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Title: Citrus nobiletin suppresses inducible nitric oxide synthase gene expression in interleukin-1β-treated hepatocytes

Abstract

Highlights: •Nobiletin is a polymethoxylated flavone that is abundant in citrus peels. •Nobiletin is a major constituent of the Citrus unshiu peel extract. •Nobiletin suppresses induction of NO and reduces iNOS expression in hepatocytes. •Nobiletin reduces the iNOS promoter activity and the DNA-binding activity of NF-κB. -- Abstract: Background: Nobiletin is a polymethoxylated flavone that is abundant in the peels of citrus fruits, such as Citrus unshiu (Satsuma mandarin) and Citrus sinensis. The dried peels of C. unshiu (chinpi) have been included in several formulae of Japanese Kampo medicines. Nobiletin may suppress the induction of inducible nitric oxide synthase (iNOS), which synthesizes the inflammatory mediator nitric oxide (NO) in hepatocytes. Methods: A C. unshiu peel (CUP) extract was prepared. Primary cultured rat hepatocytes were treated with the CUP extract or nobiletin in the presence of interleukin 1β (IL-1β), which induces iNOS expression. NO production and iNOS gene expression were analyzed. Results: High-performance liquid chromatography analyses revealed that the nobiletin content in the CUP extract was 0.14%. Nobiletin dose-dependently reduced the NO levels and decreased iNOS expression at the protein, mRNA and antisense transcript levels. Flavone, which does not contain any methoxy groups, also suppressed iNOS induction. Nobiletin reduced the transcriptionalmore » activity of iNOS promoter-luciferase constructs and the DNA-binding activity of nuclear factor κB (NF-κB) in the nuclei. Conclusions: The suppression of iNOS induction by nobiletin suggests that nobiletin may be responsible for the anti-inflammatory effects of citrus peels and have a therapeutic potential for liver diseases.« less

Authors:
 [1];  [1];  [2]; ; ;  [1];  [3];  [4];  [2];  [1]
  1. Department of Biomedical Sciences, College of Life Sciences, Kusatsu, Shiga (Japan)
  2. Ritsumeikan Global Innovation Research Organization (R-GIRO), Kusatsu, Shiga (Japan)
  3. Research Organization of Science and Technology, Ritsumeikan University, Kusatsu, Shiga (Japan)
  4. Department of Pharmacy, College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga (Japan)
Publication Date:
OSTI Identifier:
22242093
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 439; Journal Issue: 1; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CITRUS; DNA; GENES; HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY; INDUCTION; INFLAMMATION; LIVER; LIVER CELLS; LUCIFERASE; MESSENGER-RNA; NITRIC OXIDE; RATS

Citation Formats

Yoshigai, Emi, Ritsumeikan Global Innovation Research Organization, Machida, Toru, Okuyama, Tetsuya, Mori, Masatoshi, Murase, Hiromitsu, Yamanishi, Ryota, Okumura, Tadayoshi, Department of Surgery, Kansai Medical University, Hirakata, Osaka, Ikeya, Yukinobu, Nishino, Hoyoku, Department of Biochemistry, Kyoto Prefectural University of Medicine, Kyoto, and Nishizawa, Mikio. Citrus nobiletin suppresses inducible nitric oxide synthase gene expression in interleukin-1β-treated hepatocytes. United States: N. p., 2013. Web. doi:10.1016/J.BBRC.2013.08.029.
Yoshigai, Emi, Ritsumeikan Global Innovation Research Organization, Machida, Toru, Okuyama, Tetsuya, Mori, Masatoshi, Murase, Hiromitsu, Yamanishi, Ryota, Okumura, Tadayoshi, Department of Surgery, Kansai Medical University, Hirakata, Osaka, Ikeya, Yukinobu, Nishino, Hoyoku, Department of Biochemistry, Kyoto Prefectural University of Medicine, Kyoto, & Nishizawa, Mikio. Citrus nobiletin suppresses inducible nitric oxide synthase gene expression in interleukin-1β-treated hepatocytes. United States. https://doi.org/10.1016/J.BBRC.2013.08.029
Yoshigai, Emi, Ritsumeikan Global Innovation Research Organization, Machida, Toru, Okuyama, Tetsuya, Mori, Masatoshi, Murase, Hiromitsu, Yamanishi, Ryota, Okumura, Tadayoshi, Department of Surgery, Kansai Medical University, Hirakata, Osaka, Ikeya, Yukinobu, Nishino, Hoyoku, Department of Biochemistry, Kyoto Prefectural University of Medicine, Kyoto, and Nishizawa, Mikio. 2013. "Citrus nobiletin suppresses inducible nitric oxide synthase gene expression in interleukin-1β-treated hepatocytes". United States. https://doi.org/10.1016/J.BBRC.2013.08.029.
@article{osti_22242093,
title = {Citrus nobiletin suppresses inducible nitric oxide synthase gene expression in interleukin-1β-treated hepatocytes},
author = {Yoshigai, Emi and Ritsumeikan Global Innovation Research Organization and Machida, Toru and Okuyama, Tetsuya and Mori, Masatoshi and Murase, Hiromitsu and Yamanishi, Ryota and Okumura, Tadayoshi and Department of Surgery, Kansai Medical University, Hirakata, Osaka and Ikeya, Yukinobu and Nishino, Hoyoku and Department of Biochemistry, Kyoto Prefectural University of Medicine, Kyoto and Nishizawa, Mikio},
abstractNote = {Highlights: •Nobiletin is a polymethoxylated flavone that is abundant in citrus peels. •Nobiletin is a major constituent of the Citrus unshiu peel extract. •Nobiletin suppresses induction of NO and reduces iNOS expression in hepatocytes. •Nobiletin reduces the iNOS promoter activity and the DNA-binding activity of NF-κB. -- Abstract: Background: Nobiletin is a polymethoxylated flavone that is abundant in the peels of citrus fruits, such as Citrus unshiu (Satsuma mandarin) and Citrus sinensis. The dried peels of C. unshiu (chinpi) have been included in several formulae of Japanese Kampo medicines. Nobiletin may suppress the induction of inducible nitric oxide synthase (iNOS), which synthesizes the inflammatory mediator nitric oxide (NO) in hepatocytes. Methods: A C. unshiu peel (CUP) extract was prepared. Primary cultured rat hepatocytes were treated with the CUP extract or nobiletin in the presence of interleukin 1β (IL-1β), which induces iNOS expression. NO production and iNOS gene expression were analyzed. Results: High-performance liquid chromatography analyses revealed that the nobiletin content in the CUP extract was 0.14%. Nobiletin dose-dependently reduced the NO levels and decreased iNOS expression at the protein, mRNA and antisense transcript levels. Flavone, which does not contain any methoxy groups, also suppressed iNOS induction. Nobiletin reduced the transcriptional activity of iNOS promoter-luciferase constructs and the DNA-binding activity of nuclear factor κB (NF-κB) in the nuclei. Conclusions: The suppression of iNOS induction by nobiletin suggests that nobiletin may be responsible for the anti-inflammatory effects of citrus peels and have a therapeutic potential for liver diseases.},
doi = {10.1016/J.BBRC.2013.08.029},
url = {https://www.osti.gov/biblio/22242093}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 1,
volume = 439,
place = {United States},
year = {Fri Sep 13 00:00:00 EDT 2013},
month = {Fri Sep 13 00:00:00 EDT 2013}
}