Abstract
Astragaloside IV (AIV) is the most abundant saponin and a marker compound in Astragali Radix, a Chinese herb notable for its anti-aging and immune enhancing effects. The present study investigated the role of intestinal bacterial conversion in in vivo fate of AIV administered through a traditional oral route for the first time. When incubated anaerobically with rat intestinal bacteria, AIV generated five metabolites with three (monoglycosides brachyoside B and cyclogaleginoside B, the aglycone cycloastragenol (CA)) via stepwise deglycosylation and two from further epimerization (CA-iso) and dehydrogenation (CA-2H). Hydrolytic removal of C-6 glucose was a rate-limiting step for formations of CA and its derivatives. When AIV was orally administered to the rat, CA and CA-iso presented as main components in plasma following AIV and the AUC0-∞ were 79.79±10.81 (CA), 164.73±26.75 (CA-iso) and 565.10±126.29 nM⋅h (AIV). CA-2H was the predominant form in feces but not detected in urine and plasma. This agreed well with rapid hepatic metabolism of CA-2H to form CA and CA-iso and reversible conversions between CA-2H and CA/CA-iso by intestinal bacteria. These findings support a crucial role of gut bacterial conversion of AIV in traditional application of Astragali herb and warrant further investigational emphasis on CA and CA-iso.
