This study investigates the protective effects and mechanisms of glucosamine (GLC) on alcohol-induced acute liver injury in both in vivo and in vitro models. GLC, a commonly used supplement for osteoarthritis, has anti-inflammatory and antioxidant properties. The research was conducted using mouse models and human normal hepatocyte L02 cells. Key findings include: 1. **Protective Effects on Liver Cells**: - GLC significantly improved cell survival rates and reduced liver cell damage in both L02 cells and mice. - It reduced serum markers of liver injury such as ALT, AST, ALP, and LDH. 2. **Oxidative Stress Reduction**: - GLC decreased lipid peroxidation markers (MDA) and increased antioxidant enzymes (GSH, SOD, CAT) in L02 cells and mouse liver. - It also reduced the expression of CYP2E1, an ethanol-metabolizing enzyme, which is crucial for maintaining redox balance. 3. **Lipid Metabolism Improvement**: - GLC improved serum lipid metabolism by reducing levels of TG, VLDL, and LDL-C and increasing HDL-C in mice. 4. **Inflammatory Response Modulation**: - GLC reduced the expression of inflammatory factors (TNF-α, IL-1β, IL-6) and inhibited the activation of MAPK and NF-κB signaling pathways, thereby alleviating inflammation. 5. **Mechanisms of Action**: - GLC activated the Keap1/Nrf2/HO-1 antioxidant pathway, enhancing the liver's antioxidant capacity. - It inhibited the phosphorylation of JNK and p38 MAPK, reducing inflammation and cell apoptosis. 6. **Conclusion**: - GLC shows potential as a dietary supplement for treating alcohol-induced acute liver injury by mitigating oxidative stress and inflammation. Further research is needed to explore specific lipid metabolism mechanisms, intestinal histopathology, and the NF-κB pathway in more detail. This study provides a theoretical foundation for the development of GLC as a functional food to prevent and treat alcoholic liver disease.This study investigates the protective effects and mechanisms of glucosamine (GLC) on alcohol-induced acute liver injury in both in vivo and in vitro models. GLC, a commonly used supplement for osteoarthritis, has anti-inflammatory and antioxidant properties. The research was conducted using mouse models and human normal hepatocyte L02 cells. Key findings include: 1. **Protective Effects on Liver Cells**: - GLC significantly improved cell survival rates and reduced liver cell damage in both L02 cells and mice. - It reduced serum markers of liver injury such as ALT, AST, ALP, and LDH. 2. **Oxidative Stress Reduction**: - GLC decreased lipid peroxidation markers (MDA) and increased antioxidant enzymes (GSH, SOD, CAT) in L02 cells and mouse liver. - It also reduced the expression of CYP2E1, an ethanol-metabolizing enzyme, which is crucial for maintaining redox balance. 3. **Lipid Metabolism Improvement**: - GLC improved serum lipid metabolism by reducing levels of TG, VLDL, and LDL-C and increasing HDL-C in mice. 4. **Inflammatory Response Modulation**: - GLC reduced the expression of inflammatory factors (TNF-α, IL-1β, IL-6) and inhibited the activation of MAPK and NF-κB signaling pathways, thereby alleviating inflammation. 5. **Mechanisms of Action**: - GLC activated the Keap1/Nrf2/HO-1 antioxidant pathway, enhancing the liver's antioxidant capacity. - It inhibited the phosphorylation of JNK and p38 MAPK, reducing inflammation and cell apoptosis. 6. **Conclusion**: - GLC shows potential as a dietary supplement for treating alcohol-induced acute liver injury by mitigating oxidative stress and inflammation. Further research is needed to explore specific lipid metabolism mechanisms, intestinal histopathology, and the NF-κB pathway in more detail. This study provides a theoretical foundation for the development of GLC as a functional food to prevent and treat alcoholic liver disease.