Ginsenoside Rg1 Alleviates Chronic Obstructive Pulmonary Disease Partially Through Regulating ABCB1‐Mediated Mitochondrial Dysfunction

ABSTRACT To investigate the protective effects of ginsenoside Rg1 on lung injury in chronic obstructive pulmonary disease (COPD) and to elucidate the underlying mechanism involving ATP‐binding cassette subfamily B member 1 (ABCB1)‐mediated regulation of mitochondrial function. A COPD rat model was established by cigarette smoke exposure, followed by in vivo administration of different doses of ginsenoside Rg1. ABCB1 knockdown was achieved by tail vein injection of short hairpin RNA (shRNA). Hematoxylin and eosin (HE) and Masson staining were performed to evaluate lung histopathology and collagen deposition. Pulmonary function was assessed by measuring inspiratory resistance (Ri), dynamic lung compliance (Cdyn), and the ratio of forced expiratory volume at 0.3 s to forced vital capacity (FEV 0 . 3 /FVC). In vitro, cigarette smoke extract (CSE) was used to induce injury in human bronchial epithelial (HBE) cells, followed by Rg1 treatment and ABCB1 overexpression or knockdown. Advanced glycation end products–receptor for advanced glycation end products (AGEs–RAGE) and early growth response protein 1–c‐Jun N‐terminal kinase (EGR1–JNK) signaling pathways were detected. In COPD rats, Rg1 markedly attenuated alveolar structural destruction and collagen deposition, decreased Ri, increased Cdyn and FEV 0 . 3 /FVC. ABCB1 knockdown partially reversed these protective effects. In HBE cells, Rg1 enhanced cell viability, restored mitochondrial membrane potential, reduced apoptosis, decreased ROS accumulation, and rescued intracellular ATP depletion. Rg1 inhibited the activation of the AGEs–RAGE and EGR1–JNK pathways in a manner associated with upregulation of ABCB1 expression. Ginsenoside Rg1 enhances mitochondrial function partially through upregulation of ABCB1 expression, thereby alleviating mitochondrial dysfunction in COPD rats and CSE‐treated HBE cells.