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Quercetin prevents alcohol-induced liver injury through targeting of PI3K/Akt/nuclear factor-κB and STAT3 signaling
Minglin Zhu1, Xuefeng Zhou1, Jinping Zhao1
1Department of Thoracic and Cardiovascular Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
Abstract:
Quercetin is a type of flavonoid compound, which has potent antioxidant and anti-inflammatory activities, capable of treating a variety of diseases including neurodegenerative diseases, tumors, diabetes and obesity. The present study selected alcohol-induced liver injury model mice and aimed at studying the protective role of quercetin in preventing alcohol-induced liver injury. In alcohol-induced liver injury mice treated with quercetin, it was demonstrated that levels of aspartate transaminase, alanine transaminase, total bilirubin and triglyceride were reduced. In addition to this, the activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase were increased, malondialdehyde was inhibited, and interleukin (IL)-1β, IL-6, IL-10 and inducible nitric oxide synthase were suppressed. Quercetin additionally suppressed the protein expression levels of B-cell lymphoma (Bcl)-2, Bcl-2 associated X apoptosis regulator, Caspase-3, poly ADP-ribose polymerase, and signal transducer and activator of transcription (STAT) 3 phosphorylation, nuclear factor (NF)-κB and protein kinase B (Akt) phosphorylation levels in alcohol-induced liver injured mice. These results suggested that the protective role of quercetin prevents alcohol-induced liver injury through the phosphoinositide 3-kinase/Akt/NF-κB and STAT3 pathway.
Insights
Quercetin, a flavonoid, protects the liver from alcohol-induced injury by reducing harmful biomarkers and boosting antioxidant enzymes. It also modulates key signaling pathways involved in inflammation and cell death.
Area of Science:
- Biochemistry
- Pharmacology
- Hepatology
Background:
- Quercetin is a flavonoid with known antioxidant and anti-inflammatory properties.
- Alcohol-induced liver injury (AILI) is a significant health concern with limited therapeutic options.
- Flavonoids like quercetin show potential in managing various diseases, including liver conditions.
Purpose of the Study:
- To investigate the protective effects of quercetin against alcohol-induced liver injury in a mouse model.
- To elucidate the molecular mechanisms underlying quercetin's hepatoprotective action.
Main Methods:
- Establishment of an alcohol-induced liver injury mouse model.
- Administration of quercetin to AILI mice.
- Biochemical analysis of liver enzymes (AST, ALT), bilirubin, and triglyceride levels.
- Measurement of antioxidant enzyme activities (SOD, GPx) and malondialdehyde (MDA) levels.
- Assessment of inflammatory cytokine (IL-1β, IL-6, IL-10) and iNOS levels.
- Evaluation of apoptosis-related protein expression (Bcl-2, Bax, Caspase-3, PARP) and signaling pathway activation (STAT3, NF-κB, Akt phosphorylation).
Main Results:
- Quercetin treatment significantly reduced liver enzymes (AST, ALT), total bilirubin, and triglyceride levels in AILI mice.
- Quercetin increased the activities of antioxidant enzymes (SOD, GPx) and inhibited MDA levels.
- Quercetin suppressed the expression of pro-inflammatory cytokines (IL-1β, IL-6, iNOS) and modulated IL-10 levels.
- Quercetin inhibited apoptosis by downregulating Bcl-2, Bax, Caspase-3, and PARP expression.
- Quercetin reduced the phosphorylation of STAT3, NF-κB, and Akt signaling pathways.
Conclusions:
- Quercetin demonstrates significant hepatoprotective effects against alcohol-induced liver injury.
- The protective mechanisms involve antioxidant, anti-inflammatory, and anti-apoptotic activities.
- Quercetin exerts its effects by modulating the PI3K/Akt/NF-κB and STAT3 signaling pathways.
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