support the association between polyphenol-rich beverages and faecal microbiota in allergic patients.

Topics: Adult; Asthma; Bacterial Load; Bacteroides; Clostridium; Coffee; Diet; Dietary Fiber; Feces; Female; Flavonoids; Gastrointestinal Microbiome; Humans; Hydroxybenzoates; Hypersensitivity; Lactobacillus; Lactococcus; Male; Middle Aged; Phenols; Rhinitis, Allergic; Stilbenes; Wine

Previous in vitro studies have demonstrated that resveratrol is able to significantly inhibit the upregulation of mucin 5AC (MUC5AC), a major component of mucus; thus indicating that resveratrol may have potential in regulating mucus overproduction. However, there have been few studies regarding the resveratrol‑mediated prevention of MUC5AC overproduction in vivo, and the mechanisms by which resveratrol regulates MUC5AC expression have yet to be elucidated. In the present study, an ovalbumin (OVA)‑challenged murine model of asthma was used to assess the effects of resveratrol treatment on mucus production in vivo. The results demonstrated that resveratrol significantly inhibited OVA‑induced airway inflammation and mucus production. In addition, the mRNA and protein expression levels of MUC5AC were increased in the OVA‑challenged mice, whereas treatment with resveratrol significantly inhibited this effect. The expression levels of murine calcium‑activated chloride channel (mCLCA)3, an important key mediator of MUC5AC production, were also reduced following resveratrol treatment. Furthermore, in vitro studies demonstrated that resveratrol significantly inhibited human (h)CLCA1 and MUC5AC expression in a dose‑dependent manner. These results indicated that resveratrol was effective in preventing mucus overproduction and MUC5AC expression in vivo, and its underlying mechanism may be associated with regulation of the mCLCA3/hCLCA1 signaling pathway.

Topics: Animals; Asthma; Cell Line; Disease Models, Animal; Epithelial Cells; Female; Gene Expression Regulation; Humans; Lung; Mice, Inbred BALB C; Mucin 5AC; Mucus; Pneumonia; Resveratrol; Stilbenes

Obesity and insulin resistance have been associated with deterioration in asthma outcomes. High oxidative stress and deficient activation of AMP-activated protein kinase (AMPK) have emerged as important regulators linking insulin resistance and inflammation. This study aimed to evaluate the effects of resveratrol on obesity-associated allergic pulmonary inflammation. Male C57/Bl6 mice fed with high-fat diet to induce obesity (obese group) or standard-chow diet (lean group) were treated or not with resveratrol (100mg/kg/day, two weeks). Mice were sensitized and challenged with ovalbumin (OVA). At 48h thereafter, bronchoalveolar lavage fluid was performed, and lungs collected for morphological studies and Western blot analysis. Treatment of obese mice with resveratrol significantly reduced hyperglycemia and insulin resistance, as well as the body measures (body mass, fat mass, % fat, and body area). OVA-challenge promoted a higher increase in pulmonary eosinophil infiltration in obese compared with lean mice, which was nearly abrogated by resveratrol treatment. Resveratrol markedly increased the phosphorylated AMPK expression in lung tissues of obese compared with lean mice. Resveratrol reduced the p47phox expression and reactive-oxygen species (ROS) production, and elevated the superoxide dismutase (SOD) levels in lung tissues of obese mice. The increased pulmonary levels of TNF-α and inducible nitric oxide synthase (iNOS) in obese mice were also normalized after resveratrol treatment. In lean mice, resveratrol failed to affect the levels of fasting glucose, p47phox, ROS levels, TNF-α, iNOS and phosphorylated AMPK. Resveratrol exhibits protective effects in obesity-associated lung inflammation that is accompanied by local AMPK activation and antioxidant property.

Topics: AMP-Activated Protein Kinases; Animals; Antioxidants; Asthma; Cell Movement; Cells, Cultured; Disease Progression; Eosinophils; Lung; Mice; Mice, Inbred Strains; Obesity; Pneumonia; Resveratrol; Stilbenes

Eosinophils exert a number of inflammatory effects through the degranulation and release of intracellular mediators, and are considered to be key effector cells in allergic disorders, including asthma. In order to investigate the regulatory effects of the natural polyphenol, resveratrol, on eosinophils derived from asthmatic individuals, the cell counting Kit‑8 assay and flow cytometry analysis were used to determine cell proliferation and cell cycle progression in these cells, respectively. Cellular apoptosis was detected using annexin V-fluorescein isothiocyanate/propidium iodide double‑staining. The protein expression levels of p53, p21, cyclin‑dependent kinase 2 (CDK2), cyclin A, cyclin E, Bim, B‑cell lymphoma (Bcl)‑2 and Bcl‑2‑associated X protein (Bax) were measured by western blot analysis following resveratrol treatment. The results indicated that resveratrol effectively suppressed the proliferation of eosinophils from asthmatic patients in a concentration‑ and time‑dependent manner. In addition, resveratrol was observed to arrest cell cycle progression in G1/S phase by increasing the protein expression levels of p53 and p21, and concurrently reducing the protein expression levels of CDK2, cyclin A and cyclin E. Furthermore, resveratrol treatment significantly induced apoptosis in eosinophils, likely through the upregulation of Bim and Bax protein expression levels and the downregulation of Bcl‑2 protein expression. These findings suggested that resveratrol may be a potential agent for the treatment of asthma by decreasing the number of eosinophils.

Topics: Adult; Apoptosis; Asthma; Cell Cycle Checkpoints; Cell Proliferation; Cells, Cultured; Eosinophils; Female; Humans; Male; Resveratrol; Stilbenes; Young Adult

Asthma is an inflammatory disease of the lungs characterized by airway remolding. In this study, we examined whether resveratrol exerts protective effects on allergic asthma in a murine model. To investigate the effects of resveratrol on allergic airway inflammation in house dust mite (HDM)-induced mouse asthma and explore its mechanism, a chronic asthma mouse model was established by intranasally administering extracts of HDM (25μg of protein in 10μl of saline) for 5days/week for up to 7 consecutive weeks. Resveratrol (50mg/kg body weight), dexamethasone (1mg/kg body weight) or a vehicle was administered orally 1h before antigen challenges for up to 2weeks. Compared with the HDM-induced mice, the level of TNF-α of the BALF in the resveratrol+HDM-treated mice had obviously decreased. Histological examination of the lung tissue revealed that the resveratrol treatments attenuated the fibrotic response and airway inflammation. In addition, resveratrol inhibited the expression of the Syk protein and degranulation in mast cells. The presented findings collectively suggest that resveratrol has a therapeutic effect on mouse allergic asthma, and its mechanism of action might be related to reducing the production of the Syk protein.

Topics: Animals; Anti-Inflammatory Agents; Antigens, Dermatophagoides; Asthma; Cell Degranulation; Cell Line; Chronic Disease; Dexamethasone; Disease Models, Animal; Female; Gene Expression Regulation; Humans; Intracellular Signaling Peptides and Proteins; Lung; Mast Cells; Mice; Mice, Inbred BALB C; Protein-Tyrosine Kinases; Pyroglyphidae; Resveratrol; Stilbenes; Syk Kinase; Tumor Necrosis Factor-alpha

Resveratrol, a natural polyphenolic compound known for its antioxidative and antiinflammatory effects, exerts antiasthmatic effects, although the mechanism underlying these effects remains elusive. The phosphatase and tensin homology deleted on chromosome ten gene (PTEN) is involved in the pathogenesis of asthma, and PTEN overexpression in asthmatic mice improved asthma symptoms. To investigate whether the antiasthmatic mechanisms of resveratrol correlated with the upregulation of PTEN expression, an ovalbumin (OVA)-induced murine asthma model was used to determine the effectiveness of resveratrol treatment. PTEN mRNA and protein expression was assessed with real-time polymerase chain reaction (PCR) and immunochemistry. To determine whether airway remodeling occurred, the inner airway wall, mucous layer, and smooth muscle areas were each determined using an image analysis system. The lung epithelial cell line 16HBE was used to study the regulation of PTEN expression levels by resveratrol in vitro. Our data demonstrated that resveratrol inhibited OVA-induced airway inflammation and airway remodeling in asthmatic mice. PTEN expression was decreased in the murine asthma model, although the expression of PTEN was restored following treatment with resveratrol. Correlation efficiency analysis showed that PTEN expression was associated with the degree of airway remodeling. Further in vitro studies demonstrated that the inhibition of Sirtuin 1 (SIRT1) activity by a SIRT1 inhibitor and RNA interference decreased PTEN protein expression, while resveratrol attenuated the decreases in PTEN expression induced by the SIRT1 inhibitor. These data suggest the mechanism of the antiasthmatic effects of resveratrol in an OVA-induced murine asthma model, which resulted in the upregulation of PTEN via SIRT1 activation.

Topics: Airway Remodeling; Animals; Anti-Asthmatic Agents; Asthma; Cell Line; Disease Models, Animal; Female; Humans; Lung; Mice, Inbred BALB C; Ovalbumin; PTEN Phosphohydrolase; Resveratrol; Sirtuin 1; Stilbenes; Up-Regulation

The aim of the study was to investigate the potential anti-inflammatory effects in -experimental allergic asthma of natural polyphenolic compounds or their single major components. The experiment was performed after 21-days sensitization of guinea pigs with ovalbumin suspension. Changes in airway reactivity after the long-term treatment with the polyphenolic compounds Provinol and Flavin-7 and their single major components quercetin and resveratrol during were assessed using a whole body plethysmography. Reactivity of tracheal smooth muscle was studied in vitro in response to cumulative doses of the bronchoconstrictive mediators histamine and acetylcholine. Furthermore, concentrations of the inflammatory cytokines IL-4 and IL-5 were measured in bronchoalveolar lavage fluid. The results demonstrate significant anti-inflammatory effects of Provinol and Flavin-7 exerted in the airways. In contrast, chronic treatment with quercetin and resveratrol, single components of the two polyphenols, did not show such activity. We conclude that polyphenolic compounds are more effective in the anti-inflammatory effects in the airways than their separate components.

Topics: Acetylcholine; Animals; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Bronchoconstriction; Bronchoconstrictor Agents; Guinea Pigs; Histamine; Interleukin-4; Interleukin-5; Lung; Muscle, Smooth; Ovalbumin; Plethysmography, Whole Body; Polyphenols; Quercetin; Respiratory System; Resveratrol; Stilbenes; Trachea

In asthma, reduced histone deacetylase activity and enhanced histone acetyltransferase activity in the lungs have been reported. However, the precise function of Sirtuin 1 (Sirt1), a class III histone deacetylase, and the effect of the Sirt1 activator SRT1720 on allergic inflammation have not been fully elucidated.. The effect of SRT1720, a synthetic activator of Sirt1, in an ovalbumin (OVA)-induced asthma mouse model was investigated. The effect of SRT1720 and resveratrol on OVA stimulation in splenocytes from OVA-sensitized and challenged mice was also examined.. In OVA-sensitized and challenged mice (OVA mice) compared with saline-sensitized and challenged mice (control mice), Sirt1 messenger RNA expression in the lungs was decreased (P = 0.02), while cellular infiltration, airway eosinophilia and bronchoalveolar lavage (BAL) fluid levels of interleukin (IL)-4, IL-5 and IL-13 were increased (P < 0.01). In OVA mice, SRT1720 treatment decreased total and eosinophil cell counts and IL-5 and IL-13 levels in the BAL fluid compared with the vehicle treatment (P < 0.05). In OVA mice, SRT1720 treatment also decreased inflammatory cell lung infiltrates histologically (P = 0.002). Both SRT1720 and resveratrol suppressed OVA-induced cell proliferation and IL-6 (P < 0.05) and tumour necrosis factor-α (TNF-α) (P < 0.05) production in splenocytes (P < 0.01).. The Sirt1 activator SRT1720 suppressed inflammatory cell infiltration and cytokine production in an OVA-induced mouse model of asthma. SRT1720 and resveratrol suppressed OVA-induced splenocyte proliferation and TNF-α and IL-6 production. Sirt1 activators might have beneficial effects in asthmatics by suppressing inflammation.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Cytokines; Disease Models, Animal; Female; Heterocyclic Compounds, 4 or More Rings; Lung; Mice; Mice, Inbred BALB C; Ovalbumin; Pneumonia; Respiratory System; Resveratrol; RNA, Messenger; Sirtuin 1; Stilbenes

Asthma is a chronic airway inflammatory disorder which is characterized by reversible airway obstruction, airway hyperresponsiveness and airway inflammation. Oxidative stress has been shown to be strongly associated with most of the features of asthma and leads to accumulation of phosphatidyl inositol (3,4) bis-phosphate {PtdIns(3,4)P2} which is the major substrate for inositol polyphosphate 4 phosphatase (INPP4A). PtdIns(3,4)P2 in turn activates PI3K pathway and contributes to oxidative stress. Thus, there exists a vicious loop between oxidative stress and lipid phosphatase signaling. In this context, we have recently shown that INPP4A, a crucial molecular checkpoint in controlling PI3K-Akt signaling pathway, is downregulated in allergic airway inflammation. Resveratrol, a potent antioxidant found in red wines, has been shown to attenuate asthma features in murine model of allergic airway inflammation (AAI), however the underlying mode of its action was not completely understood. In this study, the effect of resveratrol on mitochondrial dysfunction, PI3K-Akt signaling and inositol polyphosphate 4 phosphatase was studied in murine model of allergic airway inflammation. We observed that resveratrol treatment of allergic mice was found to significantly downregulate oxidative stress and restore mitochondrial function. It also decreased calpain activity and restored the expression of INPP4A in lungs which in turn reduced Akt kinase activity and Akt phosphorylation. These results suggest a novel mechanism of action of resveratrol in attenuating asthma phenotype by downregulating PI3K-Akt pathway via upregulating INPP4A.

Topics: Animals; Anti-Asthmatic Agents; Asthma; Calpain; Gene Expression Regulation; Male; Mice; Mice, Inbred BALB C; Ovalbumin; Oxidative Stress; Phosphatidylinositol 3-Kinases; Phosphoric Monoester Hydrolases; Phosphorylation; Proto-Oncogene Proteins c-akt; Resveratrol; Stilbenes

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

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

Asthma is an inflammatory disease of the airways, and the current focus in managing asthma is the control of inflammation. Resveratrol (3,4,5-trihydroxystilbene) is a polyphenolic stilbene found in the skins of red fruits, including grapes, that may be responsible for some of the health benefits ascribed to consumption of red wine. We investigated the suppressive effects of resveratrol on asthmatic parameters such as cytokine release, eosinophilia, airway hyperresponsiveness, and mucus hypersecretion, in an OVA-induced allergic mouse model of asthma. Resveratrol significantly inhibited increases in T-helper-2-type cytokines such as IL-4 and IL-5 in plasma and bronchoalveolar lavage fluid (BALF), and also effectively suppressed airway hyperresponsiveness, eosinophilia, and mucus hypersecretion, in the asthmatic mouse model. The efficacy of resveratrol was similar to that of dexamethasone, a glucocorticoid used as a positive control. These results suggest that resveratrol may have applications in the treatment of bronchial asthma.

Topics: Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Asthma; Bronchoalveolar Lavage Fluid; Dexamethasone; Disease Models, Animal; Eosinophilia; Female; Goblet Cells; Immunoglobulin E; Immunoglobulin G; Interleukin-4; Interleukin-5; Lung; Mice; Mice, Inbred BALB C; Mucus; Ovalbumin; Resveratrol; Stilbenes

To explore the anti-inflammatory effects of amurensin H on asthma-like reaction induced by allergen in sensitized mice.. BALB/c mice were sensitized by ovalbumin (OVA, ip) on d 0 and d 14 and challenged with 1% OVA on d 18 to 22. Mice developed airway eosinophilia, mucus hypersecretion, and elevation in cytokine levels. Mice were administered amurensin H orally at the doses of 49, 70, or 100 mg/kg once every day from d 15 to the last day. Bronchoalveolar lavage fluid (BALF) were collected at 24 h and 48 h after the last OVA challenge. Levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 4 (IL-4), interleukin 5 (IL-5), and interleukin 13 (IL-13) in BALF were measured using ELISA method. Differential cell counts of macrophages, lymphocytes, neutrophils and eosinophils were performed in 200 cells per slide (one slide per animal). Lung tissue sections of 6-mum thickness were stained with Mayer's hematoxylin and eosin for assessment of cell infiltration, mucus production, and tissue damage.. Oral administration of amurensin H significantly inhibited OVA-induced increases in total cell counts, eosinophil counts, and TNF- alpha, IL-4, IL-5 and IL-13 levels in BALF. In addition, amuresin H dramatically decreased OVA-induced lung tissue damage and mucus production.. Amurensin H may have therapeutic potential for the treatment of allergic airway inflammation.

Topics: Animals; Anti-Inflammatory Agents; Asthma; Benzofurans; Cytokines; Interleukin-13; Interleukin-4; Interleukin-5; Lung; Male; Mice; Mice, Inbred BALB C; Molecular Structure; Ovalbumin; Plants, Medicinal; Stilbenes; Tumor Necrosis Factor-alpha; Vitis

Topics: Animals; Asthma; Butadienes; Calcium-Calmodulin-Dependent Protein Kinases; Enzyme Inhibitors; Guinea Pigs; Imidazoles; Nitriles; Protein-Tyrosine Kinases; Pyrimidines; Signal Transduction; Stilbenes

Topics: Anti-Allergic Agents; Asthma; Histamine H1 Antagonists; Humans; Stilbenes