Polydatin attenuates reactive oxygen species-induced airway remodeling by promoting Nrf2-mediated antioxidant...

Area of Science:

• Pulmonary Medicine
• Pharmacology
• Cell Biology

Background:

• Asthma involves fibrotic airway remodeling driven by reactive oxygen species (ROS) and epithelial-mesenchymal transition (EMT).
• Transforming growth factor-beta1 (TGF-β1) is a key mediator in this process.
• Polydatin (PD), a natural compound with antioxidant properties, is a potential therapeutic agent.

Purpose of the Study:

• To investigate the protective effects of Polydatin (PD) against ROS-induced pulmonary fibrosis in an asthma model.
• To determine if PD reverses TGF-β1-induced pulmonary epithelial cell EMT via Nrf2-mediated antioxidation.

Main Methods:

• An ovalbumin (OVA)-induced asthma mouse model was used, with some mice treated with PD.
• Nuclear factor erythroid 2-related factor 2 (Nrf2) knockdown BEAS-2B cells were created to study PD's mechanism.
• Immunofluorescence, immunohistochemistry, and Western blotting were employed to analyze ROS, TGF-β1, EMT markers, and Nrf2 pathway activation.

Main Results:

• OVA-induced asthma models showed increased ROS and TGF-β1 levels in lung tissue, which PD treatment inhibited.
• PD treatment reduced lung ROS, TGF-β1 expression, and fibroblast accumulation.
• PD reversed OVA-induced EMT and suppressed fibroblast protein expression by promoting Nrf2-mediated antioxidant enzyme expression (heme oxygenase-1 and NADPH dehydrogenase (quinone)-1).

Conclusions:

• Polydatin (PD) demonstrates therapeutic potential for asthma by mitigating ROS-induced pulmonary fibrosis.
• PD's protective effects are mediated through the Nrf2 pathway, enhancing antioxidant capacity and suppressing EMT.
• Nrf2 downregulation negates PD's beneficial effects, highlighting its crucial role in PD's mechanism of action.