Metabolic Fate of Fraxin Administered Orally to Rats

• Published in: Journal of natural products (Washington, D.C.) Vol. 69; no. 5; pp. 755 - 757
• Main Authors: Yasuda, Takaaki, Fukui, Mai, Nakazawa, Takahiro, Hoshikawa, Ayumi, Ohsawa, Keisuke
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 01.05.2006; Amer Chemical Soc; American Society of Pharmacognosy
• Subjects: Animals; Biological and medical sciences; biotransformation; Chemistry, Medicinal; coumarins; Coumarins - administration & dosage; Coumarins - metabolism; Coumarins - pharmacology; Coumarins - urine; demethylation; Feces - chemistry; fraxin; Fraxinus; Fraxinus japonica; General pharmacology; glucuronidation; human health; hydrolysis; intestines; Intestines - drug effects; Intestines - microbiology; Life Sciences & Biomedicine; liver; Liver - metabolism; Male; Medical sciences; medicinal plants; Methylation; Molecular Structure; oral administration; Oriental traditional medicine; Pharmacognosy. Homeopathy. Health food; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Plant Sciences; Rats; Rats, Sprague-Dawley; Science & Technology; sulfation; Japan; O-DEMETHYLATION; BIOTRANSFORMATION; HUMAN LIVER-MICROSOMES; SCOPARONE; Chemical analysis; Rat; Metabolite; Coumarine derivatives; Enzymatic hydrolysis; Aglycone; HPLC chromatography; Glucuroconjugate; Biological material; Demethylation; Glycoside; Feces; Urine; Rodentia; Elimination; Oral administration; Lactone; Metabolism; Sulfatation; Vertebrata; Antibiotic; Mammalia; Animal; Methylation; Pharmacokinetics
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/np0580412

Naturally occurring fraxin (1) was administered orally to rats to investigate its metabolism. Urinary metabolites were analyzed by three-dimensional HPLC, and fraxetin-7-O-sulfate (2), fraxetin-7-O-β-glucuronide (3), fraxetin (4), 6,7,8-trihydroxycoumarin (5), and fraxidin (6) were isolated. Fraxin (1) was extensively metabolized to 4, which was partly metabolized to 5 in a rat fecal suspension after incubation for 24 h. Urinary excretion of 4 and 5 in rats administered orally with 1 was substantially reduced when the rats were treated with antibiotics to suppress their intestinal flora. Incubation of 1 with a rat liver S-9 mixture yielded 6. These results suggest that hydrolysis and demethylation of 1 are performed by intestinal microflora, while methylation occurs in the liver.