Induction of cytochrome P450-dependent monooxygenase by extracts of the medicinal herb Salvia miltiorrhiza

Ya Hui Kuo, Yun Lian Lin, Ming Jaw Don, Ruei Ming Chen, Yune Fang Ueng

Research output: Contribution to journalArticle

49 Citations (Scopus)

Abstract

The herbal medicine Salvia miltiorrhiza (Danshen) is currently used for the treatment of cardiovascular and cerebrovascular diseases. To assess possible herb-drug interactions, the effects of the aqueous and ethyl acetate extracts of S. miltiorrhiza on cytochrome P450 (CYP) were studied. Oral treatment of C57BL/6J mice with the ethyl acetate extract caused a dose-dependent increase in liver microsomal 7-methoxyresorufin O-demethylation (MROD) activity. The ethyl acetate extract caused an 8-, 2-, 3- and 3-fold increase in hepatic MROD, tolbutamide hydroxylation, nifedipine oxidation and warfarin 7-hydroxylation activity, respectively. However, the aqueous extract had no effects on any of the activities determined. Pharmaceutical product of S. miltiorrhiza extract caused a dose-dependent increase in MROD activity without affecting other activity. Immunoblot analysis of microsomal proteins showed that ethyl acetate extract-treatment elevated the protein levels of CYP1A and CYP3A. Tanshinone IIA was the main diterpene quinone in S. miltiorrhiza. At the dose corresponding to its content in ethyl acetate extract, tanshinone IIA-treatment increased mouse liver microsomal MROD activity. These results demonstrated that there were mouse CYP1A, CYP2C and CYP3A-inducing agents present in the ethyl acetate extract, but not in the aqueous extract, of S. miltiorrhiza. Tanshinone IIA played a role in the induction of CYP1A by S. miltiorrhiza. The CYP induction by the ethyl acetate extract and pharmaceutical product suggested that possible drug interactions between S. miltiorrhiza and CYP substrates should be noticed.

Original languageEnglish
Pages (from-to)521-527
Number of pages7
JournalJournal of Pharmacy and Pharmacology
Volume58
Issue number4
DOIs
Publication statusPublished - Apr 2006

Fingerprint

Salvia miltiorrhiza
Medicinal Plants
Mixed Function Oxygenases
Cytochrome P-450 Enzyme System
Cytochrome P-450 CYP3A
Hydroxylation
Liver
Herb-Drug Interactions
Cerebrovascular Disorders
Tolbutamide
Herbal Medicine
Diterpenes
Warfarin
Nifedipine
ethyl acetate
Drug Interactions
Inbred C57BL Mouse
Pharmaceutical Preparations
Proteins
Cardiovascular Diseases

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Induction of cytochrome P450-dependent monooxygenase by extracts of the medicinal herb Salvia miltiorrhiza. / Kuo, Ya Hui; Lin, Yun Lian; Don, Ming Jaw; Chen, Ruei Ming; Ueng, Yune Fang.

In: Journal of Pharmacy and Pharmacology, Vol. 58, No. 4, 04.2006, p. 521-527.

Research output: Contribution to journalArticle

Kuo, Ya Hui ; Lin, Yun Lian ; Don, Ming Jaw ; Chen, Ruei Ming ; Ueng, Yune Fang. / Induction of cytochrome P450-dependent monooxygenase by extracts of the medicinal herb Salvia miltiorrhiza. In: Journal of Pharmacy and Pharmacology. 2006 ; Vol. 58, No. 4. pp. 521-527.
@article{a831f5bb339141ecb6a84642d0a3e330,
title = "Induction of cytochrome P450-dependent monooxygenase by extracts of the medicinal herb Salvia miltiorrhiza",
abstract = "The herbal medicine Salvia miltiorrhiza (Danshen) is currently used for the treatment of cardiovascular and cerebrovascular diseases. To assess possible herb-drug interactions, the effects of the aqueous and ethyl acetate extracts of S. miltiorrhiza on cytochrome P450 (CYP) were studied. Oral treatment of C57BL/6J mice with the ethyl acetate extract caused a dose-dependent increase in liver microsomal 7-methoxyresorufin O-demethylation (MROD) activity. The ethyl acetate extract caused an 8-, 2-, 3- and 3-fold increase in hepatic MROD, tolbutamide hydroxylation, nifedipine oxidation and warfarin 7-hydroxylation activity, respectively. However, the aqueous extract had no effects on any of the activities determined. Pharmaceutical product of S. miltiorrhiza extract caused a dose-dependent increase in MROD activity without affecting other activity. Immunoblot analysis of microsomal proteins showed that ethyl acetate extract-treatment elevated the protein levels of CYP1A and CYP3A. Tanshinone IIA was the main diterpene quinone in S. miltiorrhiza. At the dose corresponding to its content in ethyl acetate extract, tanshinone IIA-treatment increased mouse liver microsomal MROD activity. These results demonstrated that there were mouse CYP1A, CYP2C and CYP3A-inducing agents present in the ethyl acetate extract, but not in the aqueous extract, of S. miltiorrhiza. Tanshinone IIA played a role in the induction of CYP1A by S. miltiorrhiza. The CYP induction by the ethyl acetate extract and pharmaceutical product suggested that possible drug interactions between S. miltiorrhiza and CYP substrates should be noticed.",
author = "Kuo, {Ya Hui} and Lin, {Yun Lian} and Don, {Ming Jaw} and Chen, {Ruei Ming} and Ueng, {Yune Fang}",
year = "2006",
month = "4",
doi = "10.1211/jpp.58.4.0012",
language = "English",
volume = "58",
pages = "521--527",
journal = "Journal of Pharmacy and Pharmacology",
issn = "0022-3573",
publisher = "Pharmaceutical Press",
number = "4",

}

TY - JOUR

T1 - Induction of cytochrome P450-dependent monooxygenase by extracts of the medicinal herb Salvia miltiorrhiza

AU - Kuo, Ya Hui

AU - Lin, Yun Lian

AU - Don, Ming Jaw

AU - Chen, Ruei Ming

AU - Ueng, Yune Fang

PY - 2006/4

Y1 - 2006/4

N2 - The herbal medicine Salvia miltiorrhiza (Danshen) is currently used for the treatment of cardiovascular and cerebrovascular diseases. To assess possible herb-drug interactions, the effects of the aqueous and ethyl acetate extracts of S. miltiorrhiza on cytochrome P450 (CYP) were studied. Oral treatment of C57BL/6J mice with the ethyl acetate extract caused a dose-dependent increase in liver microsomal 7-methoxyresorufin O-demethylation (MROD) activity. The ethyl acetate extract caused an 8-, 2-, 3- and 3-fold increase in hepatic MROD, tolbutamide hydroxylation, nifedipine oxidation and warfarin 7-hydroxylation activity, respectively. However, the aqueous extract had no effects on any of the activities determined. Pharmaceutical product of S. miltiorrhiza extract caused a dose-dependent increase in MROD activity without affecting other activity. Immunoblot analysis of microsomal proteins showed that ethyl acetate extract-treatment elevated the protein levels of CYP1A and CYP3A. Tanshinone IIA was the main diterpene quinone in S. miltiorrhiza. At the dose corresponding to its content in ethyl acetate extract, tanshinone IIA-treatment increased mouse liver microsomal MROD activity. These results demonstrated that there were mouse CYP1A, CYP2C and CYP3A-inducing agents present in the ethyl acetate extract, but not in the aqueous extract, of S. miltiorrhiza. Tanshinone IIA played a role in the induction of CYP1A by S. miltiorrhiza. The CYP induction by the ethyl acetate extract and pharmaceutical product suggested that possible drug interactions between S. miltiorrhiza and CYP substrates should be noticed.

AB - The herbal medicine Salvia miltiorrhiza (Danshen) is currently used for the treatment of cardiovascular and cerebrovascular diseases. To assess possible herb-drug interactions, the effects of the aqueous and ethyl acetate extracts of S. miltiorrhiza on cytochrome P450 (CYP) were studied. Oral treatment of C57BL/6J mice with the ethyl acetate extract caused a dose-dependent increase in liver microsomal 7-methoxyresorufin O-demethylation (MROD) activity. The ethyl acetate extract caused an 8-, 2-, 3- and 3-fold increase in hepatic MROD, tolbutamide hydroxylation, nifedipine oxidation and warfarin 7-hydroxylation activity, respectively. However, the aqueous extract had no effects on any of the activities determined. Pharmaceutical product of S. miltiorrhiza extract caused a dose-dependent increase in MROD activity without affecting other activity. Immunoblot analysis of microsomal proteins showed that ethyl acetate extract-treatment elevated the protein levels of CYP1A and CYP3A. Tanshinone IIA was the main diterpene quinone in S. miltiorrhiza. At the dose corresponding to its content in ethyl acetate extract, tanshinone IIA-treatment increased mouse liver microsomal MROD activity. These results demonstrated that there were mouse CYP1A, CYP2C and CYP3A-inducing agents present in the ethyl acetate extract, but not in the aqueous extract, of S. miltiorrhiza. Tanshinone IIA played a role in the induction of CYP1A by S. miltiorrhiza. The CYP induction by the ethyl acetate extract and pharmaceutical product suggested that possible drug interactions between S. miltiorrhiza and CYP substrates should be noticed.

UR - http://www.scopus.com/inward/record.url?scp=33645564707&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645564707&partnerID=8YFLogxK

U2 - 10.1211/jpp.58.4.0012

DO - 10.1211/jpp.58.4.0012

M3 - Article

C2 - 16597370

AN - SCOPUS:33645564707

VL - 58

SP - 521

EP - 527

JO - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

SN - 0022-3573

IS - 4

ER -