METABOLISM OF HONOKIOL IN RAT AND HUMAN LIVER
3515
Analogously, human recombinant SULT isoforms
were screened for honokiol sulfation. We found that
several of these isoenzymes are responsible for the
conjugation of honokiol with sulfuronic acid. Although
SULTs 1A1 1, 1A1 2, and 1A2 demonstrated far
higher sulfation rates in vitro at 5 and 40 :M, in vivo
only SULTs 1A3, 1B1, and 1E1 may contribute sig-
nificantly to honokiol sulfation based on very low Km
values (0.41–1.07 :M).
CONCLUSION
Our data demonstrated that honokiol is extensively
metabolized in rat and human liver. Glucuronidation
and sulfation will therefore play a key role in the
elimination of dietary honokiol in humans after oral
uptake. Measurements of both parent compound and
metabolites will be necessary to correlate pharma-
cokinetic with pharmacological activity.
∗
∗
As demonstrated for glucuronidation, we could also
show hepatic as well as extrahepatic sulfation of hon-
okiol. SULT1A1 levels are very high in the liver and
ACKNOWLEDGMENTS
This study was supported by grants of the
2
6
is also present at lower levels in many other tissues,
¨
Jubil a¨ umsfonds der Osterreichischen Nationalbank
whereas lower mRNA levels have been found for
SULT1A2 than for other SULT1A members in the
liver, kidney, brain, ovary, and some other sections
of the gastrointestinal tract. As recently published
data also show the expression of SULT1A2 protein in
Caco-2 cells as well as in individual samples of the
liver and caecum,27,28 our study is indicative of the
physiological role of SULT1A2 in honokiol biotrans-
formation. SULT1A3 expression is extremely high in
the gut, detectable in many other extrahepatic tis-
(
12600) and Fonds zur wissenschaftlichen Forschung
(
FWF) (P21083-B11) to W. J a¨ ger.
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DOI 10.1002/jps
JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 100, NO. 8, AUGUST 2011