<b><i>Background:</i></b> Puerarin (PR) as one of the main ingredients of the root of the traditional herb Kudzu has been suggested to improve chronic alcohol-induced liver injury. We explore the specific mechanisms of PR on hepatocellular changes after administration of alcohol. <b><i>Methods:</i></b> Sprague-Dawley rats were treated with 55% alcohol for 12 weeks to induce a chronic alcoholic liver damage model. Then the rats in each group were administered by oral gavage with zileuton, celecoxib, and PR for 2 weeks, respectively. <b><i>Results:</i></b> In the PR group, the weight loss was markedly improved and the abnormal serum alanine aminotransferase and aspartate aminotransferase were significantly lowered after PR treatment when compared to the alcoholic liver injured model group. Pathological examination indicated that alcohol-induced hepatocellular injury was improved by the PR treatment. The 5-lipoxygenase (5-Lox) and cyclooxygenase-2 (Cox-2) at the protein level and the mRNA level were obviously downregulated accompanied with the PR treatment. Meanwhile, the peroxisome proliferator-activated receptor γ (PPAR-γ) at the protein and mRNA level was notably elevated and the tumor necrosis factor α at the protein and mRNA level was markedly decreased following the PR treatment. <b><i>Conclusion:</i></b> The possible cytoprotective mechanisms of PR may be involved inhibition of the Cox-2 pathway and the 5-Lox pathway to suppress inflammatory response and regulate the protective factor PPAR-γ expression.
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