Metabolic Fate of (−)-[4-³H]Epigallocatechin Gallate in Rats after Oral Administration

Abstract

After oral administration of [4-(3)H]EGCg to rats, the radioactivity in blood, major tissues, urine, and feces was measured over time. The radioactivity in blood and most tissues remained low for 4 h postdose, began to increase after 8 h, peaked at 24 h, and then decreased. Major urinary excretion of radioactivity occurred in the 8-24 h period, and the cumulative radioactivity excreted by 72 h was 32.1% of the dose. The radioactivity in the feces was 35.2% of the dose within 72 h postdose. In the case of rats pretreated with antibiotics (antibiotic-pretreated rats), the radioactivity levels of the blood and urine were definitely lower than those in rats not pretreated with antibiotics (normal rats). The radioactivity recovered in the antibiotic-pretreated rat urine was estimated to be only (1)/(100) of that in the normal rat urine. These results clearly demonstrated that the radioactivity detected in the blood and urine of normal rats mostly originated from degradation products of EGCg produced by intestinal bacteria. Furthermore, a main metabolite in the normal rats was purified and identified as 5-(5'-hydroxyphenyl)-gamma-valerolactone 3'-O-beta-glucuronide (M-2). In feces of the normal rats, EGC (40.8% of the fecal radioactivity) and 5-(3',5'-dihydroxyphenyl)-gamma-valerolactone (M-1, 16.8%) were detected. These results suggested that M-1 was absorbed in the body after degradation of EGCg by intestinal bacteria, yielding M-1 with EGC as an intermediate. Furthermore, M-2 was thought to be formed from M-1 in the intestinal mucosa and/or liver, then to enter the systemic circulation, and finally to be excreted in the urine. Taking into account all of the above findings, a possible metabolic route of EGCg orally administered to rats is proposed.

Contribution of Presystemic Hepatic Extraction to the Low Oral Bioavailability of Green Tea Catechins in Rats

“…Novel metabolites of EGC and EC have been identified in human plasma and urine and appeared to be produced by intestinal microorganisms . Sulfate and glucuronide conjugates of green tea catechins have been identified in preclinical and clinical samples (Okushio et al, 1999;Yang et al, 1999;Chow et al, 2001;Kohri et al, 2001). UDP-glucuronosyltransferase and phenolsulfotransferase located in the intestinal mucosa could be responsible for the presystemic gut wall metabolism of green tea catechins.…”

Potentiation of Catechin Gallate-Mediated Sensitization of Staphylococcus aureus to Oxacillin by Nongalloylated Catechins

“…This pairing is effective because clavulanate inhibits the ␤-lactamase that would otherwise inactivate amoxicillin. Previous studies have shown that the gallate group is essential for epicatechin gallate activity (12); it is attached to the catechin moiety via an ester linkage that has the potential for cleavage by bacterial esterases (9). However, as EC and EGC lack the gallate group, it is unlikely that they act as esterase inhibitors.…”

Biotransformation of (−)-Epigallocatechin and (−)-Gallocatechin by Intestinal Bacteria Involved in Isoflavone Metabolism

“…1) However, since absorption of intact EGCg in the body has been reported to be very low, 2,3) it was considered to be important to elucidate its metabolic pathway in the gut tract in order to obtain further understanding of its physiological functions. We previously reported on the degradation of EGCg by rat intestinal microflora, identification of its metabolites, and its metabolic pathway in the gut tract.…”