Effects of phillyrin and forsythoside A on rat cytochrome P450 activities in vivo and in vitro.
1. Phillyrin and forsythoside A are two important active ingredients in Forsythia suspensa. However, the effects of phillyrin and forsythoside A on the activities of cytochrome P450 (CYP450) remain unclear. 2. This study aimed to investigate the effects of phillyrin and forsythoside A on the activities of CYP1A2, CYP2C11, CYP2D1 and CYP3A1/2 by cocktail probe drugs in rats both in vivo and in vitro. 3. Many pharmacokinetic parameters of caffeine and metoprolol in phillyrin pretreatment group, caffeine and tolbutamide in forsythoside A pretreatment group were affected significantly. In rat liver microsomal incubation system, the concentrations of acetaminophen and dextrophan in the phillyrin pretreatment group are higher than blank control group by 207.69% and 125.00%, however, the concentrations of 4-hydroxytolbutamide and 6β-hydroxytestosterone were not significantly altered. The concentrations of acetaminophen and 4-hydroxytolbutamide in the forsythoside A pretreatment group are higher than blank control group by 223.07% and 154.16%, whereas the concentrations of dextrophan and 6β-hydroxytestosterone were not significantly altered. 4. These results indicated that Phillyrin had potential inductive effects on rat CYP1A2 and CYP2D1 activities, without affecting CYP2C11 and CYP3A1/2 activities. Moreover, forsythoside A had inductive effects on the activities of CYP1A2 and CYP2C11, without affecting CYP2D1 and CYP3A1/2 activities.
a Department of Pharmacy , The Second Affiliated Hospital, Harbin Medical University , Harbin , China , and.
Yanwen
Y
Cheng
a Department of Pharmacy , The Second Affiliated Hospital, Harbin Medical University , Harbin , China , and.
Xiaoling
X
Liang
a Department of Pharmacy , The Second Affiliated Hospital, Harbin Medical University , Harbin , China , and.
Liying
L
Feng
b Department of Pharmacy , The Third Affiliated Hospital, Harbin Medical University , Harbin , China.
Duo
D
Liu
a Department of Pharmacy , The Second Affiliated Hospital, Harbin Medical University , Harbin , China , and.
Mengnan
M
Qin
a Department of Pharmacy , The Second Affiliated Hospital, Harbin Medical University , Harbin , China , and.
Shuang
S
Liu
a Department of Pharmacy , The Second Affiliated Hospital, Harbin Medical University , Harbin , China , and.
Gaofeng
G
Liu
b Department of Pharmacy , The Third Affiliated Hospital, Harbin Medical University , Harbin , China.
Mei
M
Dong
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005960:Glucosides / Q000633:toxicity*; D006027:Glycosides / Q000633:toxicity*; D008297:Male; D051381:Rats
D005960:Glucosides; D006027:Glycosides; D003577:Cytochrome P-450 Enzyme System; C058049:forsythiaside; C075528:phillyrin
CYP1A2; CYP2C11; CYP2D1; CYP3A1/2; cytochrome P450; forsythoside A; phillyrin