Alcoholic liver diseases has been known to be one of the major health risks worldwide. The purpose of this study was aimed to demonstrate the relative protective effect of quercetin, quercetin‐3‐glucoside, and rutin on alcohol‐induced damage in hepatocytes. The hepatotoxicity, antioxidant enzymatic defense mechanisms, and pro‐inflammatory mediators were examined for evaluating the hepatoprotective effects of quercetins in hepG2 cells. The results revealed that quercetin and its glucoside derivatives significantly prevented ethanol‐induced hepatotoxicity by decreasing hepatic aminotransferase activities and inflammatory response in HepG2 cells. Moreover, the quercetins significantly induced detoxifying enzymes via the nuclear accumulation of the NF‐E2‐related factor 2 (Nrf2) and induction of antioxidant response element (ARE) gene. These hepatoprotective activities were observed to be more effective with quercetin aglycone than quercetin glucosides. From the above findings, the present study imply that quercetin aglycone may have a vital function in the therapeutic and preventive strategies of alcoholic liver diseases. Practical applications Quercetin is commonly present in fruits and vegetables as aglycone and glucoside‐derived forms. In the present study, quercetin and its glycosides was shown to alleviate oxidative stress, glutathione depletion, and pro‐inflammatory cytokines in alcohol‐induced HepG2 cells via the Nrf2/ARE antioxidant pathway. Moreover, quercetin aglycone had better protective effects against alcohol‐induced liver damage in vitro, compared to its glycosylated form. The present study proposed that quercetin aglycone may be a more efficient hepatoprotective agent than its glucoside derivatives such as rutin in the amelioration of alcohol‐induced liver diseases.

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