title: Puerarin ameliorates experimental alcoholic liver injury by inhibition of endotoxin gut leakage, Kupffer cell activation, and endotoxin receptors expression.
abstract: Puerarin, an isoflavone component extracted from Kudzu (Pueraria lobata), has been demonstrated to alleviate alcohol-related disorders. Our study examined whether puerarin ameliorates chronic alcoholic liver injury through inhibition of endotoxin gut leakage, the subsequent Kupffer cell activation, and endotoxin receptors expression. Rats were provided with the Liber-DeCarli liquid diet for 8 weeks. Puerarin (90 mg/kg or 180 mg/kg daily) was orally administered from the beginning of the third week until the end of the experiment. Chronic alcohol intake caused increased serum alanine aminotransferase, aspartate aminotransferase, hepatic gamma-glutamyl transpeptidase, and triglyceride levels as well as fatty liver and neutrophil infiltration in hepatic lobules as determined by biochemical and histologic assays. A significant increase of liver tumor necrosis factor α was detected by enzyme-linked immunosorbent assay. These pathologic effects correlated with increased endotoxin level in portal vein and upregulated protein expression of hepatic CD68, lipopolysaccharide-binding protein, CD14, Toll-like receptor 2, and Toll-like receptor 4. Meanwhile, the intestinal microvilli were observed to be sparse, shortened, and irregularity in distribution under the transmission electron microscope in conjunction with the downregulated intestinal zonula occludens-1 protein expression. These hepatic pathologic changes were significantly inhibited in puerarin-treated animals as were the endotoxin levels and hepatic CD68 and endotoxin receptors. Moreover, the pathologic changes in intestinal microvillus and the decreased intestinal zonula occludens-1 were also ameliorated with puerarin treatment. These results thus demonstrate that puerarin inhibition of endotoxin gut leakage, Kupffer cell activation, and endotoxin receptors expression is involved in the alleviation of chronic alcoholic liver injury in rats.
authors.affiliation: Institute of Liver Diseases, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Zhangheng Road, Pudong District, Shanghai, 201203, People's Republic of China.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Peng
authors.forename: Tuan
authors.initials: T
authors.lastname: Cui
authors.forename: Fu
authors.initials: F
authors.lastname: Huang
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Lin
authors.initials: L
authors.lastname: Xu
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Xu
authors.forename: Qin
authors.initials: Q
authors.lastname: Feng
authors.forename: Yi-Yang
authors.initials: YY
authors.lastname: Hu
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D000410:Alanine Transaminase / Q000097:blood; D019973:Alcohol-Related Disorders / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D001219:Aspartate Aminotransferases / Q000097:blood; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D004032:Diet; D004195:Disease Models, Animal; D004731:Endotoxins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005234:Fatty Liver / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects; D007529:Isoflavones / Q000494:pharmacology*; D007728:Kupffer Cells / Q000187:drug effects* / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008871:Microvilli / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000235:genetics; D011169:Portal Vein / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D062826:Zonula Occludens-1 Protein / Q000235:genetics / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000378:metabolism; D000099231:Lipopolysaccharide-Binding Protein; D000097382:CD68 Molecule
chemical_list: D000209:Acute-Phase Proteins; D000410:Alanine Transaminase; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001219:Aspartate Aminotransferases; D002352:Carrier Proteins; D004731:Endotoxins; D007529:Isoflavones; D018950:Lipopolysaccharide Receptors; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D005723:gamma-Glutamyltransferase; D000099231:Lipopolysaccharide-Binding Protein; C539355:CD68 protein, rat; D000097382:CD68 Molecule; C569044:Tjp1 protein, rat; C048071:endotoxin receptor; C033607:puerarin