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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

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

Jing-Hua Peng, Tuan Cui, Fu Huang, Liang Chen, Yu Zhao, Lin Xu, Li-Li Xu, Qin Feng and Yi-Yang Hu
Journal of Pharmacology and Experimental Therapeutics March 2013, 344 (3) 646-654; DOI: https://doi.org/10.1124/jpet.112.201137
Jing-Hua Peng
Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai (J.-H.P., T.C., F.H., L.C., Y.Z., L.X., L.-L.X., Q.F., Y.-Y.H.); Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional Chinese Medicine, Ministry of Education, Shanghai (J.-H.P., T.C., F.H., L.C., Y.Z., L.X., L.-L.X., Q.F., Y.-Y.H.); Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai (J.-H.P., Y.-Y.H.); and E-Institute of TCM Internal Medicine, Shanghai Municipal Education Commission, Shanghai (Y.-Y.H.), People’s Republic of China
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Tuan Cui
Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai (J.-H.P., T.C., F.H., L.C., Y.Z., L.X., L.-L.X., Q.F., Y.-Y.H.); Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional Chinese Medicine, Ministry of Education, Shanghai (J.-H.P., T.C., F.H., L.C., Y.Z., L.X., L.-L.X., Q.F., Y.-Y.H.); Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai (J.-H.P., Y.-Y.H.); and E-Institute of TCM Internal Medicine, Shanghai Municipal Education Commission, Shanghai (Y.-Y.H.), People’s Republic of China
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Fu Huang
Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai (J.-H.P., T.C., F.H., L.C., Y.Z., L.X., L.-L.X., Q.F., Y.-Y.H.); Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional Chinese Medicine, Ministry of Education, Shanghai (J.-H.P., T.C., F.H., L.C., Y.Z., L.X., L.-L.X., Q.F., Y.-Y.H.); Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai (J.-H.P., Y.-Y.H.); and E-Institute of TCM Internal Medicine, Shanghai Municipal Education Commission, Shanghai (Y.-Y.H.), People’s Republic of China
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Liang Chen
Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai (J.-H.P., T.C., F.H., L.C., Y.Z., L.X., L.-L.X., Q.F., Y.-Y.H.); Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional Chinese Medicine, Ministry of Education, Shanghai (J.-H.P., T.C., F.H., L.C., Y.Z., L.X., L.-L.X., Q.F., Y.-Y.H.); Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai (J.-H.P., Y.-Y.H.); and E-Institute of TCM Internal Medicine, Shanghai Municipal Education Commission, Shanghai (Y.-Y.H.), People’s Republic of China
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Yu Zhao
Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai (J.-H.P., T.C., F.H., L.C., Y.Z., L.X., L.-L.X., Q.F., Y.-Y.H.); Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional Chinese Medicine, Ministry of Education, Shanghai (J.-H.P., T.C., F.H., L.C., Y.Z., L.X., L.-L.X., Q.F., Y.-Y.H.); Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai (J.-H.P., Y.-Y.H.); and E-Institute of TCM Internal Medicine, Shanghai Municipal Education Commission, Shanghai (Y.-Y.H.), People’s Republic of China
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Lin Xu
Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai (J.-H.P., T.C., F.H., L.C., Y.Z., L.X., L.-L.X., Q.F., Y.-Y.H.); Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional Chinese Medicine, Ministry of Education, Shanghai (J.-H.P., T.C., F.H., L.C., Y.Z., L.X., L.-L.X., Q.F., Y.-Y.H.); Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai (J.-H.P., Y.-Y.H.); and E-Institute of TCM Internal Medicine, Shanghai Municipal Education Commission, Shanghai (Y.-Y.H.), People’s Republic of China
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Li-Li Xu
Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai (J.-H.P., T.C., F.H., L.C., Y.Z., L.X., L.-L.X., Q.F., Y.-Y.H.); Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional Chinese Medicine, Ministry of Education, Shanghai (J.-H.P., T.C., F.H., L.C., Y.Z., L.X., L.-L.X., Q.F., Y.-Y.H.); Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai (J.-H.P., Y.-Y.H.); and E-Institute of TCM Internal Medicine, Shanghai Municipal Education Commission, Shanghai (Y.-Y.H.), People’s Republic of China
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Qin Feng
Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai (J.-H.P., T.C., F.H., L.C., Y.Z., L.X., L.-L.X., Q.F., Y.-Y.H.); Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional Chinese Medicine, Ministry of Education, Shanghai (J.-H.P., T.C., F.H., L.C., Y.Z., L.X., L.-L.X., Q.F., Y.-Y.H.); Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai (J.-H.P., Y.-Y.H.); and E-Institute of TCM Internal Medicine, Shanghai Municipal Education Commission, Shanghai (Y.-Y.H.), People’s Republic of China
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Yi-Yang Hu
Institute of Liver Diseases, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai (J.-H.P., T.C., F.H., L.C., Y.Z., L.X., L.-L.X., Q.F., Y.-Y.H.); Key Laboratory of Liver and Kidney Diseases, Shanghai University of Traditional Chinese Medicine, Ministry of Education, Shanghai (J.-H.P., T.C., F.H., L.C., Y.Z., L.X., L.-L.X., Q.F., Y.-Y.H.); Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai (J.-H.P., Y.-Y.H.); and E-Institute of TCM Internal Medicine, Shanghai Municipal Education Commission, Shanghai (Y.-Y.H.), People’s Republic of China
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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.

Footnotes

  • This work was supported by the National Natural Science Foundation of China [No. 81001575]; the Leading Academic Discipline of Hepatology of State Administration of TCM China [No. 2010sh]; and the Innovative Research Team in Shanghai Universities, Shanghai Municipal Education Commission.

  • dx.doi.org/10.1124/jpet.112.201137.

  • ↵Embedded ImageThis article has supplemental material available at jpet.aspetjournals.org.

  • Received October 15, 2012.
  • Accepted December 27, 2012.
  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 344 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 344, Issue 3
1 Mar 2013
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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Inhibition of Endotoxin Signaling Pathway by Puerarin in ALD

Jing-Hua Peng, Tuan Cui, Fu Huang, Liang Chen, Yu Zhao, Lin Xu, Li-Li Xu, Qin Feng and Yi-Yang Hu
Journal of Pharmacology and Experimental Therapeutics March 1, 2013, 344 (3) 646-654; DOI: https://doi.org/10.1124/jpet.112.201137

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Research ArticleGastrointestinal, Hepatic, Pulmonary, and Renal

Inhibition of Endotoxin Signaling Pathway by Puerarin in ALD

Jing-Hua Peng, Tuan Cui, Fu Huang, Liang Chen, Yu Zhao, Lin Xu, Li-Li Xu, Qin Feng and Yi-Yang Hu
Journal of Pharmacology and Experimental Therapeutics March 1, 2013, 344 (3) 646-654; DOI: https://doi.org/10.1124/jpet.112.201137
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