Abstract
Dendrobine is the major active ingredient of Dendrobium nobile, Dendrobium chrysotoxum, and Dendrobium fimbriatum, all of which are used in traditional Chinese medicine owing
to their antitumor and anti-inflammation activities. Hence, investigation on
the interaction of dendrobine with cytochrome P450 enzymes could provide a reference
for the clinical application
of Dendrobium. The effects of dendrobine on cytochrome P450 enzymes activities were investigated
in the presence of 0, 2.5, 5, 10, 25, 50, and 100 µM dendrobine in pooled human liver
microsomes. The specific inhibitors were employed as the positive control and
the blank groups were set as the negative control. The Lineweaver-Burk plots were
plotted to characterize the
specific inhibition model and obtain the kinetic parameters. The study reveals
that dendrobine significantly inhibited the activity of CYP3A4, 2C19, and 2D6 with
IC50 values of
12.72, 10.84, and 15.47 µM, respectively. Moreover, the inhibition of CYP3A4
was found to be noncompetitive (Ki = 6.41 µM) and time dependent (KI = 2.541 µM−1,
Kinact
= 0.0452 min−1), while the inhibition of CYP2C19 and 2D6 was found to be competitive with the Ki values of 5.22 and 7.78 µM, respectively, and
showed no time-dependent trends. The in vitro inhibitory effect of dendrobine implies the potential drug-drug interaction between
dendrobine and CYP3A4-, 2C9-, and 2D6-metabolized
drugs. Nonetheless, these findings need further in vivo validation.
Key words
dendrobine -
Dendrobium nobile
-
Dendrobium chrysotoxum
-
Dendrobium fimbriatum
- CYP - metabolism - human liver microsomes - drug-drug interaction
