Pear Peel–Enriched Residue Extract Attenuates Ethanol‐Induced Liver Injury Through Regulation of Antioxidant Signaling and Lipid Metabolism

Excessive alcohol consumption induces progressive liver injury through oxidative stress, lipid accumulation, and inflammation, primarily driven by dysregulated ethanol (EtOH) metabolism. Given the growing interest in plant‐derived phytochemicals for hepatoprotection, pear ( Pyrus pyrifolia ) has attracted attention due to its antioxidant and lipid‐regulating properties; however, the bioactive fractions and mechanisms underlying the hepatoprotective effects of pear peel–enriched residue extracts (PPE) remain unclear. Therefore, we evaluated the hepatoprotective potential of PPE against EtOH‐induced liver injury using in vitro, in vivo, and in silico approaches. In HepG2 cells, PPE reduced oxidative stress, restored cell viability, and reduced intracellular EtOH and acetaldehyde levels more effectively than pear extract, with efficacy comparable to silymarin. In EtOH‐treated C57BL/6 mice, PPE attenuated liver injury markers, reduced hepatic lipid accumulation, and improved histopathological alterations. PPE also modulated the expression of proteins associated with oxidative stress and lipid metabolism. GNPS–FBMN analysis putatively annotated over 120 phytochemicals (or metabolites), and in silico analyses suggested potential interactions between selected metabolites and proteins involved in EtOH metabolism and lipid regulation. These findings suggest that PPE shows hepatoprotective potential and warrants further investigation as a potential candidate for the mitigation of alcohol‐associated liver disease.