Deciphering the mechanism of Sang Ju Yin in ameliorating acute lung injury: An integrated systems pharmacology approach encompassing chemical composition analysis, network pharmacology, metabolomics, molecular docking and molecular biology

Abstract

Sang Ju Yin (SJY), a renowned traditional Chinese medicinal formula, has been widely utilized in acute lung injury (ALI) management. Yet, its underlying therapeutic mechanisms remain obscure. This study devised an innovative and integrated methodology, merging advanced chemical analysis with biological assays, to elucidate SJY's action mechanism in ALI treatment. Initially, UFLC-ESI-QTOF-MS was employed to precisely analyze SJY's chemical constituents. Subsequently, network pharmacology predicted potential targets and signaling pathways for SJY's beneficial effects. In parallel, pharmacodynamic evaluation was performed on ALI rats. Utilizing LC-MS and ¹H NMR metabolomics techniques with an innovative data fusion strategy, potential biomarkers and perturbed metabolic pathways were identified. Crucially, integrating network pharmacology and metabolomics insights yielded a holistic understanding of the mechanism. Finally, verification experiments involving molecular docking, Western Blot, and qRT-PCR were carried out. Notably, potential key bioactive components including apigenin were identified for SJY's anti-ALI activity. Marked perturbations in representative pathways such as arachidonic acid (AA) metabolism and PI3K-Akt pathway were obtained after SJY administration. Furthermore, integrated data spotlighted PTGS2, PLA2, and AA metabolism as pivotal, linking predicted targets and metabolic alterations for SJY in ALI treatment. In summary, this study uncovers SJY's mechanism in ALI treatment, presenting an advanced interdisciplinary framework. It deepens our comprehension of traditional Chinese medicine's role in ALI, setting a new standard for research at the chemistry-pharmacology interface.