Material basis and mechanism of Tangzhiqing in alleviating diabetic atherosclerosis: integrated serum pharmacochemistry, pharmacokinetics, metabolomics, bile acid profiling and 16S rRNA sequencing study
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE: Diabetic atherosclerosis (DA), characterized by disordered glucose and lipid metabolism, represents a significant metabolic vascular complication. Tangzhiqing (TZQ) has traditionally been used to treat diabetes and its complications. However, its material basis and mechanism for DA remain require further investigation.
AIM OF STUDY: This research aimed to systematically elucidate the pharmacological material basis and underlying mechanism of the traditional Chinese medicine TZQ in diabetic atherosclerosis model mice.
MATERIALS AND METHODS: This study established UPLC-MS/MS and UPLC-Q-TOF/MS methods to detect composition and content of TZQ in vivo and in vitro, with pharmacokinetic analysis determining plasma concentration changes of representative components. DA model was induced by western diet and streptozotocin injection in ApoE-/- mice. Mice received TZQ (2.5 g/kg) for 12 weeks, with metformin as a positive control. Anti-DA effects were evaluated through blood glucose, lipid profiles, and aortic histopathology. Metabolomics and network pharmacology identified key therapeutic pathways. Targeted bile acid metabolomics and 16S rRNA sequencing were employed to assess bile acid profiles in 3 and gut microbiota composition. Subsequent western blot analysis and molecular docking experiments validated the effects of TZQ on key proteins including FXR and CYP7A1.
RESULTS: 118 compounds were identified from TZQ. It contains categories such as organic…
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