Dissection of the potential anti-diabetes mechanism of salvianolic acid B by metabolite profiling and network pharmacology.

RATIONALE Salvianolic acid B (Sal B), the Q-marker in Salvia miltiorrhiza, was proved to present an obvious anti-diabetes effect when treating as a food intake. Till now, its metabolism feature, tissue distribution, and anti-diabetes mechanism of Sal B were not fully elucidated. METHODS The metabolites of Sal B in rats were profiled by an ultra-high-performance liquid chromatography coupled time-of-flight mass spectrometry (UHPLC/Q-TOF MS) method. The potential anti-diabetes mechanism of Sal B was predicted by network pharmacology. RESULTS A total of 31 metabolites were characterized in rats after ingestion of Sal B at a dosage of 40 mg/kg, including 1 in plasma, 19 in urine, 31 in feces, 0 in heart, 0 in liver, 0 in spleen, 1 in lung, 1 in kidney and 0 in brain. Among them, 18 metabolites were reported for the first time. Phase I reactions of hydrolysis, hydrogenation, dehydroxylation, hydroxylation, decarboxylation, isomerization, and phase II reactions of methylation were found in Sal B. Notably, decarboxylation and dehydroxylation were revealed in salvianolic acid B for the first time. The pharmacology network results showed that Sal B and its metabolites could regulate ALB, PLG, ACE, CASP3, MMP9, MMP2, and MTOR, etc. The above targets were involved in insulin signaling pathway, PI3K-Akt signaling pathway, HIF-1 signaling pathway, and TNF signaling pathway, etc. CONCLUSION: The metabolism feature of Sal B in vivo was systematically revealed, and its anti-diabetes mechanism for further pharmacological validations was predicted based on metabolite profiling and network pharmacology for the first time.