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Effects of Chinese Medicinal Formula BNG-1 on Phosphodiesterase 3B Expression, Hepatic Steatosis, and Insulin Resistance in High Fat Diet-induced NAFLD Mice

Background: Chinese medicinal formula BNG-1, a non-specific inhibitor of phospho-diesterases (PDEs), can be considered as a potential anti-inflammatory agent. The present study was aimed at determining the effects of BNG-1 on the development of non-alcoholic fatty liver disease (NAFLD) in mice. Desi...

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Autores principales: Guo, Chih-Hung, Chen, Wen-Long, Liao, Chung-Huei, Huang, Karin, Chen, Pei-Yin, Yang, Chun-Pai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097264/
https://www.ncbi.nlm.nih.gov/pubmed/30123057
http://dx.doi.org/10.7150/ijms.26941
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author Guo, Chih-Hung
Chen, Wen-Long
Liao, Chung-Huei
Huang, Karin
Chen, Pei-Yin
Yang, Chun-Pai
author_facet Guo, Chih-Hung
Chen, Wen-Long
Liao, Chung-Huei
Huang, Karin
Chen, Pei-Yin
Yang, Chun-Pai
author_sort Guo, Chih-Hung
collection PubMed
description Background: Chinese medicinal formula BNG-1, a non-specific inhibitor of phospho-diesterases (PDEs), can be considered as a potential anti-inflammatory agent. The present study was aimed at determining the effects of BNG-1 on the development of non-alcoholic fatty liver disease (NAFLD) in mice. Design and Methods: Male CD1 mice were randomly divided into seven groups, the control Con (4) and Con (8)+saline groups were fed a standard control diet for four or eight weeks; the experimental HFD (4) and HFD (8)+saline groups were fed a high fat diet for four or eight weeks; the HFD (8)+LBNG, HFD (8)+MBNG, and HFD (8)+HBNG groups received a high fat diet along with low, moderate or high doses of BNG-1 (0.026, 0.035, and 0.052g/30g body weight) which was administered for the last four weeks of an eight-week experimental period. After the end of experiment, blood and tissue samples were taken and analyzed. Results: Mice in the HFD (4) group had higher levels of alanine aminotransferase (ALT), plasma and hepatic triglyceride and cholesterol, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) compared with mice in the Con (4) group. Mice receiving the high fat diet along with the BNG-1 supplement had decreased body weight gains and lower visceral fat weights compared with the HFD (8)+saline group. They had also significantly reduced levels of abnormal ALT and HOMA-IR, and improved blood lipid profile. BNG-1-treated mice exhibited reduced hepatic lipid accumulation, lower oxidative stress, and decreased expression of pro-inflammatory cytokines (TNF-α and IL-1β). Furthermore, BNG-1 treatment resulted in down-regulation of hepatic cyclic-AMP dependent PDE3B and up-regulation of PDE3B expression in epididymis adipose tissue. Conclusions: BNG-1 mediated changes in PDE3B expression along with reduction in oxidative stress and inflammation. BNG-1 may ameliorate insulin resistance and hepatic steatosis in the NAFLD mouse model.
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spelling pubmed-60972642018-08-17 Effects of Chinese Medicinal Formula BNG-1 on Phosphodiesterase 3B Expression, Hepatic Steatosis, and Insulin Resistance in High Fat Diet-induced NAFLD Mice Guo, Chih-Hung Chen, Wen-Long Liao, Chung-Huei Huang, Karin Chen, Pei-Yin Yang, Chun-Pai Int J Med Sci Research Paper Background: Chinese medicinal formula BNG-1, a non-specific inhibitor of phospho-diesterases (PDEs), can be considered as a potential anti-inflammatory agent. The present study was aimed at determining the effects of BNG-1 on the development of non-alcoholic fatty liver disease (NAFLD) in mice. Design and Methods: Male CD1 mice were randomly divided into seven groups, the control Con (4) and Con (8)+saline groups were fed a standard control diet for four or eight weeks; the experimental HFD (4) and HFD (8)+saline groups were fed a high fat diet for four or eight weeks; the HFD (8)+LBNG, HFD (8)+MBNG, and HFD (8)+HBNG groups received a high fat diet along with low, moderate or high doses of BNG-1 (0.026, 0.035, and 0.052g/30g body weight) which was administered for the last four weeks of an eight-week experimental period. After the end of experiment, blood and tissue samples were taken and analyzed. Results: Mice in the HFD (4) group had higher levels of alanine aminotransferase (ALT), plasma and hepatic triglyceride and cholesterol, and homeostasis model assessment-estimated insulin resistance (HOMA-IR) compared with mice in the Con (4) group. Mice receiving the high fat diet along with the BNG-1 supplement had decreased body weight gains and lower visceral fat weights compared with the HFD (8)+saline group. They had also significantly reduced levels of abnormal ALT and HOMA-IR, and improved blood lipid profile. BNG-1-treated mice exhibited reduced hepatic lipid accumulation, lower oxidative stress, and decreased expression of pro-inflammatory cytokines (TNF-α and IL-1β). Furthermore, BNG-1 treatment resulted in down-regulation of hepatic cyclic-AMP dependent PDE3B and up-regulation of PDE3B expression in epididymis adipose tissue. Conclusions: BNG-1 mediated changes in PDE3B expression along with reduction in oxidative stress and inflammation. BNG-1 may ameliorate insulin resistance and hepatic steatosis in the NAFLD mouse model. Ivyspring International Publisher 2018-07-30 /pmc/articles/PMC6097264/ /pubmed/30123057 http://dx.doi.org/10.7150/ijms.26941 Text en © Ivyspring International Publisher This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
spellingShingle Research Paper
Guo, Chih-Hung
Chen, Wen-Long
Liao, Chung-Huei
Huang, Karin
Chen, Pei-Yin
Yang, Chun-Pai
Effects of Chinese Medicinal Formula BNG-1 on Phosphodiesterase 3B Expression, Hepatic Steatosis, and Insulin Resistance in High Fat Diet-induced NAFLD Mice
title Effects of Chinese Medicinal Formula BNG-1 on Phosphodiesterase 3B Expression, Hepatic Steatosis, and Insulin Resistance in High Fat Diet-induced NAFLD Mice
title_full Effects of Chinese Medicinal Formula BNG-1 on Phosphodiesterase 3B Expression, Hepatic Steatosis, and Insulin Resistance in High Fat Diet-induced NAFLD Mice
title_fullStr Effects of Chinese Medicinal Formula BNG-1 on Phosphodiesterase 3B Expression, Hepatic Steatosis, and Insulin Resistance in High Fat Diet-induced NAFLD Mice
title_full_unstemmed Effects of Chinese Medicinal Formula BNG-1 on Phosphodiesterase 3B Expression, Hepatic Steatosis, and Insulin Resistance in High Fat Diet-induced NAFLD Mice
title_short Effects of Chinese Medicinal Formula BNG-1 on Phosphodiesterase 3B Expression, Hepatic Steatosis, and Insulin Resistance in High Fat Diet-induced NAFLD Mice
title_sort effects of chinese medicinal formula bng-1 on phosphodiesterase 3b expression, hepatic steatosis, and insulin resistance in high fat diet-induced nafld mice
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097264/
https://www.ncbi.nlm.nih.gov/pubmed/30123057
http://dx.doi.org/10.7150/ijms.26941
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