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Effects of different therapeutic methods and typical recipes of Chinese medicine on activation of c-Jun N-terminal Kinase in Kupffer cells of rats with fatty liver disease

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Abstract

Objective

To observe the effects of different therapeutic methods and the recipes of Chinese medicine (CM) on the activation of c-Jun N-terminal kinase (JNK) in Kupffer cells of rats with fatty liver disease and to explore the mechanisms of these therapeutic methods.

Methods

By using a random number table, 98 rats were randomly divided into 7 groups: control group, model group, and 5 treatment groups, including soothing Liver (Gan) recipe group, invigorating Spleen (Pi) recipe group, dispelling dampness recipe group, promoting blood recipe group, and complex recipe group. Rats in the control group were fed with normal food and distilled water by gastric perfusion, while rats in the model group were fed with high-fat food and distilled spirits by gastric perfusion. Rats in the 5 treatment groups were fed with high-fat food and corresponding recipes by gastric perfusion. Twelve weeks later, all rats were sacrificed and liver tissues were stained for pathohistological observation. Kupffer cells were isolated from livers of rats to evaluate JNK and phospho-JNK expressions by Western blotting.

Results

The grade of hepatic steatosis was higher in the model group than the control group (P<0.05). Compared with the model group, the grade of fatty degeneration in soothing Liver recipe group and invigorating Spleen recipe group were significantly ameliorated (P<0.05). Expressions of JNK and phospho-JNK in Kupffer cells were significantly higher in the model group than those in the control group (P<0.05, P<0.01). Compared with the model group, expressions of JNK in all treatment groups decreased, especially in invigorating Spleen recipe group and promoting blood recipe group (P<0.05). Compared with the model group, expressions of phospho-JNK in all treatment groups declined significantly (P<0.01), especially in soothing Live recipe group and invigorating Spleen recipe group.

Conclusions

The high expressions of JNK and phospho-JNK in Kupffer cells might play an important role in the pathogenesis of fatty liver disease in rats. The recipes of CM, especially invigorating Spleen recipe and soothing Liver recipe, might protect liver against injury by reducing the total JNK protein content and inhibiting the activation of JNK protein in Kupffer cells of fatty liver model rats, which showed beneficial effects on fatty liver disease.

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References

  1. Mann RE, Smart RG, Govoni R. The epidemiology of alcoholic liver disease. Alcohol Res Health 2003;27:209–219.

    PubMed  Google Scholar 

  2. Harrison SA, Torgerson S, Hayashi PH. The natural history of nonalcoholic fatty liver disease: a clinical histopathological study. Am J Gastroen 2003;98:2042–2047.

    Article  Google Scholar 

  3. Pan FM, Zhang DX, Huang JR. Effects of Chaihu Shugan Powder on the index of hepatic fibrosis and type-B ultrasonic in patients with non-alcoholic fatty liver disease. Sichuan J Chin Med (Chin) 2009;27(2):66–68.

    Google Scholar 

  4. Li Z, Li YJ, Sun JM. Therapeutic effect of Shenling Baizhu Powder in treating patients with fatty liver disease. Med Industry Inform (Chin) 2006;3:293.

    Google Scholar 

  5. Jia JH. Thirty-six patients with fatty liver disease treated by Pingwei Powder. Zhejiang J Integr Tradit Chin West Med (Chin) 2000;10:178.

    Google Scholar 

  6. Zhong YM, Liu WQ. Two patients with fatty liver disease treated by Gexia Zhuyu Decoction. Shanxi J Tradit Chin Med (Chin) 2009;25:3.

    Google Scholar 

  7. Lefkowitch JH, Haythe JH, Regent N. Kupffer cell aggregation and perivenular distribution in steatohepatitis. Mod Pathol 2002;15:699–704.

    Article  PubMed  Google Scholar 

  8. Malaguarnera L, Rosa MD, Zambito AM, dell’Ombra N, Marco RD, Malaguarnera M. Potential role of chitotriosidase gene in nonalcoholic fatty liver disease evolution. Am J Gastroenterol 2006;101:2060–2069.

    Article  PubMed  CAS  Google Scholar 

  9. Tomita K, Tamiya G, Ando S, Ohsumi K, Chiyo T, Mizutani A, et al. Tumour necrosis factor alpha signalling through activation of Kupffer cells plays an essential role in liver fibrosis of non-alcoholic steatohepatitis in mice. Gut 2006;55:415–424.

    Article  PubMed  CAS  Google Scholar 

  10. Malhi H, Bronk SF, Werneburg NW, Gores GJ. Free fatty acids induce JNK-dependent hepatocyte lipoapoptosis. J Biol Chem 2006;281:12093–12101.

    Article  PubMed  CAS  Google Scholar 

  11. Barr RK, Bogoyevitch MA. The c-Jun N-terminal protein kinase family of mitogen-activated protein kinase (JNK MAPKs). Int J Biochem Cell Biol 2001;33:1047–1063.

    Article  PubMed  CAS  Google Scholar 

  12. Duan FJ. Pharmacology of traditional Chinese medical formulae. 1st ed. Shanghai: Shanghai Scientific and Technical Publishers; 1995: 178,114,130,238,197.

    Google Scholar 

  13. Yang QH, Zhou YC, Guo TM, Zhang W, Pan FM, Xia DQ, et al. Comparative study on the effect of different therapeutic methods and recipes of traditional Chinese medicine on plasma lipids in rats with fatty liver. New J Tradit Chin Med (Chin) 2004;36:74–75.

    Google Scholar 

  14. Brunt EM, Tiniakos DG. Pathology of steatohepatitis. Best Pract Res Clin Gastroen 2002;16:691–707.

    Article  Google Scholar 

  15. Shi X, Li BT, Li JS. Isolation, culture and identification of the rat liver Kupffer cells. J Med Postgraduates (Chin) 2000;13:242–246.

    Google Scholar 

  16. Zhong L, Liu F, Wang JC, Sun ZJ, Yuan QJ. Experimental study on pathogenesis of non-alcoholic steatohepatitis. Chin J Dig (Chin) 2006;26:324–326.

    CAS  Google Scholar 

  17. Park PH, Thakur V, Pritchard MT, McMullen MR, Nagy LE. Regulation of Kupffer cell activity during chronic ethanol exposure: role of adiponectin. J Gastroenterol Hepatol 2006;21:S30–S33.

    Article  PubMed  CAS  Google Scholar 

  18. Schwabe RF, Brenner DA. Mechanisms of liver injury. I. TNF-alpha-induced liver injury: role of IKK, JNK, and ROS pathways. Am J Physiol Gastrointest Liver Physiol 2006;290:583–589.

    Article  Google Scholar 

  19. Weston CR, Davis RJ. The JNK signal transduction pathway. Curr Opin Cell Biol 2007;19:142–149.

    Article  PubMed  CAS  Google Scholar 

  20. Shen J, Sakaida I, Uchida K, Terai S, Okita K. Leptin enhances TNF-alpha production via p38 and JNK MAPK in LPS-stimulated Kupffer cells. Life Sci 2005;77:1502–1515.

    Article  PubMed  CAS  Google Scholar 

  21. Solinas G, Naugler W, Galimi F, Lee MS, Karin M. Saturated fatty acids inhibit induction of insulin gene transcription by JNK-mediated phosphorylation of insulin-receptor substrates. Proc Natl Acad Sci USA 2006;103:16454–16459.

    Article  PubMed  CAS  Google Scholar 

  22. Tuncman G, Hirosumi J, Solinas G, Chang L, Karin M, Hotamisligil GS. Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance. Proc Natl Acad Sci USA 2006;103:10741–10746.

    Article  PubMed  CAS  Google Scholar 

  23. Meng MJ, Yang QH, Wang Q, Chen XM, Wang FZ, Wang YP, et al. Effects of different therapeutic methods and typical recipes on activation of ERK1/2 in Kupffer cells of rats with fatty liver. Chin J Pathophysiology (Chin) 2007;23:1551–1555.

    Google Scholar 

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Authors and Affiliations

  1. Department of Traditional Chinese Medicine, Medical College, Jinan University, Guangzhou, 510632, China

    Qin-he Yang  (杨钦河), Yu-pei Zhang  (张玉佩), Huan-huan Ping  (平换换), Huan-wen Yang  (杨环文), Tong-yan Chen  (陈同炎) & Hai-tao Liu  (刘海涛)

  2. Qingyuan Maternity and Child Health Care Hospital, Qingyuan City, Guangdong Province, 511515, China

    Si-ping Hu  (胡四平)

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  1. Qin-he Yang  (杨钦河)
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  2. Si-ping Hu  (胡四平)
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  3. Yu-pei Zhang  (张玉佩)
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  4. Huan-huan Ping  (平换换)
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  5. Huan-wen Yang  (杨环文)
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  6. Tong-yan Chen  (陈同炎)
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  7. Hai-tao Liu  (刘海涛)
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Correspondence to Qin-he Yang  (杨钦河).

Additional information

Supported by the National Natural Science Foundation of China (No. 30371726)

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Yang, Qh., Hu, Sp., Zhang, Yp. et al. Effects of different therapeutic methods and typical recipes of Chinese medicine on activation of c-Jun N-terminal Kinase in Kupffer cells of rats with fatty liver disease. Chin. J. Integr. Med. 18, 769–774 (2012). https://doi.org/10.1007/s11655-011-0691-5

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  • DOI: https://doi.org/10.1007/s11655-011-0691-5

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