Steroids and flavonoids in TRQ ameliorates chronic obstructive pulmonary disease involving Pink1/Parkin-mediated mitophagy

Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder linked to oxidative stress, mitochondrial damage, and impaired mitophagy. Tanreqing (TRQ) inhalation solution is widely used for respiratory diseases but its mechanism against COPD remains poorly defined. Here we investigated the protective effects of TRQ and its underlying pathway in a COPD rat model and cigarette smoke extract (CSE)-stimulated A549 cells. Our results showed that TRQ treatment alleviated body weight loss, lung pathological injury, alveolar destruction, and airway remodeling in rats. TRQ reduced ROS and MDA levels, restored SOD activity, and improved mitochondrial function including ATP production, mitochondrial membrane potential, and mitochondrial permeability transition pore homeostasis. Moreover, TRQ enhanced autophagy and mitophagy by upregulating Bnip3, Nix, Pink1, and Parkin expression. In vitro, knockdown of Pink1 abolished TRQ-mediated mitophagy activation, confirming that the Pink1/Parkin pathway was essential for TRQ action. In conclusion, TRQ inhalation solution ameliorates COPD by suppressing oxidative stress and restoring mitochondrial homeostasis via activating Pink1/Parkin-mediated mitophagy. This study identifies TRQ as a promising candidate for COPD treatment.