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Conophylline inhibits non-alcoholic steatohepatitis in mice

Conophylline (CnP), a vinca alkaloid extracted from the leaves of the tropical plant Ervatamia microphylla, attenuates hepatic fibrosis in mice. However, little is known about whether CnP inhibits steatosis, inflammation, and fibrosis in non-alcoholic steatohepatitis (NASH) in mice. A methionine-cho...

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Autores principales: Nakade, Yukiomi, Sakamoto, Kazumasa, Yamauchi, Taeko, Inoue, Tadahisa, Kobayashi, Yuji, Yamamoto, Takaya, Ishii, Norimitsu, Ohashi, Tomohiko, Sumida, Yoshio, Ito, Kiyoaki, Nakao, Haruhisa, Fukuzawa, Yoshitaka, Umezawa, Kazuo, Yoneda, Masashi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464552/
https://www.ncbi.nlm.nih.gov/pubmed/28594915
http://dx.doi.org/10.1371/journal.pone.0178436
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author Nakade, Yukiomi
Sakamoto, Kazumasa
Yamauchi, Taeko
Inoue, Tadahisa
Kobayashi, Yuji
Yamamoto, Takaya
Ishii, Norimitsu
Ohashi, Tomohiko
Sumida, Yoshio
Ito, Kiyoaki
Nakao, Haruhisa
Fukuzawa, Yoshitaka
Umezawa, Kazuo
Yoneda, Masashi
author_facet Nakade, Yukiomi
Sakamoto, Kazumasa
Yamauchi, Taeko
Inoue, Tadahisa
Kobayashi, Yuji
Yamamoto, Takaya
Ishii, Norimitsu
Ohashi, Tomohiko
Sumida, Yoshio
Ito, Kiyoaki
Nakao, Haruhisa
Fukuzawa, Yoshitaka
Umezawa, Kazuo
Yoneda, Masashi
author_sort Nakade, Yukiomi
collection PubMed
description Conophylline (CnP), a vinca alkaloid extracted from the leaves of the tropical plant Ervatamia microphylla, attenuates hepatic fibrosis in mice. However, little is known about whether CnP inhibits steatosis, inflammation, and fibrosis in non-alcoholic steatohepatitis (NASH) in mice. A methionine-choline-deficient (MCD) diet was administered to male db/db mice as a NASH model, and CnP (1 μg/kg/d) was co-administered. Eight weeks after the commencement of the MCD diet, hepatic steatosis, inflammation, and fibrosis, and hepatic fat metabolism-, inflammation-, and fibrosis-related markers were examined. Feeding on an MCD for 8 weeks induced hepatic steatosis, inflammation, and fibrosis. CnP significantly attenuated the MCD-induced increases in hepatic steatosis, as well as hepatic inflammation and fibrosis. The MCD diet increased hepatic transforming growth factor-β (TGF-β) mRNA levels, which are correlated with hepatic steatosis, inflammation, and fibrosis. The diet also attenuated acyl-coenzyme A oxidase 1 (ACOX1) and carnitine palmitoyltransferase 1 (CPT1) mRNA levels, which are involved in β-oxidation. The putative mechanism of the CnP effect involves reduced hepatic TGF-β mRNA levels, and increased mRNA levels of hepatic peroxisome proliferator-activated receptor (PPAR) α and its target genes ACOX1 and CPT1. The results of this study indicate that CnP inhibits steatohepatitis, possibly through the inhibition of hepatic TGF-β mRNA levels, and induces an increase in PPARα mRNA levels, resulting in the attenuation of hepatic steatosis, inflammation, and fibrosis in mice. CnP might accordingly be a suitable therapeutic option for NASH.
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spelling pubmed-54645522017-06-22 Conophylline inhibits non-alcoholic steatohepatitis in mice Nakade, Yukiomi Sakamoto, Kazumasa Yamauchi, Taeko Inoue, Tadahisa Kobayashi, Yuji Yamamoto, Takaya Ishii, Norimitsu Ohashi, Tomohiko Sumida, Yoshio Ito, Kiyoaki Nakao, Haruhisa Fukuzawa, Yoshitaka Umezawa, Kazuo Yoneda, Masashi PLoS One Research Article Conophylline (CnP), a vinca alkaloid extracted from the leaves of the tropical plant Ervatamia microphylla, attenuates hepatic fibrosis in mice. However, little is known about whether CnP inhibits steatosis, inflammation, and fibrosis in non-alcoholic steatohepatitis (NASH) in mice. A methionine-choline-deficient (MCD) diet was administered to male db/db mice as a NASH model, and CnP (1 μg/kg/d) was co-administered. Eight weeks after the commencement of the MCD diet, hepatic steatosis, inflammation, and fibrosis, and hepatic fat metabolism-, inflammation-, and fibrosis-related markers were examined. Feeding on an MCD for 8 weeks induced hepatic steatosis, inflammation, and fibrosis. CnP significantly attenuated the MCD-induced increases in hepatic steatosis, as well as hepatic inflammation and fibrosis. The MCD diet increased hepatic transforming growth factor-β (TGF-β) mRNA levels, which are correlated with hepatic steatosis, inflammation, and fibrosis. The diet also attenuated acyl-coenzyme A oxidase 1 (ACOX1) and carnitine palmitoyltransferase 1 (CPT1) mRNA levels, which are involved in β-oxidation. The putative mechanism of the CnP effect involves reduced hepatic TGF-β mRNA levels, and increased mRNA levels of hepatic peroxisome proliferator-activated receptor (PPAR) α and its target genes ACOX1 and CPT1. The results of this study indicate that CnP inhibits steatohepatitis, possibly through the inhibition of hepatic TGF-β mRNA levels, and induces an increase in PPARα mRNA levels, resulting in the attenuation of hepatic steatosis, inflammation, and fibrosis in mice. CnP might accordingly be a suitable therapeutic option for NASH. Public Library of Science 2017-06-08 /pmc/articles/PMC5464552/ /pubmed/28594915 http://dx.doi.org/10.1371/journal.pone.0178436 Text en © 2017 Nakade et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Nakade, Yukiomi
Sakamoto, Kazumasa
Yamauchi, Taeko
Inoue, Tadahisa
Kobayashi, Yuji
Yamamoto, Takaya
Ishii, Norimitsu
Ohashi, Tomohiko
Sumida, Yoshio
Ito, Kiyoaki
Nakao, Haruhisa
Fukuzawa, Yoshitaka
Umezawa, Kazuo
Yoneda, Masashi
Conophylline inhibits non-alcoholic steatohepatitis in mice
title Conophylline inhibits non-alcoholic steatohepatitis in mice
title_full Conophylline inhibits non-alcoholic steatohepatitis in mice
title_fullStr Conophylline inhibits non-alcoholic steatohepatitis in mice
title_full_unstemmed Conophylline inhibits non-alcoholic steatohepatitis in mice
title_short Conophylline inhibits non-alcoholic steatohepatitis in mice
title_sort conophylline inhibits non-alcoholic steatohepatitis in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464552/
https://www.ncbi.nlm.nih.gov/pubmed/28594915
http://dx.doi.org/10.1371/journal.pone.0178436
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