iridoids and Pneumonia

Airway inflammation has been implicated in evoking progressive pulmonary disorders including chronic obstructive pulmonary disease (COPD) and asthma as a result of exposure to inhaled irritants, characterized by airway fibrosis, mucus hypersecretion, and loss of alveolar integrity. The current study examined whether oleuropein, a phenylethanoid found in olive leaves, inhibited pulmonary inflammation in experimental models of interleukin (IL)-4-exposed bronchial BEAS-2B epithelial cells and ovalbumin (OVA)- or cigarette smoke (CS)-exposed BALB/c mice. Nontoxic oleuropein at 1-20 μM diminished eotaxin-1-mediated induction of α-smooth muscle actin and mucin 5AC in epithelial cells stimulated by IL-4 at the transcriptional levels. Oral supplementation of 10-20 mg/kg oleuropein reduced the airway influx of eosinophils and lymphocytes as well as IL-4 secretion in lung promoted by OVA inhalation or CS. In addition, oleuropein suppressed infiltration of macrophages and neutrophils through blocking OVA inhalation- and CS-promoted induction of ICAM-1, F4/80, CD68, and CD11b in airways. OVA-exposed pulmonary fibrosis was detected, while alveolar emphysema was evident in CS-exposed mouse lungs. In alveolar epithelial A549 cells exposed to CS extracts, oleuropein attenuated apoptotic cell loss. Collectively, oleuropein inhibited pulmonary inflammation leading to asthmatic fibrosis and alveolar emphysema driven by influx of inflammatory cells in airways exposed OVA or CS. Therefore, oleuropein may be a promising anti-inflammatory agent for treating asthma and COPD.

Topics: Animals; Apoptosis; Asthma; Cigarette Smoking; Emphysema; Humans; Immunoglobulin E; Interleukin-4; Iridoid Glucosides; Iridoids; Male; Mice; Mice, Inbred BALB C; Pneumonia

Staphylococcus aureus (S. aureus) is a major cause of pneumonia that often affects young and immunocompetent patients. Inflammation plays an important role in the development of S. aureus-induced pneumonia. Geniposide, a major iridoid glucoside component of gardenia fruit, has been reported to have anti-inflammatory and anti-oxidative effects. The purpose of this study was to investigate the protective effects of geniposide on S. aureus-induced pneumonia in mice. Lung histopathological changes were detected by hematoxylin-eosin (H&E) staining. Lung myeloperoxidase (MPO) activity, wet-to-dry (W/D) ratio, and inflammatory cytokine levels in bronchoalveolar lavage fluid (BALF) were measured. The results showed that S. aureus-induced lung histopathological changes were attenuated by geniposide. S. aureus-induced MPO activity and lung W/D ratio were inhibited by treatment of geniposide. Furthermore, the levels of TNF-α and IL-1β in the BALF were also suppressed by geniposide. In addition, geniposide significantly inhibited S. aureus-induced nuclear factor kappa B (NF-κB) activation. Taken together, these results showed that geniposide inhibited S. aureus-induced pneumonia in mice by inhibiting NF-κB signaling pathway. Geniposide might be used as a potential agent for the treatment of S. aureus-induced pneumonia.

Topics: Animals; Anti-Inflammatory Agents; Bronchoalveolar Lavage Fluid; Cytokines; I-kappa B Proteins; Interleukin-1beta; Iridoids; Lung; Male; Mice; Mice, Inbred BALB C; NF-kappa B; Peroxidase; Pneumonia; Signal Transduction; Staphylococcal Infections; Staphylococcus aureus; Tumor Necrosis Factor-alpha

Inflammasomes are cytoplasmic, multiprotein complexes that trigger caspase-1 activation and IL-1β maturation in response to diverse stimuli. Although inflammasomes play important roles in host defense against microbial infection, overactive inflammasomes are deleterious and lead to various autoinflammatory diseases. In the current study, we demonstrated that genipin inhibits the induction of IL-1β production and caspase-1 activation by NLRP3 and NLRC4 inflammasomes. Furthermore, genipin specifically prevented NLRP3-mediated, but not NLRC4-mediated, ASC oligomerization. Notably, genipin inhibited autophagy, leading to NLRP3 and NLRC4 inflammasome inhibition. UCP2-ROS signaling may be involved in inflammasome suppression by genipin. In vivo, we showed that genipin inhibited NLRP3-dependent IL-1β production and neutrophil flux in LPS- and alum-induced murine peritonitis. Additionally, genipin provided protection against flagellin-induced lung inflammation by reducing IL-1β production and neutrophil recruitment. Collectively, our results revealed a novel role in inhibition of inflammatory diseases for genipin that has been used as therapeutics for centuries in herb medicine.

Topics: Animals; Apoptosis Regulatory Proteins; Autophagy; Calcium-Binding Proteins; CARD Signaling Adaptor Proteins; Carrier Proteins; Caspase 1; Chemokines; Cytokines; Disease Models, Animal; Flagellin; Inflammasomes; Ion Channels; Iridoids; Lipopolysaccharides; Macrophage Activation; Macrophages; Mice; Mice, Knockout; Mitochondrial Proteins; NLR Family, Pyrin Domain-Containing 3 Protein; Peritonitis; Pneumonia; Protein Multimerization; Reactive Oxygen Species; Uncoupling Protein 2

Allergic inflammation of the airways has a critical role in asthma development. We investigated a suppressive effect of verproside (3,4-dihydroxy catalpol) isolated from the extract of Pseudolysimachion longifolium on asthmatic parameters--such as immunoglobulin E (IgE) level, cytokine release, eosinophilia, airway hyperresponsiveness and mucus hypersecretion--in an OVA-sensitized/challenged mouse model. Verproside significantly inhibited the increase of total IgE and the cytokines IL-4 and IL-13 in plasma and bronchoalveolar lavage fluid, and also effectively suppressed airway hyperresponsiveness, eosinophilia and mucus hypersecretion in OVA-induced asthmatic mice. The efficacy of verproside was comparable to montelukast, an anti-asthmatic drug that is currently available. These results suggest that verproside could be a major marker in herbal medicines that are used for asthma treatment, and could also act as a lead for anti-asthmatic drugs.

Topics: Acetates; Animals; Anti-Asthmatic Agents; Asthma; Bronchoalveolar Lavage Fluid; Cyclopropanes; Disease Models, Animal; Female; Glucosides; Immunoglobulin E; Interleukin-13; Interleukin-4; Iridoid Glucosides; Iridoids; Lung; Methacholine Chloride; Mice; Mice, Inbred BALB C; Molecular Structure; Mucus; Ovalbumin; Plant Extracts; Pneumonia; Pulmonary Eosinophilia; Quinolines; Sulfides; Veronica