Comparison of metabolism of sesamin and episesamin by drug-metabolizing enzymes in human liver

Kaori Yasuda, Shinichi Ikushiro, Shuto Wakayama, Toshimasa Itoh, Keiko Yamamoto, Masaki Kamakura, Eiji Munetsuna, Miho Ohta, Toshiyuki Sakaki

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Sesamin and episesamin are two epimeric lignans that are found in refined sesame oil. Commercially available sesamin supplements contain both sesamin and episesamin at an approximate 1:1 ratio. Our previous study clarified the sequential metabolism of sesamin by cytochrome P450 (P450) and UDP-glucuronosyltransferase in human liver. In addition, we revealed that sesamin caused a mechanism-based inhibition (MBI) of CYP2C9, the P450 enzyme responsible for sesamin monocatecholization. In the present study, we compared the metabolism and the MBI of episesamin with those of sesamin. Episesamin was first metabolized to the two epimers of monocatechol, S- and R-monocatechols in human liver microsomes. The P450 enzymes responsible for S- and R-monocatechol formation were CYP2C9 and CYP1A2, respectively. The contribution of CYP2C9 was much larger than that of CYP1A2 in sesamin metabolism, whereas the contribution of CYP2C9 was almost equal to that of CYP1A2 in episesamin metabolism. Docking of episesamin to the active site of CYP1A2 explained the stereoselectivity in CYP1A2-dependent episesamin monocatecholization. Similar to sesamin, the episesamin S- and R-monocatechols were further metabolized to dicatechol, glucuronide, and methylate metabolites in human liver; however, the contribution of each reaction was significantly different between sesamin and episesamin. The liver microsomes from CYP2C19 ultra-rapid metabolizers showed a significant amount of episesamin dicatechol. In this study, we have revealed significantly different metabolism by P450, UDP-glucuronosyltransferase, and catechol-O-methyltransferase for sesamin and episesamin, resulting in different biological effects.

Original languageEnglish
Pages (from-to)1917-1926
Number of pages10
JournalDrug Metabolism and Disposition
Volume40
Issue number10
DOIs
Publication statusPublished - 01-10-2012

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Liver
Enzymes
Pharmaceutical Preparations
Cytochrome P-450 CYP1A2
sesamin
Cytochrome P-450 Enzyme System
Glucuronosyltransferase
Liver Microsomes
Sesame Oil
Catechol O-Methyltransferase
Lignans
Glucuronides
Catalytic Domain

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

Cite this

Yasuda, K., Ikushiro, S., Wakayama, S., Itoh, T., Yamamoto, K., Kamakura, M., ... Sakaki, T. (2012). Comparison of metabolism of sesamin and episesamin by drug-metabolizing enzymes in human liver. Drug Metabolism and Disposition, 40(10), 1917-1926. https://doi.org/10.1124/dmd.112.045906
Yasuda, Kaori ; Ikushiro, Shinichi ; Wakayama, Shuto ; Itoh, Toshimasa ; Yamamoto, Keiko ; Kamakura, Masaki ; Munetsuna, Eiji ; Ohta, Miho ; Sakaki, Toshiyuki. / Comparison of metabolism of sesamin and episesamin by drug-metabolizing enzymes in human liver. In: Drug Metabolism and Disposition. 2012 ; Vol. 40, No. 10. pp. 1917-1926.
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Yasuda, K, Ikushiro, S, Wakayama, S, Itoh, T, Yamamoto, K, Kamakura, M, Munetsuna, E, Ohta, M & Sakaki, T 2012, 'Comparison of metabolism of sesamin and episesamin by drug-metabolizing enzymes in human liver', Drug Metabolism and Disposition, vol. 40, no. 10, pp. 1917-1926. https://doi.org/10.1124/dmd.112.045906

Comparison of metabolism of sesamin and episesamin by drug-metabolizing enzymes in human liver. / Yasuda, Kaori; Ikushiro, Shinichi; Wakayama, Shuto; Itoh, Toshimasa; Yamamoto, Keiko; Kamakura, Masaki; Munetsuna, Eiji; Ohta, Miho; Sakaki, Toshiyuki.

In: Drug Metabolism and Disposition, Vol. 40, No. 10, 01.10.2012, p. 1917-1926.

Research output: Contribution to journalArticle

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AU - Yasuda, Kaori

AU - Ikushiro, Shinichi

AU - Wakayama, Shuto

AU - Itoh, Toshimasa

AU - Yamamoto, Keiko

AU - Kamakura, Masaki

AU - Munetsuna, Eiji

AU - Ohta, Miho

AU - Sakaki, Toshiyuki

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