Oligomeric proanthocyanidin attenuates asthma severity and airway remodeling by modulating epithelial-smooth muscle cell interactions.

BACKGROUND: As a significant instigator of asthma pathogenesis, the airway epithelium produces cytokines that disrupt lung homeostasis and contribute to airway remodeling. Although efforts are directed in the management of this progress but few have proved effective. Recently, there is a cue that oligomeric proanthocyanidin (OPC), a widely used antioxidant supplement extracted from grape seeds with a broad safety margin, presents potential in asthmatic mice while the mechanism remains unclear.

PURPOSE: To elucidate the impacts of OPC on asthma and the potential mechanisms that may be involved.

STUDY DESIGN: Asthma patients, OVA-sensitized mice, human bronchial epithelial (BE) cells and airway smooth muscle (ASM) cells were included to explore the effect of OPC on asthma, with a particular focus on the underlying mechanism.

METHODS: 34 patients with asthma were enrolled in three treatment groups randomized to a standard budesonide/formoterol inhalation with or without the oral OPC supplementation for 8 weeks. BALB/c mice were sensitized and challenged with OVA to establish an asthmatic model, pretreated with or without OPC. BE cells were stimulated with TNF-α to mimic an inflammatory epithelial state in asthma, and ASM cells were incubated with the supernatant collected from BE cells to construct a conditioned co-culture system.

RESULTS: Patients supplemented with OPC showed more improvements in asthma control test scores, forced expiratory volume in one second, and peripheral eosinophil counts. In OVA-sensitized mice, OPC administration exhibited superior benefits in airway hyperresponsiveness, inflammation and remodeling, additionally with a suppression in malondialdehyde levels. Further analysis using an inflammatory epithelial cell model demonstrated that OPC reduced the secretion of epithelial-derived cytokines, including eotaxin-1 and TGF-β1. This reduction is likely due to the decreased intracellular ROS signal, which were confirmed by using H2O2 and the ROS scavenger N-acetylcysteine. With the co-culture of epithelial and airway smooth muscle cells, OPC was indicated to inhibit ASM cell proliferation by reducing epithelial-derived TGF-β1, potentially through the p38 pathway.

CONCLUSION: Our findings provide the first evidence that OPC may offer a promising approach to clinical asthma management by modulating communication between airway structural cells, highlighting the potential of OPC as a potent option to mitigate airway remodeling in asthma.