期刊
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
卷 67, 期 5, 页码 1392-1401出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.8b05943
关键词
maltol; thioacetamide; hepatic fibrosis; PI3K/Akt signaling pathway; apoptosis
资金
- National Natural Science Foundation of China [31770378]
- Jilin Science & Technology Development Plan [20180201083YY, 20191102051YY, 20190103092JH, 20190304003YY]
- Scientific Research Foundation for the Returned Overseas Chinese Scholars (Jilin Province, 2015)
- Program for the Young Top-notch and Innovative Talents of Jilin Agricultural University (2016-2018)
Our previous study has confirmed that maltol can attenuate alcohol-induced acute hepatic damage and prevent oxidative stress in mice. Therefore, maltol might have the capacity to improve thioacetamide (TAA)-induced liver fibrosis. The purpose of this work was to explore the antifibrotic efficacy and underlying mechanisms of maltol for TAA-treated mice. Progressive liver fibrosis was established with a dose-escalating protocol in which the mice received TAA intraperitoneal three times a week for a total duration of 9 weeks. The injection doses of TAA were 50 mg/kg for the first week, 100 mg/kg for the second and third weeks, and 150 mg/kg for the rest of the injections. Maltol with doses of 50 and 100 mg/kg was given by gavage after 4 weeks of intraperitoneal injection of TAA, respectively, once daily for 5 weeks. Results indicated that TAA intraperitoneal injection significantly increased serum activities of alanine aminotransferase (ALT) (52.93 +/- 13.21 U/L vs 10.22 +/- 3.36 U/L) and aspartate aminotransferase (AST) (67.58 +/- 25.84 U/L vs 39.34 +/- 3.89 U/L); these elevations were significantly diminished by pretreatment with maltol. Additionally, maltol ameliorated TAA-induced oxidative stress with attenuation in MDA (p < 0.05 or p < 0.01) content; evident elevation in the GSH levels, GSH/GSSG ratio (p < 0.05 or p < 0.01), and superoxide dismutase (SOD) (p < 0.01); and restored liver histology accompanied by a decrease of alpha-smooth muscle actin (alpha-SMA) expression. Furthermore, maltol significantly suppressed the transforming growth factor-beta 1 (TGF-beta 1) expression and the PI3K/Akt pathway. This study suggested that maltol alleviated experimental liver fibrosis by suppressing the activation of HSCs and inducing apoptosis of activated HSCs through TGF-beta 1-mediated PI3K/Akt signaling pathway. These findings further clearly suggested that maltol is a potent therapeutic candidate for the alleviation of liver fibrosis.
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