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Research ArticleArticle

Identification and Characterization of Potent CYP2B6 Inhibitors in Woohwangcheongsimwon Suspension, an Herbal Preparation Used in the Treatment and Prevention of Apoplexy in Korea and China

Hyunmi Kim, Kwon-Bok Kim, Hei-Young Ku, Soo-Jin Park, Hoon Choi, Joon-Kwan Moon, Byeoung-Soo Park, Jeong-Han Kim, Sung Su Yea, Choong-Hwan Lee, Hye Suk Lee, Jae-Gook Shin and Kwang-Hyeon Liu
Drug Metabolism and Disposition June 2008, 36 (6) 1010-1015; DOI: https://doi.org/10.1124/dmd.107.019612
Hyunmi Kim
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Kwon-Bok Kim
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Hei-Young Ku
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Soo-Jin Park
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Hoon Choi
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Joon-Kwan Moon
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Byeoung-Soo Park
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Jeong-Han Kim
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Sung Su Yea
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Choong-Hwan Lee
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Hye Suk Lee
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Jae-Gook Shin
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Kwang-Hyeon Liu
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This article has a correction. Please see:

  • CORRECTION TO “IDENTIFICATION AND CHARACTERIZATION OF POTENT CYP2B6 INHIBITORS IN WOOHWANGCHEONGSIMWON SUSPENSION, AN HERBAL PREPARATION USED IN THE TREATMENT AND PREVENTION OF APOPLEXY IN KOREA AND CHINA” - August 01, 2008

Abstract

Woohwangcheongsimwon is a traditional medicine for treating hypertension, arteriosclerosis, coma, and stroke in China and Korea. To assess potential interactions of herb and drug metabolism, commercially available Woohwangcheongsimwon suspensions were examined for their potential to inhibit the activity of nine human cytochrome P450 enzymes. The Woohwangcheongsimwon suspensions showed strong inhibition of CYP2B6 activity. To identify individual constituents with inhibitory activity, the suspension was partitioned using hexane, ethyl acetate, and dichloromethane, and each fraction was tested for its inhibitory effect on CYP2B6-catalyzed bupropion hydroxylation. The hexane fraction possessed inhibitory activity, and gas chromatography/mass spectrometry analysis identified borneol and isoborneol as major constituents of the hexane fraction. These two terpenoids moderately inhibited CYP2B6-catalyzed bupropion hydroxylase activity in a competitive manner, with Ki values of 9.5 and 5.9 μM, respectively, as well as efavirenz 8-hydroxylase activity, with Ki values of 22 and 26 μM, respectively. Additionally, reconstituted mixtures of borneol and isoborneol, at the same concentrations as in the Woohwangcheongsimwon suspension, had comparable potency in inhibiting bupropion hydroxylation. These in vitro data indicate that Woohwangcheongsimwon preparations contain constituents that can potently inhibit the activity of CYP2B6 and suggest that these preparations should be examined for potential pharmacokinetic drug interactions in vivo.

Footnotes

  • This study was supported by the Korea Research Foundation Grant funded by the Korean Government (MODHRD, Basic Research Promotion Fund) (KRF-2006-311-E00238) and by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (R13-2007-023-00000-0), Korea.

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.107.019612.

  • ABBREVIATIONS: P450, cytochrome P450; thiotepa, triethylenethiophoramide; LC, liquid chromatography; MS/MS, tandem mass spectrometry; GC, gas chromatography; MS, mass spectrometry.

    • Received November 1, 2007.
    • Accepted March 5, 2008.
  • The American Society for Pharmacology and Experimental Therapeutics
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Drug Metabolism and Disposition: 36 (6)
Drug Metabolism and Disposition
Vol. 36, Issue 6
1 Jun 2008
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Research ArticleArticle

Identification and Characterization of Potent CYP2B6 Inhibitors in Woohwangcheongsimwon Suspension, an Herbal Preparation Used in the Treatment and Prevention of Apoplexy in Korea and China

Hyunmi Kim, Kwon-Bok Kim, Hei-Young Ku, Soo-Jin Park, Hoon Choi, Joon-Kwan Moon, Byeoung-Soo Park, Jeong-Han Kim, Sung Su Yea, Choong-Hwan Lee, Hye Suk Lee, Jae-Gook Shin and Kwang-Hyeon Liu
Drug Metabolism and Disposition June 1, 2008, 36 (6) 1010-1015; DOI: https://doi.org/10.1124/dmd.107.019612

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Research ArticleArticle

Identification and Characterization of Potent CYP2B6 Inhibitors in Woohwangcheongsimwon Suspension, an Herbal Preparation Used in the Treatment and Prevention of Apoplexy in Korea and China

Hyunmi Kim, Kwon-Bok Kim, Hei-Young Ku, Soo-Jin Park, Hoon Choi, Joon-Kwan Moon, Byeoung-Soo Park, Jeong-Han Kim, Sung Su Yea, Choong-Hwan Lee, Hye Suk Lee, Jae-Gook Shin and Kwang-Hyeon Liu
Drug Metabolism and Disposition June 1, 2008, 36 (6) 1010-1015; DOI: https://doi.org/10.1124/dmd.107.019612
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