Mechanistic Insights into Ginkgo Biloba Extract's Anti-Inflammatory Effects in COPD: Regulation of Th1/Th2 Balance via the p38 MAPK Pathway

OBJECTIVE: To investigate the anti-inflammatory and therapeutic effects of Ginkgo biloba extract (GBE) on chronic obstructive pulmonary disease (COPD), and to elucidate the underlying molecular mechanism by which GBE modulates the p38 mitogen-activated protein kinase (MAPK) signaling pathway and maintains the balance of T helper 1 (Th1)/T helper 2 (Th2) cells, thereby alleviating pulmonary inflammation, alveolar destruction and airway remodeling in COPD. METHODS: Rats were randomly assigned to one of six groups: a blank group, a COPD model group, a high-dose GBE group (14 mg/kg/day), a medium-dose GBE group (7 mg/kg/day), a low-- dose GBE group (3.5 mg/kg/day), and a p38 MAPK inhibitor group, with 15 rats in each group. Except for the blank group, COPD models were established in the other groups using cigarette smoke (CS) inhalation combined with intratracheal lipopolysaccharide (LPS) instillation. Following the establishment of the models, the respective treatments were administered to each group. After the drug interventions, histological examination using HE staining, enzyme-linked immunosorbent assay (ELISA), flow cytometry, quantitative real-time polymerase chain reaction (PCR), and Western blot analysis were performed to explore the underlying mechanisms. RESULTS: Different doses of GBE and the p38 MAPK inhibitor alleviated alveolar destruction and airway remodeling in COPD rats, reducing inflammatory infiltration around alveoli and bronchi. Compared with the COPD model group, all GBE dose groups and the p38 MAPK inhibitor group inhibited p38 MAPK signaling and the activation of upstream regulatory factors (TLR3, MKK3, MKK6) (p