Integrating UHPLC-Q-TOF-MS/MS and Network Pharmacology to Reveal the Mechanism of Jinbei Oral Liquid in Radiation-Induced Lung Injury with Pulmonary Hypertension

Pulmonary fibrosis (PF) with pulmonary hypertension (PAH) commonly arises in advanced radiation-induced lung injury (RILI) stages. Jinbei Oral Liquid (JBOL) has certified in clinical studies to enhance pulmonary function indicators and 6MWD in PF patients. The clinical improvement impact on the comorbidity is obvious while its molecular mechanism remains unclear. In this study, Active fraction identification in lung tissues was conducted using UHPLC-Q-TOF-MS/MS. Potential targets of effective active compounds were predicted using TCMSP, SwissTargetPrediction, HERB, GeneCards and DrugBank. JBOL and RILI-PAH targets were obtained from GeneCards, DisGeNET, Harmonizome and GEO dataset. The herb-pathway-target-disease network and PPI of intersection targets were constructed using STRING and Cytoscape. We further performed GO and KEGG enrichment analysis on these targets. Molecular docking was performed to validate the docking activity of the core active compounds and targets. We tentatively annotated 34 prototype lung-inhaled components via UHPLC-Q-TOF-MS/MS. Network pharmacology may potentially alleviate RILI-PAH by utilizing active compounds like Daidzein, Calycosin, Cnidilide, Glycyrrhetinic acid, Hesperidin, Liquiritigenin, and Protocatechualdehyde to modulate targets such as PGF, IGF1, MMP9, MMP8, CCR1, ALOX5AP, and CCND1, and influence signaling pathways like PI3K-Akt, AGE-RAGE, and HIF-1. This intervention could impact inflammatory responses, promote cell migration and motility, and influence cellular reactions to nitrogen compounds. The molecular docking results showed that hesperdin, daidzein, calycosin and Glycyrrhetinic acid have higher affinity with CCR1, MMP8 and ALOX5AP. The results suggest that JBOL may treats RILI-PAH through multiple components and pathways, providing a clinical reference for the principle of treating different diseases with the same method.