ovalbumin and geniposide

Our group recently reported the strong anti-inflammatory effects of geniposide (Gen), a bioactive iridoid glucoside derived from gardenia jasminoides, in a mouse acute lung injury model. Herein, we hypothesized that Gen might also have potential therapeutic benefits in treatment of asthma, which was tested in a mouse model of ovalbumin (Ova)-induced allergic airway inflammation. Ova-sensitized and -challenged BALB/c mice, as compared with control animals, displayed airway hyperresponsiveness (AHR), bronchoalveolar lavage eosinophilia, mucus hypersecretion, and increased T help 2 (Th2)-associated cytokine and chemokine amounts, as well as serum Ova-specific immunoglobulin E (IgE) level. Being compared with the Ova-induced hallmarks of asthma, intraperitoneal Gen treatment prevented eosinophilic pulmonary infiltration, attenuated the increases in interleukin (IL)-4, IL-5, and IL-13, and reduced eotaxin and vascular cell adhesion molecule 1 (VCAM-1) expression. Also, Gen significantly ameliorated the Ova-driven airway hyperresponsiveness, mucus hypersecretion, and allergen-specific IgE level, which are the cardinal pathophysiological symptoms in allergic airway diseases. In addition, the efficacy of Gen was comparable to that of dexamethasone (Dex), a currently available anti-asthmatic drug. Collectively, our findings reveal that the development of immunoregulatory strategies based on Gen may be considered as an effective adjuvant therapy for allergic asthma.

Topics: Allergens; Animals; Anti-Asthmatic Agents; Anti-Inflammatory Agents; Asthma; Bronchial Hyperreactivity; Bronchoalveolar Lavage Fluid; Cell Count; Cytokines; Disease Models, Animal; Female; Immunoglobulin E; Iridoids; Lung; Mice; Mice, Inbred BALB C; Ovalbumin

The primary objective of this study was to investigate the effect of geniposide, a potent anti-inflammatory, on ovalbumin-antigen-induced tracheal permeability and transepithelial electrical resistance in guinea pigs. Two weeks after sensitization with ovalbumin (100 mg/ml), the permeability of guinea-pig tracheas was evaluated by flux measurements using the transcellular tracer, [(14)C]estradiol, and the paracellular tracer, [(14)C]mannitol. The effect of extracellular Ca(2+) with geniposide was also studied, using deletion of Ca(2+) in the donor chamber. The in vivo treatment effect of aerosolized geniposide on tracheal permeability in the ovalbumin-sensitized guinea pigs was also evaluated. The results indicate that tight junction permeability of ovalbumin-sensitized trachea was significantly dose dependent and decreased by geniposide (1-10 mM), as evidenced by substantial recovery of transepithelial electrical resistance and decreased transepithelial permeability of [(14)C]mannitol at (1.32+/-0.12) x 10(-5) cm/s. The effect of combination of the removal of extracellular Ca(2+) with geniposide had no effect on tight junction permeability of ovalbumin-sensitized trachea and revealed that transepithelial electrical resistance and junction permeability did not recover. In addition, the cAMP levels and phosphodiesterase activity were not significantly influenced in ovalbumin-sensitized tracheal tissues after geniposide treatment. Inhaled geniposide (50 mM, 30 min after ovalbumin sensitization) significantly restored junction permeability induced by ovalbumin (100 mg/ml, 2 min). Junction permeability did not recover on pretreatment with geniposide (50 mM for 30 min over 16 days consecutive before ovalbumin sensitization) after exposure of conscious guinea pigs to aerosol ovalbumin. In conclusion, geniposide has inhibitory effects on ovalbumin-induced junction permeability and recovery of transepithelial electrical resistance in guinea pig trachea, showing its potential as anti-asthma therapy.

Topics: Aerosols; Animals; Anti-Inflammatory Agents; Calcium; Cyclic AMP; Guinea Pigs; Iridoids; Male; Mannitol; Ovalbumin; Permeability; Pyrans; Tight Junctions; Trachea