Inhibition of cytochrome P450 3A4 activity by schisandrol A and gomisin A isolated from Fructus Schisandrae chinensis

C. K. Wan; Anfernee K W Tse; Zhiling Yu; G. Y. Zhu; H. Wang; David W F Fong

doi:10.1016/j.phymed.2009.12.005

Inhibition of cytochrome P450 3A4 activity by schisandrol A and gomisin A isolated from Fructus Schisandrae chinensis

C. K. Wan, Anfernee K W Tse, Zhiling Yu, G. Y. Zhu, H. Wang, David W F Fong^*

^*Corresponding author for this work

Research output: Contribution to journal › Journal article › peer-review

34 Citations (Scopus)

Abstract

We studied the effects of schisandrol A (SCH) and gomisin A (GOM), two of the main bioactive components of Fructus Schisandrae chinensis, on cytochrome P450-3A4 (CYP3A4) activity and cellular glutathione (GSH) level. In a cell-free system both SCH and GOM inhibited CYP3A4 activity with IC₅₀ values of 32.02 μM and 1.39 μM, respectively. SCH or GOM at concentrations up to 100 μM did not alter cellular GSH level in regular HepG2 cells and P-glycoprotein overexpressing HepG2-DR cells. Since SCH and GOM may reverse multidrug resistance (MDR) by impeding the activity of P-glycoprotein, a membrane xenobiotic exporter, SCH or GOM could affect cellular drug metabolism in addition to drug uptake.

Original language	English
Pages (from-to)	702-705
Number of pages	4
Journal	Phytomedicine
Volume	17
Issue number	8-9
DOIs	https://doi.org/10.1016/j.phymed.2009.12.005
Publication status	Published - Jul 2010

Scopus Subject Areas

Molecular Medicine
Pharmacology
Pharmaceutical Science
Drug Discovery
Complementary and alternative medicine

User-Defined Keywords

Cytochrome P450 3A4
Glutathione
Gomisin A
Multidrug resistance
Schisandra chinensis
Schisandrol A

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10.1016/j.phymed.2009.12.005

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@article{00995783bb99488aa811651a729b6727,

title = "Inhibition of cytochrome P450 3A4 activity by schisandrol A and gomisin A isolated from Fructus Schisandrae chinensis",

abstract = "We studied the effects of schisandrol A (SCH) and gomisin A (GOM), two of the main bioactive components of Fructus Schisandrae chinensis, on cytochrome P450-3A4 (CYP3A4) activity and cellular glutathione (GSH) level. In a cell-free system both SCH and GOM inhibited CYP3A4 activity with IC50 values of 32.02 μM and 1.39 μM, respectively. SCH or GOM at concentrations up to 100 μM did not alter cellular GSH level in regular HepG2 cells and P-glycoprotein overexpressing HepG2-DR cells. Since SCH and GOM may reverse multidrug resistance (MDR) by impeding the activity of P-glycoprotein, a membrane xenobiotic exporter, SCH or GOM could affect cellular drug metabolism in addition to drug uptake.",

keywords = "Cytochrome P450 3A4, Glutathione, Gomisin A, Multidrug resistance, Schisandra chinensis, Schisandrol A",

author = "Wan, {C. K.} and Tse, {Anfernee K W} and Zhiling Yu and Zhu, {G. Y.} and H. Wang and Fong, {David W F}",

year = "2010",

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doi = "10.1016/j.phymed.2009.12.005",

language = "English",

volume = "17",

pages = "702--705",

journal = "Phytomedicine",

issn = "0944-7113",

publisher = "Elsevier",

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TY - JOUR

T1 - Inhibition of cytochrome P450 3A4 activity by schisandrol A and gomisin A isolated from Fructus Schisandrae chinensis

AU - Wan, C. K.

AU - Tse, Anfernee K W

AU - Yu, Zhiling

AU - Zhu, G. Y.

AU - Wang, H.

AU - Fong, David W F

PY - 2010/7

Y1 - 2010/7

N2 - We studied the effects of schisandrol A (SCH) and gomisin A (GOM), two of the main bioactive components of Fructus Schisandrae chinensis, on cytochrome P450-3A4 (CYP3A4) activity and cellular glutathione (GSH) level. In a cell-free system both SCH and GOM inhibited CYP3A4 activity with IC50 values of 32.02 μM and 1.39 μM, respectively. SCH or GOM at concentrations up to 100 μM did not alter cellular GSH level in regular HepG2 cells and P-glycoprotein overexpressing HepG2-DR cells. Since SCH and GOM may reverse multidrug resistance (MDR) by impeding the activity of P-glycoprotein, a membrane xenobiotic exporter, SCH or GOM could affect cellular drug metabolism in addition to drug uptake.

AB - We studied the effects of schisandrol A (SCH) and gomisin A (GOM), two of the main bioactive components of Fructus Schisandrae chinensis, on cytochrome P450-3A4 (CYP3A4) activity and cellular glutathione (GSH) level. In a cell-free system both SCH and GOM inhibited CYP3A4 activity with IC50 values of 32.02 μM and 1.39 μM, respectively. SCH or GOM at concentrations up to 100 μM did not alter cellular GSH level in regular HepG2 cells and P-glycoprotein overexpressing HepG2-DR cells. Since SCH and GOM may reverse multidrug resistance (MDR) by impeding the activity of P-glycoprotein, a membrane xenobiotic exporter, SCH or GOM could affect cellular drug metabolism in addition to drug uptake.

KW - Cytochrome P450 3A4

KW - Glutathione

KW - Gomisin A

KW - Multidrug resistance

KW - Schisandra chinensis

KW - Schisandrol A

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U2 - 10.1016/j.phymed.2009.12.005

DO - 10.1016/j.phymed.2009.12.005

M3 - Journal article

C2 - 20089387

AN - SCOPUS:77952290102

SN - 0944-7113

VL - 17

SP - 702

EP - 705

JO - Phytomedicine

JF - Phytomedicine

IS - 8-9

ER -

Inhibition of cytochrome P450 3A4 activity by schisandrol A and gomisin A isolated from Fructus Schisandrae chinensis

Abstract

Scopus Subject Areas

User-Defined Keywords

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