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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.

Rationale Traditional Chinese medicines (TCMs) attract worldwide attention because of their effects in clinical application recorded in China historical ancient codes and in records, such as 'Treatise on Febrile Diseases'. With the developments of drug analysis and research, evaluating the in vivo substances in TCMs has become of great importance. Scutellariae Radix (SR, named as huang-qing in China), the root of Scutellaria baicalensis Georgi, has shown favorable clinical effects and safety in the treatment of infection diseases; however, its in vivo compounds are unclear and need detailed investigation. Methods An ultra-high-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UHPLC/QTOF MS) method coupled to an integrated strategy involving diagnostic ions, neutral losses and a prediction platform was used to explore the constituents of SR, and their exogenous substances in rats. Results A total of 118 chemical constituents mainly featuring five chemical structure types (flavone C-glycosides, flavone O-glycosides, free flavones, flavanones and phenylethanoid glycosides) were identified or tentatively characterized in SR, and 175 xenobiotics (68 prototypes and 107 metabolites) were profiled in rat plasma, urine, bile and feces after ingestion of SR. The metabolites were classified into four related chemical groups: flavone C-glycosides, flavone O-glycosides, flavanones and phenylethanoid glycosides. Phase II metabolism reactions, such as glucuronidation and sulfation, were the major metabolic reactions in addition to phase I reactions of hydrolysis and hydrogenation. The corresponding main metabolic features of SR in rats were also elucidated. Conclusions The metabolism of SR, as a whole, was systemically revealed for the first time, and our work also provided meaningful information for pharmacokinetics studies and pharmacological analysis of SR in future work.

A target and nontarget strategy based on in-house chemical components library was developed for rapid and comprehensive analysis of complicated components from traditional Chinese medicine preparation Shuang-Huang-Lian oral liquid. The sample was analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry using generic acquisition parameters. Automated detection and data filtering were performed on the UNIFI™ software and the detected peaks were evaluated against an in-house library. As a result, a total of 170 chemical components (110 target compounds and 60 nontarget ones) were identified or tentatively characterized, including 54 flavonoids, 30 phenylethanoid glycosides, 16 iridoid glycosides, 14 lignans, 32 organic acids, 19 triterpenoid saponins and five other types of compounds. Among them, 44 compounds were further confirmed by comparison with reference standards. It was demonstrated that this systematical approach could be successfully applied for rapid identification of multiple compounds in traditional Chinese medicine and its preparations. Furthermore, this work established the foundation for the further investigation on the metabolic fates of multiple ingredients in Shuang-Huang-Lian oral liquid.