Modulatory effects of extracts of vinegar-baked Radix Bupleuri and saikosaponins on the activity of cytochrome P450 enzymes in vitro.
1. In this article, the modulatory effects of extracts from vinegar-baked Radix Bupleuri (VBRB) and saikosaponins on the activity of CYP1A2, CYP2C9 and CYP3A4 were investigated in vitro. 2. Microsomal in vitro incubation method was utilized to simulate metabolic reaction under physiological environment by incubating the marker with liver microsomes in the absence or presence of VBRB and saikosaponins. The contents of 4-acetamidophenol, 6β-hydroxyltestosterone and 4-hydroxydiclofenac, the metabolites of phenacetin, testosterone and diclofenac, which were selected as specific probe drugs of CYP1A2, CYP2C9 and CYP3A4, respectively, were analyzed by high-performance liquid chromatography. 3. The production of the metabolites was incubation time dependent. The modulatory effects of different VBRB extracts and saikosaponins on CYP isoforms increased with concentration. Among all the extracts studied, BC1 has a strong inhibition effect compared to the three CYP isoforms tested, while the others have only significant inhibition on the activity of CYP2C9. 4. This in vitro study demonstrated that various extracts of VBRB tested in this study have negligible potential to interfere with CYP1A2- and CYP3A4-metabolized drugs; risk of herb-drug interaction might occur when VBRB is concurrently taken with CYP2C9 substrates.
School of Pharmacy, Shenyang Pharmaceutical University , Shenyang , China and.
Tongya
T
Yu
Xianzhi
X
Chen
Yinjie
Y
Wang
Ruizhi
R
Zhao
Shirui
S
Mao
D019342:Acetic Acid / Q000737:chemistry; D000818:Animals; D029972:Bupleurum / Q000737:chemistry; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology; D041743:Herb-Drug Interactions; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D051379:Mice; D008862:Microsomes, Liver; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D012503:Saponins / Q000494:pharmacology*; D013997:Time Factors
C051274:Bupleurum root extract; D004365:Drugs, Chinese Herbal; D007527:Isoenzymes; D010936:Plant Extracts; D012503:Saponins; D009828:Oleanolic Acid; D003577:Cytochrome P-450 Enzyme System; D019342:Acetic Acid; C025759:saikosaponin D
Cytochrome P450 enzymes; modulate; saikosaponins; vinegar-baked Radix Bupleuri