Pharmacokinetic evidence on the contribution of intestinal bacterial conversion to beneficial effects of astragaloside IV, a marker compound of astragali radix, in traditional oral use of the herb.
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 the 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 the main components in plasma following AIV, and the AUC(0-∞) were 88.60 ± 9.66 (CA), 179.06 ± 28.53 (CA-iso) and 452.28 ± 43.33 nM·h (AIV). CA-2H was the predominant form in feces but was not detected in urine or plasma. This agreed well with in vitro data including 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 the traditional application of Astragali herb and warrant further investigational emphasis on CA and CA-iso.
State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
Rui-Na
RN
Zhou
Yue-Lin
YL
Song
Jian-Qing
JQ
Ruan
Yi-Tao
YT
Wang
Ru
R
Yan
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D001419:Bacteria / Q000378:metabolism*; D001711:Biotransformation / Q000502:physiology; D004365:Drugs, Chinese Herbal / Q000493:pharmacokinetics*; D005243:Feces / Q000737:chemistry; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012502:Sapogenins / Q000378:metabolism; D012503:Saponins / Q000493:pharmacokinetics*; D014315:Triterpenes / Q000493:pharmacokinetics*
C543477:Astragali compound; D004365:Drugs, Chinese Herbal; D012502:Sapogenins; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; C061014:cycloastragenol