Abstract
Icariin is a flavonol glycoside isolated from Epimedium genus and has been used in the
treatment of sexual dysfunction and osteoporosis. Our laboratory has shown that icariin
is
beneficial in brain disorders and cardiovascular diseases. Since icariin is widely
used with
other herbs and drugs, to understand its potential herb-drug interactions is of importance.
Recently, icariin was shown to inhibit UDP-glucuronosyltransferases, particularly
the Ugt1
family enzymes in vitro, but little is known about such effects in vivo. This
study investigated the effects of icariin on the expression of UDP-glucuronosyltransferases
and
cytochrome P450 enzymes in the livers of mice. Adult mice were treated with icariin
at doses of
0, 40, 80, 160, and 320 mg/kg, p. o., for 7 days. Phenobarbital (120 mg/kg, p. o.)
and rifampin
(360 mg/kg, p. o.) were given twice daily for 3 days as positive controls. The livers
were
removed to determine UDP-glucuronosyltransferase activity and total RNA isolation.
The
UDP-glucuronosyltransferase activities towards 2-aminophenol were basically unaltered
by the
treatments. The expression of Cyp2b10 was increased 35-fold by phenobarbital, and
Cyp3a11 was
increased 4.5-fold by rifampin. Icariin did not affect Cyp2b10 and Cyp3a11 expression,
but
unexpectedly increased Cyp4a14 expression. Both phenobarbital and rifampin increased
Ugt1a1,
Ugt1a6, Ugt1a9, and icariin but did not show any suppressive effects on the Ugt1 family
genes.
Icariin at the highest dose (320 mg/kg) slightly increased Ugt2b1, Ugt2b5, and Ugt2b36.
These
findings indicate that icariin did not suppress UDP-glucuronosyltransferase expression,
instead,
it increased the mRNA of Cyp4a14 and slightly increased Ugt2b isoforms in mouse livers.
Key words
icariiin - phenobarbital - rifampin - cytochrome P450 - UDP-glucuronosyltransferase
