Puerarin Ameliorates Experimental Alcoholic Liver Injury by Inhibition of Endotoxin Gut Leakage, Kupffer Cell Activation, and Endotoxin Receptors Expression

Puerarin is an isoflavone component extracted from Kudzu (Pueraria lobata) and has been demonstrated to alleviate alcohol-related disorder. The purpose of this study was to examine whether puerarin ameliorates chronic alcoholic liver injury through inhibition of endotxin gut-leakage, the subsequent Kupffer cells (KCs) activation and lipopolysaccharide (LPS) receptors expression. Rats were provided with the Liber-DeCarli liquid diet for eight weeks. Puerarin (90 mg and 180 mg/kg.d) was orally administered from the beginning of the third week till the end of the experiment. Chronic alcohol intake caused increased serum ALT, AST, hepatic GGT and TG levels as well as fatty liver and neutrophil infiltration in hepatic lobules determined by biochemical and histological assay. A significant increase of liver tumor necrosis factor α (TNF-α) was detected by enzyme-linked immunosorbent assay. These pathological effects correlated with increased endotoxin level in portal vein and up-regulated protein expression of hepatic CD68, LBP, CD14, TLR2 and TLR4. Meanwhile, the intestinal microvilli were observed to be sparse, shortened and irregularity in distribution under the transmission electron microscope in conjunction with the down-regulated intestinal ZO-1 protein expression. These hepatic pathological changes were significantly inhibited in puerarin-treated animals, as well as the endotoxin level, hepatic CD68 and LPS receptors. Morevore, the pathological changes in intestinal microvillus and decreased intestinal ZO-1 were also ameliorated with puerarin treatment. These results thus demonstrate that puerarin inhibition of endotoxin gut-leakage, KCs activation and LPS receptors expression is importantly involved in the alleviation of chronic alcoholic liver injury in rats.