Disposition of Astragaloside IV via Enterohepatic Circulation Is Affected by the Activity of the Intestinal Microbiome.

Astragaloside IV (ASIV) is a typical bioactive constituent of Radix Astragali. The study aimed to investigate the enterohepatic circulation of ASIV and evaluate the impact of activity of intestinal microbiota on the deposition of ASIV. The amounts of ASIV and its metabolites were quantified by an LC-MS/MS method. ASIV was metabolized by intestinal bacteria to form brachyoside B (Bra B), cyclogaleginoside B (Cyc B), cycloastragenol (CA), iso-cycloastragenol (iso-CA), and dehydrogenated metabolite of CA (CA-2H). CA and iso-CA circulated in blood besides ASIV when rats received ASIV intragastrically or intravenously. After rats were intragastrically administered 10 mg/kg ASIV, the AUC0–t values of ASIV, CA, and iso-CA were 109 ± 55, 26.8 ± 17.9, and 77.9 ± 35.1 nM·h, respectively. The plasma distribution of ASIV was significantly affected by bile duct drainage when ASIV was administered through the duodenum. ASIV, Bra B, and Cyc B were secreted from bile after duodenal administration of ASIV. Antibiotics mar...