Metabolism and Absorption of Auraptene (7-Geranyloxylcoumarin) in Male SD Rats: Comparison With 7-Ethoxycoumarin

Abstract

We previously reported that auraptene (7-geranyloxycoumarin; AUR), a coumarin that occurs widely in citrus fruit, has been shown to be a promising cancer-preventive agent in several rodent models. However, its bioavailability and metabolism have not been investigated. In this study, we compared the metabolism characteristics of AUR with those of 7-ethoxycoumarin (ETC) in male Sprague Dawley rats. Each (500 micromol/kg body weight) was given separately by a single gastric intubation procedure, and digestive tract, liver, and kidney were removed at 1, 4, and 24 h after administration. The localization profiles of AUR and ETC in the gastrointestinal tract were similar. However, AUR, in contrast to ETC, showed significant localization in the liver from 1 to 4 h. Treatments of serum and urinary samples with glucuronidase/sulfatase led to the detection of significant amounts of umbelliferone (7-hydroxycoumarin; UMB), and serum and urinary concentrations of UMB following ETC administration were significantly higher than with AUR administration. Our results suggest that AUR, which bears a geranyloxyl side chain, has a longer life span than ETC, and this property may be associated with its previously reported chemopreventive and xenobiotics metabolizing activities.

Essential Oils and Antioxidants Derived From Citrus By-Products in Food Protection and Medicine: An Introduction and Review of Recent Literature

“…Tanaka, Yasui, Ishigamori-Suzuki, and Oyama (2008) note that, along with a number of other citrus oil components, it inhibits chronic inflammation and fat build up that predispose laboratory mice to chemically caused colon cancer. Kuki, Hosotani, Ohigashi, and Murakami (2008) note that auraptene stays in circulation longer and seems to have longer lasting effects in stimulating the breakdown of carcinogenic compounds in the kidneys and livers of several types of rodents in which cancers have been experimentally induced, a finding consonant with the results of Tanaka et al (1998), Prince et al (2009), andKleiner et al (2008) who also mention bergamottin in this context. Most recently (Krishnan et al, 2009), auraptene has been cited for its ability to delay breast cancer onset in a number of rodent models by disrupting Cyclin D function, a protein that enables cell division.…”

Citrus auraptene suppresses cyclin D1 and significantly delays N-methyl nitrosourea induced mammary carcinogenesis in female Sprague-Dawley rats

“…Coumarins are rapidly absorbed from the gastrointestinal tract and widely distributed [22]. Other coumarins like imperatorin, isoimperatorin and isopimpinellin have also been shown to be orally bioavailable [15,23,24,30]. Auraptene was detected in mammary glands, livers and tumors, suggesting that it is absorbed and distributed to the target organ.…”

“…Auraptene was detected in mammary glands, livers and tumors, suggesting that it is absorbed and distributed to the target organ. An article was recently published on the concentrations of auraptene in male Sprague-Dawley rats following oral administration [30]. From 1–4 h following gavage administration (500 μmol/kg bw, p.o.…”

“…From 1–4 h following gavage administration (500 μmol/kg bw, p.o. ), auraptene was found in high concentrations in stomach and intestine (up to ~2000 nmol/g stomach, 100 nmol/g small intestine, and 20 nmol/g large intestine) [30]. Hepatic concentrations of auraptene reached up to ~25 μm within 1–4 h of oral administration, then dropped rapidly [30].…”

Immunomodulatory effects of citrus fruit auraptene in vitro and in vivo

“…It has been suggested that detoxification and excretion of carcinogens are the most important function of auraptene for preventing carcinogenesis. Auraptene does not affect carcinogen-activated enzymes such as cytochrome P450s when it is orally administered to mice (Kleiner et al, 2008;Kuki, Hosotani, Ohigashi, & Murakami, 2008). However, auraptene accelerated the activation of metabolic and excretory enzymes such as glutathione S-transferase, suggesting that auraptene may suppress gene mutation by carcinogens in cells (Tanaka et al, 1997(Tanaka et al, , 1998.…”