Sugarcane Molasses Polyphenol Extract Attenuates Alcohol-Induced Chronic Liver Damage via Antioxidant, Anti-Inflammatory, and CYP2E1/Keap1/NF-κB Pathway Modulation

Background/Objective: The prevention and treatment of alcoholic liver disease (ALD) urgently require safe and effective nutritional intervention strategies. Polyphenol extracts from sugarcane molasses (SP) show antioxidant and anti-inflammatory potential, yet their protective effects against ALD have not been elucidated. This study explored the therapeutic potential of SP in alcohol-induced chronic liver damage. Methods: A graded alcohol concentration-induced liver damage model was established in C57BL/6J mice to systematically evaluate SP’s regulatory effects on liver function markers, lipid metabolism, oxidative stress indicators, inflammatory factors, and related molecular mechanisms through a 10-week nutritional intervention. Results: The results demonstrated that SP intervention significantly inhibited the liver index, alanine aminotransferase and aspartate aminotransferase activities, and triglyceride and total cholesterol accumulation in mice. SP enhanced antioxidant enzyme activities in a dose-dependent manner, with the high-dose group increasing catalase activity by 161.19% and superoxide dismutase activity by 22.97%. Furthermore, SP significantly reduced the levels of pro-inflammatory cytokines, including interleukin-1β, interleukin-6, and tumor necrosis factor-α, thereby alleviating hepatic inflammatory infiltration. Mechanistic studies revealed that SP effectively mitigated alcohol-induced oxidative stress and inflammatory injury by inhibiting cytochrome P450 2E1 overexpression, regulating the Kelch-like ECH-associated protein 1 signaling pathway, and suppressing nuclear factor-kappa B pathway activation. Conclusions: The findings reveal that SP mitigates ALD via synergistic antioxidant and anti-inflammatory mechanisms, providing a novel strategy for high-value utilization of sugarcane molasses byproducts in agricultural industries. Future studies should focus on the contribution of the different phenolics in SP and validate their specific hepatoprotective mechanisms.