[UPLC-Q-TOF-MS-based metabolomics study of celastrol]

Area of Science:

• Pharmacology
• Metabolomics
• Drug Metabolism

Background:

• Celastrol is a compound with potential therapeutic applications.
• Understanding its metabolism and effects on endogenous metabolites is crucial for its development.

Purpose of the Study:

• To systematically investigate the formation of celastrol metabolites in vivo.
• To explore the impact of celastrol on endogenous metabolites.
• To identify key metabolic enzymes and affected pathways.

Main Methods:

• Mass spectrometry-based metabolomics, including UPLC-QTOF-MS.
• Oral administration of celastrol to mice and collection of plasma, urine, and feces.
• Mass defect filtering and multivariate statistical analysis.

Main Results:

• Eight celastrol metabolites were detected in mouse urine and feces, with five reported as novel.
• Hydroxylated metabolites were identified, with CYP3A4 confirmed as the major metabolic enzyme.
• Celastrol altered the excretion of several gut bacteria-related endogenous metabolites.

Conclusions:

• The study elucidates the in vivo metabolism and disposition of celastrol.
• Identified metabolites and affected pathways provide insights into celastrol's mechanism of action.
• Findings support further investigation of celastrol as a therapeutic agent.