iridoids and Hyperoxia

Bronchopulmonary dysplasia is the most common chronic lung disease of infancy and is associated with pulmonary hypertension (PH). Inhibition of glycogen synthase kinase (GSK)-3 β has been shown to attenuate lung injury and PH in hyperoxia-exposed newborn rats. Genipin has been widely used for the treatment of inflammatory diseases. The aim of this study was to show that genipin decreased the expression of GSK-3 β in lung tissues of hyperoxia-exposed rat pups.. We established models of hyperoxia-exposed rat pups, evaluated lung injury and pulmonary hypertension and detected the mRNA and protein expression of key molecules.. Hyperoxia resulted in the reduction of survival rate and histologic injury of lung tissues; an increase of the messenger RNA (mRNA) expression of transforming growth factor-β1, extracellular matrix proteins collagen-I and fibronectin, and α-smooth muscle actin; an increase of right ventricular (RV) systolic pressure and the weight ratio of RV to left ventriclar (LV) plus septum (S) (RV/LV + S) were inhibited by genipin. Genipin also decreased the levels of tumor necrosis factor-α, interleukin-1 β, and interleukin-6 in both bronchoalveolar lavage fluid and lung tissues after hyperoxia exposure. In addition, genipin inhibited p65 nuclear factor-κB nuclear translocation and matrix metalloproteinase-2 and -9 expression. Moreover, hyperoxia resulted in an increase of methane dicarboxylic aldehyde content and a decrease of superoxide dismutase activity, catalytic subunit of glutamate-cysteine ligase, modified subunit of glutamate-cysteine ligase, and nuclear factor erythroid 2-related factor 2 expression were inhibited by genipin. All these effects induced by genipin were blocked by upregulation of GSK-3 β. Genipin downregulated GSK-3 β expression, decreased nuclear factor-κB translocation, increased nuclear factor erythroid 2-related factor 2 expression, attenuated inflammation and oxidative stress, leading to amelioration of lung injury and PH in hyperoxia-exposed rat pups.. Overall, genipin may provide a novel therapeutic option for preventing and treating infants with bronchopulmonary dysplasia.

Topics: Animals; Animals, Newborn; Anti-Inflammatory Agents; Antioxidants; Bronchopulmonary Dysplasia; Disease Models, Animal; Gardenia; Glycogen Synthase Kinase 3 beta; Humans; Hyperoxia; Hypertension, Pulmonary; Infant, Newborn; Interleukins; Iridoids; Lung; Lung Injury; NF-E2-Related Factor 2; NF-kappa B; Oxygen; Phytotherapy; Plant Extracts; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha