Phloretin Attenuates Allergic Airway Inflammation and Oxidative Stress in Asthmatic Mice

Phloretin, isolated from the apple tree, was previously demonstrated to have anti-oxidative and anti-inflammatory effects in macrophages and anti-adiposity effects in adipocytes. Inflammatory immune cells generate high levels of reactive oxygen species for stimulated severe airway hyperresponsiveness (AHR) and airway inflammation. In this study, we investigated whether phloretin could reduce oxidative stress, airway inflammation, and eosinophil infiltration in asthmatic mice, and ameliorate oxidative and inflammatory responses in tracheal epithelial cells. BALB/c mice were sensitized with ovalbumin (OVA) to induce asthma symptoms. Mice were randomly assigned to the five experimental groups: normal controls; OVA-induced asthmatic mice; and OVA-induced mice injected intraperitoneally with one of the three phloretin doses (5 mg/kg, 10 mg/kg, or 20 mg/kg). In addition, we treated inflammatory human tracheal epithelial cells (BEAS-2B cells) with phloretin to assess oxidative responses and the levels of proinflammatory cytokines and chemokines. We found that phloretin significantly reduced goblet cell hyperplasia and eosinophil infiltration, which decreased AHR, inflammation, and oxidative responses in the lungs of OVA-sensitized mice. Phloretin also decreased malondialdehyde levels in the lung, and reduced Th2 cytokine production in bronchoalveolar lavage fluids. Furthermore, phloretin reduced reactive oxygen species, proinflammatory cytokines, and eotaxin production in BEAS-2B cells. Phloretin also suppressed monocyte cell adherence to inflammatory BEAS-2B cells. These findings suggested that phloretin alleviated pathological changes, inflammation, and oxidative stress by inhibiting Th2 cytokine production in asthmatic mice. Phloretin showed therapeutic potential for ameliorating asthma symptoms in the future.