Bufei Yishen formula alleviates airway epithelial cell senescence in COPD by activating AMPK-Sirt1-FoxO3a pathway and promoting autophagy

The Bufei Yishen formula (BYF) has traditionally been employed to treat patients with COPD, demonstrating significant effectiveness. However, the underlying mechanisms through which BYF alleviates COPD remains unclear. Cellular senescence is crucial in the pathogenesis of COPD. This study aims to investigate whether the therapeutic mechanism of BYF is associated with the reduction of cellular senescence. To evaluate the anti-senescence effects of BYF, a COPD rat model and a cellular senescence model were established. The active compounds and underlying mechanisms of BYF were investigated in vitro. BYF treatment significantly mitigated lung function decline and pathological damage in COPD rats. It significantly inhibited senescence in lung tissue by decreasing the expression of the cell cycle inhibitor p21, DNA damage markers, pro-inflammatory cytokines, and matrix metalloproteinases. BYF4/5, isolated from BYF, demonstrated significant anti-senescence effects in bronchial epithelial cells. Additionally, 67 compounds were identified from BYF4/5, and 770 targets were predicted for these compounds. hesperidin and nobiletin, identified as key compounds in BYF, were found to inhibit cellular senescence and activate the AMPK-Sirt1-FoxO3a pathway and autophagy in 16HBE cells. The data indicate that BYF alleviates COPD by activating the AMPK-Sirt1-FoxO3a pathway and autophagy, thereby inhibiting bronchial epithelial cell senescence.