ARTICLE IN PRESS

Phytomedicine 13 (2006) 67–73

www.elsevier.de/phymed

CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants

T. Usiaa, H. Iwataa,b, A. Hiratsukac, T. Watabea, S. Kadotaa, Y. Tezukaa,d,
a
Institute of Natural Medicine, Toyama Medical and Pharmaceutical University, 2630-Sugitani, Toyama 930-0194, Japan
b
Kashima Laboratory, Mitsubishi Chemical Safety Institute Ltd., 14-Sunayama, Ibaraki 314-0255, Japan
c
Tokyo University of Pharmacy and Life Science, 1432-1-Horinouchi, Tokyo 192-0392, Japan
d
21st Century COE Program, Toyama Medical and Pharmaceutical University, 2630-Sugitani, Toyama 930-0194, Japan

Received 22 December 2003; accepted 6 June 2004

Abstract
Thirty samples of Indonesian medicinal plants were analyzed for their capacity to inhibit in vitro metabolism by
human cytochrome P450 3A4 (CYP3A4) and CYP2D6 with a radiometric assay. The MeOH-soluble fractions of 25
samples, prepared from water extracts, demonstrated inhibitory activity more than 50% on the metabolism mediated
by CYP3A4, and 21 samples on the metabolism mediated by CYP2D6. Among the MeOH-soluble fractions, Piper
nigrum leaf showed the highest inhibitory activity against CYP3A4 (91.7%), and Punica granatum against CYP2D6
(98.1%). The water extracts of which MeOH-soluble fraction showed inhibitory activity more than 70% were
fractionated with EtOAc. From the EtOAc-soluble fractions, Curcuma heyneana (67.0%), Pi. cubeba (75.0%), Pi.
nigrum fruit (84.0%), Pi. nigrum leaf (85.8%), and Zingiber aromaticum (75.3%) demonstrated inhibitory activity more
than 50% on the metabolism mediated by CYP3A4, but only Pi. nigrum fruit (72.8%) and Pi. nigrum leaf (69.1%)
showed strong inhibitory activity against CYP2D6. For samples that showed more than 70% inhibition, their IC50
values were determined. The most potent inhibitory activity against CYP3A4 (IC50 value of 25 mg/ml) was found for
the extract of Pi. nigrum leaf, while that of Catharanthus roseus showed the most potent inhibitory effect against
CYP2D6 (IC50 value of 11 mg/ml). These results should indicate once more the possibility of potential medicinal
plant–drug interactions.
r 2005 Elsevier GmbH. All rights reserved.

Keywords: Cytochrome P450; Jamu; Drug interaction; Inhibition; CYP3A4; CYP2D6

Introduction drugs such as cyclosporine A, dihydropyridines, ethiny-

Cytochrome P450 (CYP) is the main enzyme which
catalyzes the metabolism of drugs and other xenobiotics.
CYP3A4, the major hepatic and intestinal CYP in
humans, metabolizes more than 50% of clinically used
Corresponding author. Institute of Natural Medicine, Toyama
Medical and Pharmaceutical University, 2630-Sugitani, Toyama
930-0194, Japan Tel.: 81 76 434 7627; fax: 81 76 434 5059.
E-mail address: tezuka@ms.toyama-mpu.ac.jp (Y. Tezuka).
lestradiol, midazolam, terfenadine, and triazolam (Ren-
dic and DiCarlo, 1997). CYP2D6 catalyzes the
metabolism of about 30% of all drugs including
amitriptyline, imipramine, haloperidol, propranolol,
and dextromethorphan (Clarke and Jones, 2002).
Recently, several reports have demonstrated that
natural compounds and herbal products may cause
pharmacokinetic interaction with western drugs used
clinically when they are simultaneously administrated
(Foster et al., 1999; Nebel et al., 1999; Taylor and Wilt,

0944-7113/$ - see front matter r 2005 Elsevier GmbH. All rights reserved.
doi:10.1016/j.phymed.2004.06.022
 ARTICLE IN PRESS
68 T. Usia et al. / Phytomedicine 13 (2006) 67–73
1999). The use of medicinal herbs has particularly
increased over the past few years among specific patient
populations including HIV-infected patients. St. John’s
wort altered pharmacokinetics of the HIV protease
inhibitor, indinavir in individuals on retroviral therapy
(Piscitelli et al., 2000). Indeed, plasma concentrations of
the HIV protease inhibitor, saquinavir, have been
decreased in individuals exposed long-term to garlic
supplements (Piscitelli et al., 2002). The increased
clearance of saquinavir may be due to induction of
hepatic and/or intestinal CYP3A4. The most widely
studied natural product is grapefruit juice, which has
been found to increase the bioavailability and/or to
prolong the metabolic elimination of many drugs such
as dihydropyridine-type calcium channel blockers,
histamine-1 receptor antagonists (e.g., terfenadine),
quinidine, benzodiazepines (e.g., midazolam), 17b-estra-
diol, and caffeine (Ameer and Weintraub, 1997; Bailey
et al., 1998).
Indonesia, a country in Southeast Asia, has many
medicinal plants which are used as traditional medicines
‘‘Jamu’’ (Sastroamidjojo, 1997). Those medicinal plants
have been used from the ancient time to now, and are
largely consumed by people of different levels in villages
and also in big cities. People could easily buy ready-
made ‘‘Jamu’’ which is packed in the form of powder,
pills, capsules, drinking liquid, and ointment. There are
still ‘‘Jamu’’ shops to sell only ingredients or to prepare
the ‘‘Jamu’’ on spot by request. It is a common view
across the country that some women are roaming the
street to sell ‘‘Jamu’’, and many Indonesians start their
day with drinking ‘‘Jamu’’. These traditional medicines
are almost unregulated, and many patients do not
inform their physician about the traditional medicines
they consume. Therefore, interactions between tradi-
tional medicines and drugs prescribed clinically are
becoming a concern. To the best of our knowledge,
there have been no reports on the inhibitory potential of
Indonesian medicinal plants against CYP. Thus, we
chose 30 medicinal plants which are generally used in
Indonesian traditional medicines (Sastroamidjojo, 1997;
PT Eisai Indonesia, 1995) (Table 1) and evaluated their
inhibitory activity against CYP3A4 and CYP2D6.
Materials and methods
Medicinal plants
Indonesian medicinal plants were obtained at GORO
traditional market, Jakarta, Indonesia, in May 2002 and
voucher samples are preserved at the Museum of
Materia Medica, Research Center for Ethnomedicines,
Institute of Natural Medicine, Toyama Medical and
Pharmaceutical University, Toyama, Japan (Table 1).
Extraction and preparation of test solutions
Each medicinal plant (25–150 g) was cut into small
pieces and extracted with water (150–400 ml, reflux,
2 h,  2). The water solution was concentrated under
reduced pressure and lyophilized to give a water extract.
A part of the water extract (0.5 g) from each medicinal
plant was extracted with MeOH (15 ml), followed by
centrifugation to facilitate removal of the supernatant,
to give a MeOH-soluble fraction. The MeOH-soluble
fraction was evaporated and redissolved in 1.5 ml of
MeOH and used as a test solution. The medicinal plants
on which the MeOH-soluble fraction showed strong
inhibition against CYP3A4 and/or CYP2D6, an EtOAc-
soluble fraction was prepared from the water extract by
extracting with EtOAc (15 ml), followed by centrifuga-
tion. The EtOAc-soluble fraction was evaporated and
dissolved in 1.5 ml of MeOH and used as a test solution.
Chemicals
Quinidine sulfate dihydrate and ketoconazole were
obtained from Wako Pure Chemicals Industry, Ltd.
(Osaka, Japan). [N-methyl-14C]Erythromycin (55 mCi/
mmol, 499% pure) and [O-methyl-14C]dextromethor-
phan (55 mCi/mmol, 499% pure) were purchased from
American Radiolabeled Chemicals, Inc. (St. Louis, MO,
USA). Human liver microsomes (HLM) were obtained
from Xenotech, LLC (Kansas, KS, USA) and stored at
80 1C prior to use. b-Nicotinamide adenine dinucleo-
tide phosphate (NADP+, oxidized form), glucose-6-
phosphate (G-6-P), and G-6-P dehydrogenase were
purchased from Oriental Yeast Co., Ltd. (Tokyo,
Japan). All other chemicals and solvents were of the
highest grade available.
CYP inhibitory activity
Inhibitory activity against CYP3A4 was assayed by
the method of Riley and Howbrook (1998) with a slight
modification. Briefly, the assay was performed in a
disposable culture tube of 13  100 mm (Iwaki, Tokyo,
Japan). Tubes were designated as ‘‘control’’, ‘‘positive
control’’, and ‘‘test’’. The control tube consisted of 2.5 ml
of MeOH; positive control consisted of 2.5 ml of
ketoconazole (100 mM); and test tubes consisted of
2.5 ml of samples (equivalent to 1.65 mg/ml of extract).
To all tubes were added 150 ml of phosphate buffer (pH
7.4), 197.5 ml of ultrapure water, 50 ml of [N-methyl-14-
C]erythromycin (0.1 mCi/incubation, 1 mM in 5% of
MeOH), and 50 ml of HLM (4 mg/ml). The total
incubation volume was 500 ml. After 5 min preincuba-
tion under shaking at 37 1C, the reaction was initiated by
addition of 50 ml of NADPH-generating system
(4.20 mg/ml of NADP+, 100 mM of G-6-P, 100 mM of
Table 1. Indonesian medicinal plants, their families, parts used, local names, therapeutic applications, and voucher specimen numbers

Plant name Family Part used Local name Therapeutic application TMPW No.

Alpinia galanga (L.) SWARTZ Zingiberaceae Rhizome Laos Stomachic, anorexia 22261
Alstonia scholaris (L.) R.BR. Apocynaceae Bark Pulai Fever, anorexia, nephritis, diabetes, malaria, 22262
hypertension
Alstonia scholaris (L.) R.BR. Apocynaceae Leaf Pulai Beri-beri, syphilis, diabetes 22263
Alyxia reinwardtii BL. Apocynaceae Bark Pulosari Fever, gastritis, albuminuria, whooping cough, 22264
carminative, leucorrhea, gonorrhea, menstrual disorder
Amomum compactum SOLAND ex Zingiberaceae Fruit Kapulaga Cough, tonsillitis, menstrual disorder, colic, influenza, 22265
MATON gastritis
Amomum compactum SOLAND ex Zingiberaceae Rhizome Kapulaga Tonic, fever 22266
MATON
Andrographis paniculata (BURM. Acanthaceae Aerial part Sambiloto Diabetes, gonorrhea, syphilis, tonsillitis, epilepsy, 22267
F.) NEES diphtheria, fever, typhus, tonic
Catharanthus roseus (L.) G. DON Apocynaceae Aerial part Tapak dara Diabetes, cancer, malaria, hypertension 22268
Cinnamomum burmani NEES ex Lauraceae Bark Kayu manis Diarrhea, malaria 22269
BL.
Curcuma aeruginosa ROXB. Zingiberaceae Rhizome Temu ireng Anthelmintic, obesity, scabies, rheumatism 22270
Curcuma heyneana VAL & V. ZIJP Zingiberaceae Rhizome Temu giring Anthelmintic 22271
Curcuma xanthorrhiza ROXB. Zingiberaceae Rhizome Temu lawak Anticonvulsant, hemorrhoid, malaria, diarrhea, 22272
anorexia, gastritis, anemia, jaundice
Cymbopogon nardus (L.) RENDLE Gramineae Aerial part Sere Diaphoretic, body warming 22273
Foeniculum vulgare MILL. Umbelliferae Seed Adhas Albuminuria, insomnia, menstrual disorder 22274
Glycyrrhiza glabra L. Leguminosae Stem Kayu legi Hepatitis, tonic 22275
Melaleuca leucadendron L. Myrtaceae Leaf Kayu putih Vertigo, anticonvulsant, tooth-ache, rheumatism 22276
Piper cubeba L. Piperaceae Fruit Kemukus Dysentery, gonorrhea 22277
Piper nigrum L. Piperaceae Fruit Marica putih Carminative, hypertension, dyspnea 22278
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Piper nigrum L. Piperaceae Leaf Marica putih Tooth-ache 22279

Punica granatum L. Punicaceae Fruit Delima putih Leucorrhea, constipation, diarrhea, dysentery 22280
T. Usia et al. / Phytomedicine 13 (2006) 67–73

Rheum palmatum L. Polygonaceae Root Klembak Tonic, stomach-ache 22281

Santalum album L. Santalaceae Wood Kayu cendana Dysentery, asthma, fever, gonorrhea 22282
Sericocalyx crispus (L.) BREMEK Acanthaceae Leaf Keji beling Diabetes, renal calculus, vesical calculus 22283
Strychnos ligustrina BL. Loganiaceae Leaf Bidara laut Antidote, depurative, stomachic 22284
Strychnos ligustrina BL. Loganiaceae Wood Bidara laut Anthelmintic, boil, chancre, depurative, antidote for 22285
snake poisoning
Syzygium aromaticum (L.) Myrtaceae Flower Cengkeh Cold, cough 22286
MERR. & PERRY
Tamarindus indica L. Leguminosae Fruit Asem Fever, laxative 22287
Tinospora crispa (L.) DIELS Menispermaceae Stem Brotowali Fever, diuretic, tonic, diabetes 22288
Zingiber aromaticum VAL Zingiberaceae Rhizome Lempuyang wangi Cholescystopathy, whooping cough, jaundice, arthritis, 22289
anorexia, cold, cholera, anemia, malaria, rheumatism,
abdominalgia
Zingiber cassumunar ROXB. Zingiberaceae Rhizome Bengle Obesity, vertigo, constipation, cold, jaundice, 22290
anticonvulsant, rheumatism
69
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70 T. Usia et al. / Phytomedicine 13 (2006) 67–73

MgCl2, and 10 U/ml of G-6-P dehydrogenase) and Results and discussion

continued for 10 min under the same conditions. The
reaction was stopped by the addition of 125 ml of 10%
trichloroacetic acid (Nacalai tesque, Inc., Kyoto,
Japan). After centrifugation at 3000 rpm for 10 min at
room temperature, the supernatant was applied to Envi-
Carb solid-phase extraction column (Supelco, PA, UK)
and was eluted by ultrapure water (500 ml  2). After
addition of 10 ml of Clear-sol I (Nacalai tesque, Inc.),
the eluted radioactivity was quantified by liquid
scintillation counting LS 6500 (Beckman, CA, USA).
Correction was made for radioactivity eluted from the
control in which HLM and NADPH-generating system
were omitted. The assays were performed in duplicate
for all samples. The inhibitory activity against CYP2D6
was also measured by the method of Rodrigues (1996)
with a slight modification. The assay was done with
the same procedure in the case of CYP3A4 using
[O-methyl-14C]dextromethorphan (0.1 mCi/incubation,
100 mM in 5% of MeOH) as a substrate and longer
incubation time (20 min). Quinidine (100 mM) was used
as a positive control.
To calculate the IC50 values (concentrations of sample
causing 50% reduction in activity relative to the control)
of the sample that showed more than inhibition 70%,
the sample was added to the reaction mixture at a
concentration range of 0–1.65 mg/ml. The relationship
between the concentration of sample and the remaining
activity was analyzed using software product WinNon-
lin Ver.3.1 (Pharsight Corp., Mountain View, CA,
USA). IC50 values were calculated by linear regression
analysis of the sample concentration versus percentage
control activity plots.
All 30 samples of Indonesian medicinal plants were
analyzed for their ability to inhibit CYP3A4-mediated
metabolism of [N-methyl-14C]erythromycin and
CYP2D6-mediated metabolism of [O-methyl-14C]-dex-
tromethorphan. The amount of the test solution used
was 1.65 mg/ml of extract according to Iwata et al.
(2004), or equivalent to 2–10 mg of herbal powder which
is 30 times smaller than the minimal amount of one time
consumption of Indonesian traditional medicine, gen-
erally. The MeOH-soluble fractions of 14 samples
(Alyxia reinwardtii, Andrographis paniculata, Curcuma
heyneana, Cymbopogon nardus, Glycyrrhiza glabra, Piper
cubeba, Pi. nigrum fruit, Pi. nigrum leaf, Pu. granatum,
Rheum palmatum, Sanatalum album, Syzygium aromati-
cum, Tinospora crispa, and Zingiber aromaticum)
showed inhibitory activity over 70% on the metabolism
mediated by CYP3A4, and Pi. nigrum leaf revealed the
strongest activity (91.7%) (Fig. 1). Twelve samples
(Alpinia galanga, Alstonia scholaris bark, Amomum
compactum fruit, Am. compactum rhizome, Ca. roseus,
Cinnamomum burmani, Cu. aeruginosa, Cu. xanthorrhi-
za, Melaleuca leucodendron, Strychnos ligustrina leaf, St.
ligustrina wood, and Z. cassumunar) showed inhibition
between 30% and 70%. Other samples showed inhibi-
tion only less than 30%.
On the metabolism mediated by CYP2D6, 15 samples
(Als. scholaris bark, An. paniculata, Ca. roseus, Ci.
burmani, G. glabra, Pi. nigrum fruit, Pi. nigrum leaf, Pu.
granatum, R. palmatum, Sa. album, St. ligustrina leaf, St.
ligustrina wood, Sy. aromaticum, Ti. crispa, and Z.
aromaticum) demonstrated inhibitory activity over 70%

100

90

80

70
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Fig. 1. Inhibitory effect of MeOH-soluble fractions of Indonesian medicinal plants (1.65 mg/ml of water extract powder) on
CYP3A4-mediated metabolism of [N-methyl-14C]erythromycin (’), and on CYP2D6-mediated metabolism of [O-methyl-14C]dex-
tromethorphan (&). Ketoconazole and quinidine (1 mM) were used as the positive control for CYP3A4 and CYP2D6, respectively.
 ARTICLE IN PRESS
T. Usia et al. / Phytomedicine 13 (2006) 67–73 71

100

90
80

70

% Inhbition 60

50
40

30
20

10

0
)

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)
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bu ria t)

f)

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St igu (w )

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ar
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. p atu (lea

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u m oo
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id

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t
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us ia

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Fig. 2. Inhibitory effect of EtOAc-soluble fractions of Indonesian medicinal plants (1.65 mg/ml of water extract powder) on
CYP3A4-mediated metabolism of [N-methyl-14C]erythromycin (’), and on CYP2D6-mediated metabolism of [O-methyl-14C]dex-
tromethorphan (&). Ketoconazole and quinidine (1 mM) were used as the positive control for CYP3A4 and CYP2D6, respectively.

and 7 of them were more than 90%: An. paniculata
(92.6%), Ca. roseus (96.4%), G. glabra (94.5%), Pi.
nigrum leaf (90.9%), Pu. granatum (98.1%), R. palma-
tum (96.4%), and Sy. aromaticum (94.5%) (Fig. 1). The
inhibitory activity more than 30% but less than 70%
was found with Aly. reinwardtii, Am. compactum
rhizome, Cu. aeruginosa, Cu. heyneana, Cu. xanthor-
rhiza, Cy. nardus, M. leucodendron, and Pi. cubeba. The
remaining samples showed inhibition only less than
30%.
Then, the EtOAc-soluble fraction was prepared from
the water extract whose MeOH-soluble fraction showed
inhibition more than 70%. Among 19 EtOAc-soluble
fractions, those of Pi. cubeba (75.0%), Pi. nigrum fruit
(84.0%), Pi. nigrum leaf (85.8%), and Z. aromaticum
(75.3%) demonstrated inhibitory activity over 70% on
the metabolism mediated by CYP3A4 (Fig. 2). An.
paniculata, Cu. heyneana, and Sy. aromaticum showed
the inhibitory activity between 30% and 70%. Other
samples showed inhibition only less than 30% against
CYP3A4. On the other hand, only Pi. nigrum fruit
(72.8%) demonstrated inhibitory activity over 70% on
the metabolism mediated by CYP2D6 (Fig. 2), and the
inhibition between 30% and 70% was found on Pi.
nigrum leaf (69.1%).
The IC50 values of the samples that showed inhibition
more than 70% are listed in Table 2. All samples showed
inhibitory activity on the metabolism mediated by
CYP3A4 and CYP2D6 in a concentration-dependent
manner. The potent inhibitory activity against CYP3A4
with IC50 values less than 100 mg/ml were found on Pi.
cubeba (53 mg/ml), Pi. nigrum fruit (29 mg/ml), Pi. nigrum
leaf (25 mg/ml), and Pu. granatum (35 mg/ml), while Ca.
roseus was the most potent inhibitory activity against
CYP2D6 with an IC50 value of 11 mg/ml.
These experiments have demonstrated that 63% of
the selected samples of Indonesian medicinal plants
significantly inhibited CYP3A4-mediated metabolism of
[N-methyl-14C]erythromycin and CYP2D6-mediated
metabolism of [O-methyl-14C]-dextromethorphan. Tsu-
kamoto et al. (2002) reported five bisalkaloids, dipiper-
amides A–E, and a lignan, ( )-hinokinin, as potent
CYP3A4 inhibitors of Pi. nigrum. In addition, ( )-
hinokinin with two methylenedioxyphenyl groups in the
molecule was also isolated from Pi. cubeba (Parmar et
al., 1997). Methylenedioxyphenyl compounds were well
known to inhibit CYP reaction through the formation
of stable complexes with CYP enzymes (Marcus et al.,
1985). Thus, the inhibitory activity of Pi. cubeba may be
due to constituents like ( )-hinokinin. Surprisingly, Pi.
nigrum also showed strong inhibition against CYP2D6
(470%), suggesting the presence of other inhibitor(s).
The dried roots of G. glabra have been consumed for the
past 6000 years and are used as flavoring and sweating
agents, demulcents, and expectorants in the Western
world and as antiallergic and anti-inflammatory agents
in Japan and China (Chandler, 1985; Mitschner et al.,
1986). Licorice root extract, as well as its major
isoflavan glabridin, is a potent antioxidant against
LDL oxidation in mice and humans (Rosenblat et al.,
1999), and Kent et al. (2002) reported that glabridin
inactivates CYP3A4 in a time-, concentration-, and
NADPH-dependent manner; i.e., mechanism-based in-
activation. On the other hand, 2,4-dimethylglabridin did
not show the inhibition on CYP3A4. Thus, the two
hydroxyl groups on the 2 and 4 positions of the B ring
 ARTICLE IN PRESS
72 T. Usia et al. / Phytomedicine 13 (2006) 67–73

Table 2. IC50 values of the Indonesian medicinal plants on between Indonesian medicinal plants and concomitantly
the metabolism mediated by CYP3A4 and CYP2D6 administrated conventional drugs. Further studies on
these plants, including the identification of the active
Plant name IC50 value (mg/ml)
constituents and in in vivo system, are under progress
CYP3A4 CYP2D6 and will be reported elsewhere.

MeOH-soluble fraction
Als. scholaris bark NT 222
Aly. reinwardtii 447 NT Acknowledgements
An. paniculata 102 86
Ca. roseus NT 11 A part of this work was supported by a Grant-in-Aid
Ci. burmani NT 1203 for the 21st Century COE Program from the Ministry of
Cu. heyneana 271 NT Education, Culture, Sports, Science and Technology,
Cy. nardus 370 NT Japan.
G. glabra 345 515
Pi. cubeba 53 NT
Pi. nigrum fruit 29 315
Pi. nigrum leaf 25 146 References
Pu. granatum 35 32
R. palmatum 467 385 Ameer, B., Weintraub, R.A., 1997. Drug interactions with
Sa. album 337 886 grapefruit juice. Clin. Pharmacokinet. 33, 103–121.
St. ligustrina leaf NT 302 Bailey, D.G., Malcolm, J., Arnold, O., Spence, J.D., 1998.
St. ligustrina wood NT 637 Grapefruit juice–drug interactions. Br. J. Clin. Pharmacol.
Sy. aromaticum 219 249 46, 101–110.
Ti. crispa 428 488 Chandler, R.F., 1985. Licorice, more than just a flavour. Can.
Z. aromaticum 102 693 Pharm. J. 118, 421–424.
Clarke, S.E., Jones, B.C., 2002. Human cytochromes P450 and
EtOAc-soluble fraction their role in metabolism-based drug–drug interactions. In:
Pi. cubeba 332 NT Rodrigues, A.D. (Ed.), Drug–Drug Interactions. Marcel
Pi. nigrum fruit 223 344 Dekker, New York, pp. 55–88.
Pi. nigrum leaf 240 NT Foster, B.C., Vandenhoek, S., Hanna, J., Akhtar, M.H.,
Z. aromaticum 376 NT Krantis, A., 1999. Effect of natural health products on
cytochrome P-450 drug metabolism. Can. J. Infect. Dis.
NT – not tested.
Suppl. 10 (B), 18.
Hasegawa, A., Yoshino, M., Nakamura, H., Ishii, I.,
Watanabe, T., Kiuchi, M., Ishikawa, T., Ohmori, S.,
should be important for the CYP3A4 inactivation. In Kitada, M., 2002. Identification of inhibitory component
our experiment, G. glabra also showed inhibitory in cinnamon O-methoxycinnamaldehyde inhibits CYP1A2
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