ABSTRACT This study aimed to investigate the prophylactic and therapeutic effects of Sulforaphane (SFN) on PM 2.5 ‐induced chronic obstructive pulmonary disease (COPD) and to elucidate the underlying mechanisms. A PM 2.5 ‐induced COPD rat model was established. The protective effects of SFN, administered concurrently with PM 2.5 exposure, were evaluated by analyzing inflammatory cytokine levels and performing histopathological examinations of lung tissues. The antioxidant role of SFN in COPD was further investigated both in vivo and in vitro via the Nrf2 signaling. Subsequently, potential targets and underlying mechanisms of SFN in COPD treatment were predicted through network pharmacological analyses. Molecular docking simulations were then performed to validate the binding affinities between SFN and key target proteins. Furthermore, the modulatory effects of SFN on the EGFR/PI3K/AKT signaling in PM 2.5 ‐induced COPD were investigated both in vivo and in vitro, and EGFR silencing was subsequently used to confirm the involvement of this pathway. Finally, the therapeutic efficacy of SFN in attenuating PM 2.5 ‐exacerbated COPD progression was evaluated through histopathological examination and assessment of Nrf2 and EGFR/PI3K/AKT pathway activation. SFN significantly attenuated PM 2.5 ‐induced lung injury, inflammation, mucus hypersecretion, and redox stress. Mechanistically, SFN directly activated the Nrf2 signaling, reduced reactive oxygen species (ROS) generation, and thereby mitigated COPD progression. Integrated network pharmacology and molecular docking analyses further identified EGFR as a potential key target of SFN. Consistently, SFN could directly bind to EGFR and suppress EGFR/PI3K/AKT signaling, contributing to its prophylactic effects. Moreover, in the rat AECOPD model, SFN exerted therapeutic benefits primarily via EGFR/PI3K/AKT inhibition, with minimal involvement of Nrf2‐driven antioxidant effects. Here, these findings reveal a dual mechanism by which SFN attenuates PM 2.5 ‐induced COPD via Nrf2 activation and inhibition of EGFR/PI3K/AKT signaling, thereby highlighting its potential as a promising candidate for COPD and its acute exacerbation.
Lin et al. (Mon,) studied this question.