A Bioactive Constituent from Bazhen Decoction Alleviates Sepsis-Associated Liver Injury by Restoring SLC6A6-Mediated Taurine Transport to Reprogram Macrophage Immunometabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Bazhen Decoction (BZD) is a classical formula first recorded in Ruizhu Tang Jing Yan Fang (14th century) and prescribed for centuries to replenish "Qi" and nourish "Blood". However, its bioactive constituents and immunometabolic mechanisms in sepsis-associated liver injury (SALI) remain unclear. AIM OF THE STUDY: To identify the key bioactive component of BZD and investigate its immunometabolic mechanism in SALI. MATERIALS AND METHODS: An integrated pipeline combining metabolomics, UPLC-Q-TOF-MS/MS, network pharmacology, and transcriptomics was followed by validation in septic mice induced by cecal ligation and puncture (CLP) and lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages using pharmacological modulation, including competitive inhibition of SLC6A6 transport with β-alanine and Seahorse XF metabolic flux analysis. RESULTS: Among 305 constituents, Suchilactone emerged as a key constituent. BZD treatment improved 7-day survival, reduced liver injury scores by 50-60%, and shifted hepatic macrophage polarization from M1 toward M2. Integrated omics profiling identified taurine as the central metabolic mediator. Suchilactone upregulated SLC6A6, restored intracellular taurine, and suppressed JAK1/STAT3 phosphorylation. It improved macrophage glycolytic and mitochondrial readouts, accompanied by increased PGC-1α, CPT1A, and ACOX1 expression consistent with enhanced fatty-acid-oxidation capacity. β-Ala co-treatment attenuated several Suchilactone-associated metabolic and polarization changes, providing supportive pharmacological evidence for possible involvement of taurine transport without establishing β-Ala specificity or causal SLC6A6 dependence. The liver-protective and macrophage-polarization findings were further observed in vivo. CONCLUSIONS: Suchilactone is associated with SLC6A6-mediated taurine transport to reprogram macrophage immunometabolism via JAK1/STAT3 suppression. These results indicate that the SLC6A6/taurine axis is a potential therapeutic target for sepsis-associated liver injury, and the causal contribution of this pathway requires further investigation.