Comprehensive Investigation of Sweroside Metabolism in Rats Using a De Novo Strategy Based on Ultra-High-Performance...

Area of Science:

• Pharmacology and Drug Metabolism
• Natural Products Chemistry
• Analytical Chemistry

Background:

• Sweroside, a secoiridoid glycoside from medicinal plants, exhibits anti-tumor, anti-inflammatory, and hepatoprotective effects.
• Limited systemic exposure hinders the full understanding of sweroside's pharmacological potential.
• Investigating sweroside's metabolic fate is crucial for its therapeutic application.

Purpose of the Study:

• To elucidate the in vivo metabolic pathways and excretion of sweroside in rats.
• To identify and characterize sweroside metabolites using advanced analytical techniques.
• To develop an efficient strategy for profiling the metabolism of specific natural compounds.

Main Methods:

• Oral administration of sweroside to rats followed by collection of plasma, urine, and feces.
• Ultra-high-performance liquid chromatography/Quadrupole-Exactive mass spectrometry (UHPLC/Q-Exactive MS) for data acquisition.
• Data-dependent, dynamic exclusion, and parallel reaction monitoring (PRM) scan modes for database construction and metabolite identification.

Main Results:

• Sweroside is extensively metabolized in rats, with 18 identified metabolites, including nine novel ones.
• Predominant Phase II metabolic transformations include glycosylation, sulfonation, glucuronidation, and deglycosylation.
• Renal excretion is the primary route, with potential N-heterocyclization catalyzed by intestinal bacteria.

Conclusions:

• This study provides a comprehensive understanding of sweroside's in vivo metabolism and elimination in rats.
• The identified metabolites and pathways offer insights into sweroside's pharmacological activity and potential toxicity.
• The developed analytical approach is effective for profiling the metabolism of complex natural products.