Phytochemical investigation of Jie-Geng-Tang and regulatory role in the TNF-α pathway in mitigating pulmonary fibrosis using UPLC-Q-TOF/MS

Jie-Geng-Tang (JGT), composed of Platycodon grandiflorus (Jacq.) A. DC and Glycyrrhiza uralensis Fisch, is widely used in traditional Chinese medicine for its potential effects in preventing pulmonary fibrosis (PF). This study systematically explored the effects of JGT's water and 70% EtOH extracts in bleomycin (BLM)-induced PF models. In vitro, the 70% EtOH extract significantly reversed BLM-induced reductions in cell viability and apoptosis, whereas the water extract had limited impact. In vivo, the EtOH extract markedly reduced fibrosis markers, such as α-SMA and collagen-I, alleviating lung tissue damage and collagen deposition. UPLC-Q-TOF/MS analysis revealed that the EtOH extract contained a higher abundance of flavonoids compared to the water extract. Through network pharmacology analysis of the EtOH extract, four key flavonoids-apigenin, kaempferol, kaempferol 3-glucuronoside, and quercetin-were identified as crucial compounds. These flavonoids were found to reverse BLM-induced cell viability loss, with apigenin showing the most pronounced effect by modulating the TNF-α signaling pathway and inhibiting caspase-3 activation. Apigenin, as a primary active component derived from JGT, holds significant potential as a preventive agent against pulmonary fibrosis.