Absorption, distribution and biliary excretion of cafestol, a potent cholesterol elevating compound in unfiltered coffees in mice

S.T.J. van Cruchten, D.R. de Waart, C. Kunne, G.J.E.J. Hooiveld, M.V. Boekschoten, M.B. Katan, R.P.J. Oude Elferink, R.F. Witkamp

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Scopus)

Abstract

Cafestol is a diterpene present in unfiltered coffees. It is the most potent cholesterol-elevating compound present in the human diet. However, the precise mechanisms underlying this effect are still unclear. In contrast, cafestol is also known as a hepatoprotective compound which is likely to be related to the induction of glutathione biosynthesis and conjugation. In the present study we investigated whole body distribution, biliary excretion and portal bioavailability of cafestol in mice. First, dissection was used to study distribution. Five hours after an oral dose with 3H labeled cafestol, most activity was found in small intestine, liver and bile. These results were confirmed by quantitative whole body autoradiography in a time course study which also showed elimination of all radioactivity within 48 hours after administration. Next, radiolabeled cafestol was dosed i.v. to bile duct cannulated mice. Five hours post dose 20% of the radioactivity was found in bile. Bile contained several metabolites but no parent compound. After intestinal administration of radioactive cafestol to portal vein cannulated mice, cafestol was shown to be rapidly absorbed into the portal vein as parent compound, a glucuronide and an unidentified metabolite. From the presence of a glucuronide in bile that can be deconjugated by a bacterial enzyme and the prolonged absorption of parent compound from the GI tract we hypothesize that cafestol undergoes enterohepatic cycling. Together with our earlier observation that epoxidation of the furan ring occurs in liver these findings merit further research on the process of accumulation of this coffee ingredient in liver and intestinal tract
Original languageEnglish
Pages (from-to)635-640
JournalDrug Metabolism and Disposition
Volume38
Issue number4
DOIs
Publication statusPublished - 2010

Fingerprint

Coffee
Cholesterol
Bile
Glucuronides
Portal Vein
Radioactivity
Liver
Hepatobiliary Elimination
cafestol
Diterpenes
Bile Ducts
Autoradiography
Biological Availability
Small Intestine
Glutathione
Gastrointestinal Tract
Dissection
Diet
Enzymes
Research

Keywords

  • chemopreventive components kahweol
  • raising factor
  • liver aminotransferases
  • diterpenes cafestol
  • serum-lipids
  • rat-liver
  • metabolism
  • 4-ipomeanol
  • enzymes
  • beans

Cite this

@article{f302a65a65ab4d75b2443e266592e5f2,
title = "Absorption, distribution and biliary excretion of cafestol, a potent cholesterol elevating compound in unfiltered coffees in mice",
abstract = "Cafestol is a diterpene present in unfiltered coffees. It is the most potent cholesterol-elevating compound present in the human diet. However, the precise mechanisms underlying this effect are still unclear. In contrast, cafestol is also known as a hepatoprotective compound which is likely to be related to the induction of glutathione biosynthesis and conjugation. In the present study we investigated whole body distribution, biliary excretion and portal bioavailability of cafestol in mice. First, dissection was used to study distribution. Five hours after an oral dose with 3H labeled cafestol, most activity was found in small intestine, liver and bile. These results were confirmed by quantitative whole body autoradiography in a time course study which also showed elimination of all radioactivity within 48 hours after administration. Next, radiolabeled cafestol was dosed i.v. to bile duct cannulated mice. Five hours post dose 20{\%} of the radioactivity was found in bile. Bile contained several metabolites but no parent compound. After intestinal administration of radioactive cafestol to portal vein cannulated mice, cafestol was shown to be rapidly absorbed into the portal vein as parent compound, a glucuronide and an unidentified metabolite. From the presence of a glucuronide in bile that can be deconjugated by a bacterial enzyme and the prolonged absorption of parent compound from the GI tract we hypothesize that cafestol undergoes enterohepatic cycling. Together with our earlier observation that epoxidation of the furan ring occurs in liver these findings merit further research on the process of accumulation of this coffee ingredient in liver and intestinal tract",
keywords = "chemopreventive components kahweol, raising factor, liver aminotransferases, diterpenes cafestol, serum-lipids, rat-liver, metabolism, 4-ipomeanol, enzymes, beans",
author = "{van Cruchten}, S.T.J. and {de Waart}, D.R. and C. Kunne and G.J.E.J. Hooiveld and M.V. Boekschoten and M.B. Katan and {Oude Elferink}, R.P.J. and R.F. Witkamp",
year = "2010",
doi = "10.1124/dmd.109.030213",
language = "English",
volume = "38",
pages = "635--640",
journal = "Drug Metabolism and Disposition",
issn = "0090-9556",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "4",

}

Absorption, distribution and biliary excretion of cafestol, a potent cholesterol elevating compound in unfiltered coffees in mice. / van Cruchten, S.T.J.; de Waart, D.R.; Kunne, C.; Hooiveld, G.J.E.J.; Boekschoten, M.V.; Katan, M.B.; Oude Elferink, R.P.J.; Witkamp, R.F.

In: Drug Metabolism and Disposition, Vol. 38, No. 4, 2010, p. 635-640.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Absorption, distribution and biliary excretion of cafestol, a potent cholesterol elevating compound in unfiltered coffees in mice

AU - van Cruchten, S.T.J.

AU - de Waart, D.R.

AU - Kunne, C.

AU - Hooiveld, G.J.E.J.

AU - Boekschoten, M.V.

AU - Katan, M.B.

AU - Oude Elferink, R.P.J.

AU - Witkamp, R.F.

PY - 2010

Y1 - 2010

N2 - Cafestol is a diterpene present in unfiltered coffees. It is the most potent cholesterol-elevating compound present in the human diet. However, the precise mechanisms underlying this effect are still unclear. In contrast, cafestol is also known as a hepatoprotective compound which is likely to be related to the induction of glutathione biosynthesis and conjugation. In the present study we investigated whole body distribution, biliary excretion and portal bioavailability of cafestol in mice. First, dissection was used to study distribution. Five hours after an oral dose with 3H labeled cafestol, most activity was found in small intestine, liver and bile. These results were confirmed by quantitative whole body autoradiography in a time course study which also showed elimination of all radioactivity within 48 hours after administration. Next, radiolabeled cafestol was dosed i.v. to bile duct cannulated mice. Five hours post dose 20% of the radioactivity was found in bile. Bile contained several metabolites but no parent compound. After intestinal administration of radioactive cafestol to portal vein cannulated mice, cafestol was shown to be rapidly absorbed into the portal vein as parent compound, a glucuronide and an unidentified metabolite. From the presence of a glucuronide in bile that can be deconjugated by a bacterial enzyme and the prolonged absorption of parent compound from the GI tract we hypothesize that cafestol undergoes enterohepatic cycling. Together with our earlier observation that epoxidation of the furan ring occurs in liver these findings merit further research on the process of accumulation of this coffee ingredient in liver and intestinal tract

AB - Cafestol is a diterpene present in unfiltered coffees. It is the most potent cholesterol-elevating compound present in the human diet. However, the precise mechanisms underlying this effect are still unclear. In contrast, cafestol is also known as a hepatoprotective compound which is likely to be related to the induction of glutathione biosynthesis and conjugation. In the present study we investigated whole body distribution, biliary excretion and portal bioavailability of cafestol in mice. First, dissection was used to study distribution. Five hours after an oral dose with 3H labeled cafestol, most activity was found in small intestine, liver and bile. These results were confirmed by quantitative whole body autoradiography in a time course study which also showed elimination of all radioactivity within 48 hours after administration. Next, radiolabeled cafestol was dosed i.v. to bile duct cannulated mice. Five hours post dose 20% of the radioactivity was found in bile. Bile contained several metabolites but no parent compound. After intestinal administration of radioactive cafestol to portal vein cannulated mice, cafestol was shown to be rapidly absorbed into the portal vein as parent compound, a glucuronide and an unidentified metabolite. From the presence of a glucuronide in bile that can be deconjugated by a bacterial enzyme and the prolonged absorption of parent compound from the GI tract we hypothesize that cafestol undergoes enterohepatic cycling. Together with our earlier observation that epoxidation of the furan ring occurs in liver these findings merit further research on the process of accumulation of this coffee ingredient in liver and intestinal tract

KW - chemopreventive components kahweol

KW - raising factor

KW - liver aminotransferases

KW - diterpenes cafestol

KW - serum-lipids

KW - rat-liver

KW - metabolism

KW - 4-ipomeanol

KW - enzymes

KW - beans

U2 - 10.1124/dmd.109.030213

DO - 10.1124/dmd.109.030213

M3 - Article

VL - 38

SP - 635

EP - 640

JO - Drug Metabolism and Disposition

JF - Drug Metabolism and Disposition

SN - 0090-9556

IS - 4

ER -