Effects of Angelicae tenuissima radix, Angelicae dahuricae radix and Scutellariae radix extracts on cytochrome P450 activities in healthy volunteers.
Three kinds of herbal medicines, commonly used in Korea, Angelicae tenuissima radix, Angelicae dahuricae radix and Scutellariae radix were studied to evaluate their effect on cytochrome P450 (CYP) activities in healthy volunteers. A total of 24 healthy male volunteers were assigned to one of three parallel herbal treatment groups, each consisting of eight volunteers. A cocktail of probe drugs for CYP enzymes was orally administered before and after multiple administrations of herbal medicines, three times a day for 13 days. Probe drugs used to measure CYP activities were caffeine (CYP1A2), losartan (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), chlorzoxazone (CYP2E1) and midazolam (CYP3A4). The probe drugs and their metabolites were quantified in plasma or urine using HPLC or LC-MS/MS. Changes in each CYP activity was evaluated by metabolic ratio of the probe drug (concentration ratio of metabolite to parent form at reference time point) following the herbal medication period, compared to the baseline values. A. dahuricae radix significantly decreased CYP1A2 activity to 10% of baseline activity (95% CI: 0.05-0.21). S. radix also showed significant changes in CYP2C9 and CYP2E1 activities. Compared to baseline values, the metabolic activities of losartan were decreased to 71% (0.54-0.94). In addition, S. radix showed a 1.42-fold (1.03-1.97) increase in chlorzoxazone metabolic activity. However, CYP activities were not meaningfully influenced by A. tenuissima radix. Changes in certain CYP activities were observed after the administration of S. radix and A. dahuricae radix in healthy volunteers. Therefore, herbal medicines containing S. radix or A. dahuricae radix are candidates for further evaluation of clinically significant CYP-mediated herb-drug interactions in human beings.
Yi
SoJeong
S
Department of Pharmacology and Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, South Korea.
Cho
Joo-Youn
JY
Lim
Kyoung Soo
KS
Kim
Kyu-pyo
KP
Kim
Jaewoo
J
Kim
Bo-Hyung
BH
Hong
Jang-hee
JH
Jang
In-Jin
IJ
Shin
Sang-Goo
SG
Yu
Kyung-Sang
KS
D000328:Adult; D029969:Angelica / Q000737:chemistry*; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D002110:Caffeine / Q000494:pharmacology; D002753:Chlorzoxazone / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D003915:Dextromethorphan / Q000494:pharmacology; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D041743:Herb-Drug Interactions; D006801:Humans; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008874:Midazolam / Q000494:pharmacology; D009853:Omeprazole / Q000494:pharmacology; D008517:Phytotherapy; D056910:Republic of Korea; D031364:Scutellaria baicalensis / Q000737:chemistry*; D053719:Tandem Mass Spectrometry; D055815:Young Adult
D004365:Drugs, Chinese Herbal; D002110:Caffeine; D003915:Dextromethorphan; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D019392:Cytochrome P-450 CYP2E1; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D019388:Cytochrome P-450 CYP1A2; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D002753:Chlorzoxazone; D019808:Losartan; D009853:Omeprazole; D008874:Midazolam