Astaxanthin alleviated ethanol-induced liver injury by inhibition of oxidative stress and inflammatory responses via blocking of STAT3 activity

Abstract

Astaxanthin (AXT) is classified as a xanthophyll carotenoid compound which have broader functions including potent antioxidant, anti-inflammatory and neuroprotective properties. Considerable researches have demonstrated that AXT shows preventive and therapeutic properties against for Diabetes, Osteoarthritis and Rheumatoid Arthritis. However, the protective effect of AXT on liver disease has not yet been reported. In this study, we investigated effects of AXT on ethanol-induced liver injury in chronic plus binge alcohol feeding model. The hepatic steatosis and inflammation induced by ethanol administration were alleviated by AXT. Serum levels of aspartate transaminase and alanine transaminase were decreased in the livers of AXT administrated group. The ethanol-induced expression of cytochrome P450 2E1 (CYP2E1), pro-inflammatory proteins, cytokines, chemokines and reactive oxygen species (ROS) levels were also reduced in the livers of AXT administrated group. Moreover, ethanol-induced infiltration of neutrophils was decreased in the livers of AXT administrated group. Docking model and pull-down assay showed that AXT directly binds to the DNA binding site of STAT3. Moreover, AXT decreased STAT3 phosphorylation in the liver of AXT administration group. Therefore, these results suggest that AXT could prevent ethanol-induced hepatic injury via inhibition of oxidant and inflammatory responses via blocking of STAT3 activity.

Protective Effects of Fucoxanthin against Alcoholic Liver Injury by Activation of Nrf2-Mediated Antioxidant Defense and Inhibition of TLR4-Mediated Inflammation

“…ALT and AST activities of Positive group and Fx group mice were significantly less than those of the Model group and gradually tended to Control group (Figure 3). These results indicate that Fx could control ALT and AST activities, thereby reducing alcohol-induced liver injury; this hypothesis is also supported by findings by Han et al [32].…”

Comparative Transcriptome Analyses Provide Potential Insights into the Molecular Mechanisms of Astaxanthin in the Protection against Alcoholic Liver Disease in Mice

“…Moreover, AST is also a potential protector against liver damage [11]. It can inhibit liver fibrosis and lipid peroxidation [17]; inhibit liver tumorigenesis and inflammation [18]; attenuate hepatic ischemia reperfusion-induced apoptosis and autophagy [19,20]; and prevent ethanol-induced hepatic injury through the in vivo inhibition of oxidant and inflammatory responses [21]. Additionally, AST possesses anti-fibrogenic effects, through the TGFβ1–Smad3 signaling pathway in hepatic stellate cells [22].…”

<p>Astaxanthin in Liver Health and Disease: A Potential Therapeutic Agent</p>

“…74 In addition, the levels of ROS, proinflammatory proteins and related inflammatory factors were also significantly decreased in liver tissue in the drug group, which may be related to negative phosphorylation of STAT3. 75 Besides inhibiting oxidative stress and inflammation to prevent alcohol-induced liver damage, astaxanthin can also regulate intestinal flora and may play a potential therapeutic role in alcoholic liver diseaseinduced bacterial diseases. 76 Similarly, liposomal encapsulation of astaxanthin exerted rapid and direct effects against repeated alcohol-induced liver disease and could boost recovery from liver injuries caused by long-term alcohol intake.…”