Prickly pear (Rosa roxburghii Tratt.) extract alleviates ethanol-induced oxidative stress in vivo and in vitro via Fanconi Anemia pathway

Prickly pear extract (PPE) exhibits diverse effects, including antioxidative, hypoglycemic, and antiobesity properties. While its role in alcoholic liver disease (ALD) prevention remains understudied, this research unveils PPE's chemical composition (total protein, sugar, phenols, flavonoids, and polyphenols). Employing an ALD animal model, we identified 12 PPE metabolites that directly entered the liver, mitigating alcohol-induced oxidative damage by reducing ALT, AST, and MDA levels, elevating SOD and GSH levels, and enhancing ADH and ALDH enzymatic activity. Examining ethanol-induced HepG2 cells, PPE activated the Fanconi anemia (FA) pathway, upregulating proteins (ub-FANCD2, ub-FANCI, FANCA) involved in antioxidant gene expression and FA complex proteins (ub-FANCM, MHF1, FAAP24) promoting DNA repair. These findings highlight PPE's ability to combat oxidative stress and DNA damage through FA pathway activation, affirming its hepatoprotective potential as a natural product. • The antioxidant activity of Prickly pear extract (PPE) was determined. • The metabolism profile of PPE was determined. • 12 PPE-enriched metabolites enter liver directly. • PPE inhibits alcoholic liver injury by activating FA pathway.