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Maltol Mitigates Thioacetamide-induced Liver Fibrosis through TGF-β1-mediated Activation of PI3K/Akt Signaling Pathway
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2019-01-15 00:00:00 , DOI: 10.1021/acs.jafc.8b05943 Xiao-jie Mi 1 , Jin-gang Hou 1, 2 , Shuang Jiang 1 , Zhi Liu 1 , Shan Tang 1 , Xiang-xiang Liu 1 , Ying-ping Wang 1, 3 , Chen Chen 4 , Zi Wang 1 , Wei Li 1, 3
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2019-01-15 00:00:00 , DOI: 10.1021/acs.jafc.8b05943 Xiao-jie Mi 1 , Jin-gang Hou 1, 2 , Shuang Jiang 1 , Zhi Liu 1 , Shan Tang 1 , Xiang-xiang Liu 1 , Ying-ping Wang 1, 3 , Chen Chen 4 , Zi Wang 1 , Wei Li 1, 3
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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 α-smooth muscle actin (α-SMA) expression. Furthermore, maltol significantly suppressed the transforming growth factor-β1 (TGF-β1) 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-β1-mediated PI3K/Akt signaling pathway. These findings further clearly suggested that maltol is a potent therapeutic candidate for the alleviation of liver fibrosis.
中文翻译：
麦芽酚通过TGF-β1介导的PI3K / Akt信号通路活化，减轻硫乙酰胺诱导的肝纤维化
我们以前的研究已经证实，麦芽酚可以减轻酒精引起的急性肝损伤并预防小鼠的氧化应激。因此，麦芽酚可能具有改善硫代乙酰胺（TAA）诱导的肝纤维化的能力。这项工作的目的是探讨麦芽酚对TAA治疗的小鼠的抗纤维化功效及其潜在机制。通过剂量递增方案建立渐进性肝纤维化，其中小鼠每周腹膜内接受TAA三次，总持续时间为9周。TAA的注射剂量在第一周为50 mg / kg，第二周和第三周为100 mg / kg，其余注射为150 mg / kg。分别在腹腔内注射TAA 4周后每天一次灌胃，分别给予50和100 mg / kg的麦芽酚，持续5周。结果表明TAA腹腔注射显着提高了丙氨酸转氨酶（ALT）的血清活性（52.93±13.21 U / L vs 10.22±3.36 U / L）和天冬氨酸转氨酶（AST）（67.58±25.84 U / L vs 39.34±3.89 U / L L）; 麦芽酚预处理可大大降低这些海拔。此外，麦芽酚改善了TAA诱导的氧化应激，并降低了MDA（p <0.05或p <0.01）含量; GSH水平，GSH / GSSG比（p <0.05或p <0.01）和超氧化物歧化酶（SOD）明显升高（p <0.01）；并恢复了肝脏组织学，并伴有α-平滑肌肌动蛋白（α-SMA）表达的降低。此外，麦芽酚显着抑制了转化生长因子-β1（TGF-β1）的表达和PI3K / Akt途径。这项研究表明，麦芽酚通过抑制HSC的活化并通过TGF-β1介导的PI3K / Akt信号通路诱导活化的HSC的凋亡来减轻实验性肝纤维化。这些发现进一步清楚地表明，麦芽酚是减轻肝纤维化的有效治疗候选物。
更新日期：2019-01-15
中文翻译：
麦芽酚通过TGF-β1介导的PI3K / Akt信号通路活化，减轻硫乙酰胺诱导的肝纤维化
我们以前的研究已经证实，麦芽酚可以减轻酒精引起的急性肝损伤并预防小鼠的氧化应激。因此，麦芽酚可能具有改善硫代乙酰胺（TAA）诱导的肝纤维化的能力。这项工作的目的是探讨麦芽酚对TAA治疗的小鼠的抗纤维化功效及其潜在机制。通过剂量递增方案建立渐进性肝纤维化，其中小鼠每周腹膜内接受TAA三次，总持续时间为9周。TAA的注射剂量在第一周为50 mg / kg，第二周和第三周为100 mg / kg，其余注射为150 mg / kg。分别在腹腔内注射TAA 4周后每天一次灌胃，分别给予50和100 mg / kg的麦芽酚，持续5周。结果表明TAA腹腔注射显着提高了丙氨酸转氨酶（ALT）的血清活性（52.93±13.21 U / L vs 10.22±3.36 U / L）和天冬氨酸转氨酶（AST）（67.58±25.84 U / L vs 39.34±3.89 U / L L）; 麦芽酚预处理可大大降低这些海拔。此外，麦芽酚改善了TAA诱导的氧化应激，并降低了MDA（p <0.05或p <0.01）含量; GSH水平，GSH / GSSG比（p <0.05或p <0.01）和超氧化物歧化酶（SOD）明显升高（p <0.01）；并恢复了肝脏组织学，并伴有α-平滑肌肌动蛋白（α-SMA）表达的降低。此外，麦芽酚显着抑制了转化生长因子-β1（TGF-β1）的表达和PI3K / Akt途径。这项研究表明，麦芽酚通过抑制HSC的活化并通过TGF-β1介导的PI3K / Akt信号通路诱导活化的HSC的凋亡来减轻实验性肝纤维化。这些发现进一步清楚地表明，麦芽酚是减轻肝纤维化的有效治疗候选物。
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