Oncotarget

Research Papers:

A porcine placental extract prevents steatohepatitis by suppressing activation of macrophages and stellate cells in mice

Liang Xu _, Naoto Nagata, Mayumi Nagashimada, Fen Zhuge, Yinhua Ni, Guanliang Chen, Junzo Kamei, Hiroki Ishikawa, Yasuhiko Komatsu, Shuichi Kaneko and Tsuguhito Ota

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Oncotarget. 2018; 9:15047-15060. https://doi.org/10.18632/oncotarget.24587

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Abstract

Liang Xu1, Naoto Nagata1, Mayumi Nagashimada1, Fen Zhuge1, Yinhua Ni1, Guanliang Chen1, Junzo Kamei2, Hiroki Ishikawa3, Yasuhiko Komatsu3, Shuichi Kaneko1 and Tsuguhito Ota1,4

1Department of Cell Metabolism and Nutrition, Advanced Preventive Medical Sciences Research Center, Kanazawa University, Kanazawa, Japan

2Department of Pathophysiology and Therapeutics, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Tokyo, Japan

3Snowden Co., Ltd, Tokyo, Japan

4Division of Metabolism and Biosystemic Science, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan

Correspondence to:

Tsuguhito Ota, email: ota@asahikawa-med.ac.jp

Keywords: placental extract; steatohepatitis; macrophage polarization; inflammation; oxidative stress

Received: November 27, 2017     Accepted: February 21, 2018     Epub: February 27, 2018     Published: March 13, 2018

ABSTRACT

Nonalcoholic fatty liver disease (NAFLD) is caused by ectopic fat accumulation in the liver. NAFLD is associated with hepatic inflammation and oxidative stress, resulting in nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Placental extracts have been used to treat various chronic diseases due to their antioxidative effect. However, the effects of the extracts on the development of NASH have yet to be elucidated. Here, we demonstrated that supplementation with an oral porcine placental extract (PPE) attenuated lipid accumulation and peroxidation, insulin resistance, inflammatory and stress signaling, and fibrogenesis in the liver of NASH model mice fed a high-cholesterol and high-fat diet. The PPE reduced the number of M1-like liver macrophages, but increased the number of anti-inflammatory M2-like macrophages, resulting in a predominance of M2 over M1 macrophage populations in the liver of NASH mice. Accordingly, the PPE suppressed lipopolysaccharide-induced M1 polarization in isolated murine peritoneal macrophages, whereas it facilitated interleukin 4-induced M2 polarization. Furthermore, the PPE reduced the hepatic stellate cell (HSC) activation associated with the attenuated transforming growth factor-β/Smad3 signaling, both in the liver of NASH mice and in RI-T cells, a HSC line. The PPE may be a potential approach to prevent NASH by limiting lipid peroxidation, promoting M2 macrophage polarization, and attenuating HSC activation.


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