Metabolomic variability in Bupleurum root tea granules predicts sepsis pathway modulation

Introduction: Commercial Bupleurum root tea granule (BRTG) products may differ in chemical composition, but the biological relevance of this variability remains unclear, especially in sepsis-induced acute lung injury. Materials and methods: Untargeted metabolomics was used to compare six commercial BRTG products. Representative differential metabolites were then examined in relation to putative sepsis-related targets using network pharmacology, transcriptomic analysis of a public sepsis dataset, protein–protein interaction analysis, enrichment analysis, and molecular docking. Results: Untargeted metabolomics identified 90 annotated metabolites, including 77 detected in positive ionization mode and 13 in negative ionization mode. Principal component analysis (PCA) showed clear inter-brand separation, with PC1 and PC2 explaining 48.5% and 14.6% of the variance, respectively. Transcriptomic analysis identified 3064 differentially expressed genes (DEGs) in sepsis, including 1234 upregulated and 1830 downregulated genes, of which 200 overlapped with predicted BRTG targets. Representative differential metabolites were linked to targets such as tumor necrosis factor (TNF), interleukin 6 (IL6), signal transducer and activator of transcription 3 (STAT3), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and B-cell lymphoma 2 (BCL2). Enrichment analysis suggested involvement in inflammatory, oxidative, apoptotic, immune-metabolic, and barrier-related pathways. Molecular docking supported the possibility of compound-target interactions, with the strongest predicted binding reaching −9.9 kcal·mol−1. Conclusions: This study provides an exploratory framework linking inter-brand chemical variability in BRTG with disease-relevant targets and pathways in sepsis-induced acute lung injury. Although the findings remain predictive, they suggest that chemical consistency may be relevant to the biological evaluation and future standardization of multi-herb formulations.