Berberine improved experimental chronic colitis by regulating interferon-γ- and IL-17A-producing lamina propria CD4+ T cells through AMPK activation

Masahiro Takahara, Akinobu Takaki, Sakiko Hiraoka, Takuya Adachi, Yasuyuki Shimomura, Hiroshi Matsushita, Tien Thi Thuy Nguyen, Kazuko Koike, Airi Ikeda, Shiho Takashima, Yasushi Yamasaki, Toshihiro Inokuchi, Hideaki Kunugasa, Yusaku Sugihara, Keita Harada, Shingo Eikawa, Hidetoshi Morita, Heiichiro Udono, Hiroyuki Okada

Research output: Contribution to journalArticle

Abstract

The herbal medicine berberine (BBR) has been recently shown to be an AMP-activated protein kinase (AMPK) productive activator with various properties that induce anti-inflammatory responses. We investigated the effects of BBR on the mechanisms of mucosal CD4+T cell activation in vitro and on the inflammatory responses in T cell transfer mouse models of inflammatory bowel disease (IBD). We examined the favorable effects of BBR in vitro, using lamina propria (LP) CD4+ T cells in T cell transfer IBD models in which SCID mice had been injected with CD4+CD45RBhigh T cells. BBR suppressed the frequency of IFN-γ- and Il-17A-producing LP CD4+ T cells. This effect was found to be regulated by AMPK activation possibly induced by oxidative phosphorylation inhibition. We then examined the effects of BBR on the same IBD models in vivo. BBR-fed mice showed AMPK activation in the LPCD4+ T cells and an improvement of colitis. Our study newly showed that the BBR-induced AMPK activation of mucosal CD4+ T cells resulted in an improvement of IBD and underscored the importance of AMPK activity in colonic inflammation.

Original languageEnglish
Article number11934
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

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Berberine
AMP-Activated Protein Kinases
Interleukin-17
Colitis
Interferons
Mucous Membrane
T-Lymphocytes
Inflammatory Bowel Diseases
SCID Mice
Herbal Medicine
Oxidative Phosphorylation
Anti-Inflammatory Agents
Inflammation

ASJC Scopus subject areas

  • General

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Berberine improved experimental chronic colitis by regulating interferon-γ- and IL-17A-producing lamina propria CD4+ T cells through AMPK activation. / Takahara, Masahiro; Takaki, Akinobu; Hiraoka, Sakiko; Adachi, Takuya; Shimomura, Yasuyuki; Matsushita, Hiroshi; Nguyen, Tien Thi Thuy; Koike, Kazuko; Ikeda, Airi; Takashima, Shiho; Yamasaki, Yasushi; Inokuchi, Toshihiro; Kunugasa, Hideaki; Sugihara, Yusaku; Harada, Keita; Eikawa, Shingo; Morita, Hidetoshi; Udono, Heiichiro; Okada, Hiroyuki.

In: Scientific reports, Vol. 9, No. 1, 11934, 01.12.2019.

Research output: Contribution to journalArticle

Takahara, M, Takaki, A, Hiraoka, S, Adachi, T, Shimomura, Y, Matsushita, H, Nguyen, TTT, Koike, K, Ikeda, A, Takashima, S, Yamasaki, Y, Inokuchi, T, Kunugasa, H, Sugihara, Y, Harada, K, Eikawa, S, Morita, H, Udono, H & Okada, H 2019, 'Berberine improved experimental chronic colitis by regulating interferon-γ- and IL-17A-producing lamina propria CD4+ T cells through AMPK activation', Scientific reports, vol. 9, no. 1, 11934. https://doi.org/10.1038/s41598-019-48331-w
Takahara, Masahiro ; Takaki, Akinobu ; Hiraoka, Sakiko ; Adachi, Takuya ; Shimomura, Yasuyuki ; Matsushita, Hiroshi ; Nguyen, Tien Thi Thuy ; Koike, Kazuko ; Ikeda, Airi ; Takashima, Shiho ; Yamasaki, Yasushi ; Inokuchi, Toshihiro ; Kunugasa, Hideaki ; Sugihara, Yusaku ; Harada, Keita ; Eikawa, Shingo ; Morita, Hidetoshi ; Udono, Heiichiro ; Okada, Hiroyuki. / Berberine improved experimental chronic colitis by regulating interferon-γ- and IL-17A-producing lamina propria CD4+ T cells through AMPK activation. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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