stilbenes and Pneumonia

Obstructive airway diseases including asthma, chronic obstructive pulmonary disease and cystic fibrosis present with dyspnea and variety of other symptoms. Physiologically, they are characterized by maximal expiratory flow limitation and pathologically, by inflammation of the airways and the lung parenchyma. Inflammation plays a major role in the gradual worsening of the lung function resulting in worsening symptoms. For many years, scientists focused their efforts in identifying various pathways involved in the chronic inflammation present in these diseases. Further, studies are underway to identify various molecular targets in these pathways for the purpose of developing novel therapeutic agents. Natural agents have been used for thousands of years in various cultures for the treatment of several medical conditions and have mostly proven to be safe. Recent in vivo and in vitro studies show potential anti-inflammatory role for some of the existing natural agents. This review provides an overview of the literature related to the anti-inflammatory effects of some of the natural agents which have potential value in the treatment of inflammatory lung diseases.

Topics: Ambroxol; Anti-Inflammatory Agents, Non-Steroidal; Curcumin; Cystic Fibrosis; Diet; Expectorants; Humans; Justicia; Lung Diseases, Obstructive; Phytotherapy; Picrorhiza; Pneumonia; Prostaglandins; Resveratrol; Stilbenes; Treatment Outcome; Tylophora

Childhood pneumonia has been considered as a major cause of child morbidity and mortality worldwide. We aimed to investigate the effect of resveratral in synergizing with oral amoxicillin to improve the treatment outcome of oral amoxicillin administration against childhood fast breathing pneumonia. 647 children diagnosed fast breathing pneumonia were recruited and randomized to receive oral amoxicillin plus either resveratrol (AX + RV) or placebo (AX + placebo). The primary outcome was defined as treatment failure up to day 3, while the secondary outcome was defined as treatment failure at day 6 and 12 upon follow up. Incidences of treatment failure up to day 3 was significantly lower in the AX + RV group than the AX + placebo group. From day 6-12, the incidences of treatment failure were increased in both treatment groups. However, treatment failure cases were still much lower in the AX + RV group on both revisits. No serious adverse reaction to treatment drugs were found in either of the two groups. Resveratrol improves efficacy of oral amoxicillin against childhood fast breathing pneumonia, supporting the clincial potential of reseveratrol as a potent adjuvent of oral amoxicillin in the treatment of childhood pneumonia with no adverse effects.

Topics: Administration, Oral; Amoxicillin; Anti-Bacterial Agents; Child, Preschool; China; Double-Blind Method; Female; Humans; Infant; Male; Pneumonia; Respiratory System Agents; Resveratrol; Stilbenes; Treatment Outcome

Mycoplasma pneumoniae (MP) can infect both the upper and lower respiratory tracts. Polydatin (PD), a traditional Chinese medicine, is known to have anti-inflammation and antifibrosis properties. However, the protective effects of PD against MP pneumonia (MPP) remain unclear. So, the aim of this study was to describe the therapeutic effects and underlying mechanisms of PD against MPP. BALB/c mice were assigned to three groups: a normal control group, MP infection group, or PD-treated MP infection group. BEAS-2B cells transfected with or without NACHT domain-, leucine-rich repeat-, and pyd-containing protein 3 (NLRP3) were used to confirm the protective mechanisms of PD. Immunohistochemical analysis, Western blot analysis, enzyme-linked immunosorbent assay, and flow cytometry were used in this study. The results showed that PD treatment suppressed MP-induced lung injury in mice by suppressing the expression of inflammatory factors and inhibiting the development of pulmonary fibrosis. Meanwhile, PD treatment inhibited activation of the NLRP3 inflammasome and nuclear factor κB (NF-κB) pathway. Overexpression of NLRP3 reversed the protective effect of PD against MP-induced injury of BEAS-2B cells. Taken together, these results indicate that PD treatment suppressed the inflammatory response and the development of pulmonary fibrosis by inhibiting the NLRP3 inflammasome and NF-κB pathway after MP infection.

Topics: Animals; Cell Line; Drugs, Chinese Herbal; Epithelial Cells; Glucosides; Humans; Inflammasomes; Lung; Mice, Inbred BALB C; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Pneumonia; Pneumonia, Mycoplasma; Protective Agents; Pulmonary Fibrosis; Signal Transduction; Stilbenes

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

Respiratory syncytial virus (RSV) infection is involved in persistent and recurrent wheezing. There are no effective and safe drugs for the sequelae of persistent wheezing after early bronchiolitis. In this study, we investigated the effect of resveratrol on persistent airway inflammation and airway hyperresponsiveness (AHR) induced by RSV infection. RSV-infected mice were sacrificed at serial time points after infection to collect samples and measure the number of inflammatory cells and levels of interferon-gamma (IFN-γ), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF). Airway inflammation, AHR, and the levels of NGF and BDNF were detected after resveratrol administration. Furthermore, Ab-NGF was used to investigate the role of NGF in RSV-induced prolonged airway inflammation and AHR. We found that RSV RNA remained detectable in the lungs of RSV-infected mice on day 60, accompanying persistent airway inflammation and AHR for 60 days. IFN-γ levels in BALF were increased on day 7 but reduced to normal levels by day 14 post-RSV infection, while NGF and BDNF levels gradually increased from day 14 to 60. Furthermore, after resveratrol treatment, the total number of cells in BALF was reduced; the number of inflammatory cells infiltrating the lungs was also lower. Resveratrol attenuated the airway response to methacholine and significantly decreased NGF levels in BALF without affecting BDNF levels. Moreover, airway inflammation and AHR associated with RSV persistence were attenuated after Ab-NGF administration. In all, resveratrol suppresses persistent airway inflammation and AHR might partially through reducing the levels of NGF after RSV infection.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Brain-Derived Neurotrophic Factor; Bronchoalveolar Lavage Fluid; Female; Interferon-gamma; Lung; Mice; Mice, Inbred BALB C; Nerve Growth Factor; Pneumonia; Respiratory Function Tests; Respiratory Hypersensitivity; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; Resveratrol; RNA, Viral; Stilbenes

Cigarette smoking is considered to be the main etiological factor in Chronic Obstructive Pulmonary Disease (COPD). In this study, we explored the potential of resveratrol, to reinstate the effectiveness of dexamethasone when administered as an adjunct in acute lung inflammation induced by cigarette smoke (CS) and lipopolysaccharide (LPS). CS and LPS instillation produced acute inflammatory response exhibited by increased leukocyte count, particularly neutrophils, total protein, MMP-9 activity, cytokines like TNF-α, IL-8 in bronchoalveolar lavage fluid (BALF) as well as elevated myeloperoxidase activity, and lipid peroxidation in lung. These alterations were not abated by dexamethasone (2.5mg/kg & 10mg/kg) and resveratrol (50mg/kg) alone. Combination of resveratrol (50mg/kg) and dexamethasone (2.5mg/kg) significantly reduced all inflammatory parameters. The protective effect of the combination was abolished when co-administered with sirtinol, a SIRT1 inhibitor. The results indicate that the combination therapy may serve as a potential approach for treating lung inflammatory conditions like COPD.

Topics: Acute Disease; Animals; Anti-Inflammatory Agents; Dexamethasone; Disease Models, Animal; Drug Synergism; Drug Therapy, Combination; Lipopolysaccharides; Male; Pneumonia; Rats, Sprague-Dawley; Resveratrol; Smoke; Stilbenes; Tobacco Products

This study was carried out to investigate the effects of resveratrol on cigarette smoke (CS)-induced lung injury. Experimental mice were administrated with 1 mg/kg or 3 mg/ kg resveratrol orally, 1 h prior to CS exposure (five cigarettes a day for 3 consecutive days). Airway inflammation and gene expression changes were assessed. CS exposure increased the number of pulmonary inflammatory cells, coupled with elevated production of tumor necrosis factor α and interleukin-6 in bronchoalveolar lavage fluids. Resveratrol treatment decreased CS-induced lung inflammation. Resveratrol restored the activities of superoxide dismutase, GSH peroxidase, and catalase in CS-treated mice. CS significantly enhanced the nuclear translocation of nuclear factor κB (NF-κB) and NF-κB DNA binding activity, which was impaired by resveratrol pretreatment. In addition, resveratrol promoted CS-induced heme oxygenase-1 (HO-1) expression and activation. Our results collectively indicate that resveratrol attenuates CS-induced lung oxidative injury, which involves decreased NF-κB activity and the elevated HO-1 expression and activity.

Topics: Animals; Bronchoalveolar Lavage Fluid; Catalase; Female; Gene Expression; Glutathione Peroxidase; Heme Oxygenase-1; Interleukin-6; Lung; Lung Injury; Membrane Proteins; Mice; Mice, Inbred Strains; NF-kappa B; Nicotiana; Pneumonia; Resveratrol; Smoke; Stilbenes; Superoxide Dismutase; Transcription Factor RelA; Tumor Necrosis Factor-alpha

The long-standing debate that polyphenol secondary metabolites from dietary plants are important nutritional components continues due to compelling evidence for their abilities to ameliorate degenerative conditions including, cancer, neurological disorders and cardiovascular disease. The clinical use of polyphenols is not, however, mainstream as issues regarding poor selectivity, dosage, toxicity and delivery methods are unresolved. The paper by Rieder et al. suggests that the lack of selectivity, at least for the stilbene, resveratrol, may not be a major limiting factor. The present commentary is a critique of this significant finding that is focused on deciding how the use of resveratrol as clinical medicine could be advanced, and how this new information integrates with current knowledge of polyphenol physiological effects. This commentary suggests that the multi-target nature of polyphenols may be translated into reliable therapy using the current systems/network pharmacology approach concerned with developing viable therapeutic agents that achieve specific effects through interactions with a wide array of targets.. This article is a commentary on Rieder et al., pp. 1244-1258 of BJP 167:6. To view this paper visit http://dx.doi.org/10.1111/j.1476-5381.2012.02063.x.

Topics: Animals; Anti-Inflammatory Agents; Enterotoxins; Female; Lung Injury; Pneumonia; Stilbenes

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

Inhalation of the superantigen,staphylococcal enterotoxin B (SEB), leads to the activation of the host T and invariant natural killer (iNK) T cells, thereby resulting in acute lung inflammation and respiratory failure but the underlying mechanism(s) of disease remain elusive, with limited treatment options. In this study, we investigated the therapeutic effectiveness of resveratrol, a plant polyphenol, during SEB-induced lung inflammation.. C57BL/6 mice were exposed to SEB (50 µg·per mouse), administered intranasally, and were treated with resveratrol (100 mg·kg(-1)) before or after SEB exposure. Lung injury was studied by measuring vascular permeability, histopathological examination, nature of infiltrating cells, inflammatory cytokine induction in the bronchoalveolar fluid (BALF), apoptosis in SEB-activated T cells and regulation of SIRT1 and NF-κB signalling pathways.. Pretreatment and post-treatment with resveratrol significantly reduced SEB-induced pulmonary vascular permeability, and inflammation. Resveratrol significantly reduced lung infiltrating cells and attenuated the cytokine storm in SEB-exposed mice, which correlated with increased caspase-8-dependent apoptosis in SEB-activated T cells. Resveratrol treatment also markedly up-regulated Cd11b+ and Gr1+ myeloid-derived suppressor cells (MDSCs) that inhibited SEB-mediated T cell activation in vitro. In addition, resveratrol treatment was accompanied by up-regulation of SIRT1 and down-regulation of NF-κB in the inflammatory cells of the lungs.. The current study demonstrates that resveratrol may constitute a novel therapeutic modality to prevent and treat SEB-induced lung inflammation inasmuch because it acts through several pathways to reduce pulmonary inflammation.

Topics: Administration, Intranasal; Animals; Anti-Inflammatory Agents; Apoptosis; Cytokines; Endothelial Cells; Enterotoxins; Female; Lung; Lung Injury; Mice; Mice, Inbred C57BL; Pneumonia; Resveratrol; Sirtuin 1; Spleen; Stilbenes; T-Lymphocytes; Transcription Factor RelA

Although studies have demonstrated that resveratrol administration following adverse circulatory conditions is known to be protective, the mechanism by which resveratrol produces the salutary effects remains unknown. We hypothesized that resveratrol administration in males following trauma-hemorrhage decreases cytokine production and protects against lung injury. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure 40 mmHg for 90 min, then resuscitation). A single dose of resveratrol (30 mg/kg of body weight) or vehicle was administered intravenously during resuscitation. Twenty-four hours thereafter, tissue myeloperoxidase activity (a marker of neutrophil sequestration), cytokine-induced neutrophil chemoattractant (CINC)-1, CINC-3, intercellular adhesion molecule (ICAM)-1, and interleukin (IL)-6 levels in the lung and protein concentrations in bronchoalveolar lavage fluid were measured (n = 6 rats/group). One-way ANOVA and Tukey's test were used for statistical analysis. Trauma-hemorrhage increased lung myeloperoxidase activity, CINC-1, CINC-3, ICAM-1, and IL-6 levels and protein concentrations in bronchoalveolar lavage fluid. These parameters were significantly improved in the resveratrol-treated rats subjected to trauma-hemorrhage. The salutary effects of resveratrol administration on attenuation of lung injury following trauma-hemorrhage are likely due to reduction of pro-inflammatory mediators.

Topics: Animals; Cytokines; Hemorrhage; Intercellular Adhesion Molecule-1; Male; Peroxidase; Pneumonia; Rats; Rats, Sprague-Dawley; Resveratrol; Stilbenes; Wounds and Injuries