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Exploring Mechanism of Forsythia-4 Ingredients Decoction Alleviates Acute Lung Injury via the CEBPB/MAPK Signaling
Sachula Baoyin1, Xiong Ling2, DeSi AoBi1
1Department of Mongolian Medicine, Xilinguole Meng Mongolian General Hospital, Xilinhot 026000, China.
Introduction:
Forsythia-4 Ingredients Decoction (F4ID) is a classic traditional Mongolian medicine formulation (National Medicine Standard Z15021063) that has been included in the Mongolian medical diagnosis and treatment guidelines during the COVID-19 pandemic. This study aims to investigate the protective effect of traditional Mongolian medicine F4ID on bleomycin- induced acute lung injury in rats and its mechanism.
Methods:
The SD rats were used to establish an acute lung injury model through intratracheal instillation of bleomycin. The pharmacological effects of F4ID were evaluated through lung tissue case analysis, inflammatory cytokines, and general condition assessment. The chemical components of F4ID were analyzed using network pharmacology databases. Transcriptomics was employed to predict potential biological targets. Molecular docking validation was conducted to assess the binding affinity of the core components identified in the study with their respective targets.
Results:
In this study, we demonstrated that F4ID can improve pathological changes in lung injury and downregulate IL-6 and TNF-α levels. Additionally, we identified 49 active components in F4ID, including luteolin, and used transcriptomics to identify 107 Differentially Expressed Genes (DEGs), with the expression of Cebpb significantly downregulated. Additionally, GO and KEGG analyses indicated that the Mitogen-Activated Protein Kinase (MAPK) signaling pathway may be a molecular target. Molecular docking analysis showed a high targeting relationship between the components of F4ID, their targets, and pathways.
Discussion:
F4ID showed significant therapeutic effects on bleomycin-induced acute lung injury in rats, and its mechanism of action was related to the Cebpb and MAPK signaling pathways. Luteolin may be a potential active ingredient. This work also provides a reference for related research on traditional Mongolian medicine.
Conclusion:
The active ingredient luteolin in F4ID exerts a pulmonary protective effect by inhibiting Cebpb and MAPK signaling pathways in the lung tissue of ALI rats.