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Protective Effects of Chaihu Shugan San (柴胡疏肝散) on Nonalcoholic Fatty Liver Disease in Rats with Insulin Resistance

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Abstract

Objective

To investigate the protective effects of Chinese medicine formulation Chaihu Shugan San (柴胡疏肝散, CHSGS) on nonalcoholic fatty liver disease (NAFLD) in rats with insulin resistance (IR) and its molecular mechanisms.

Methods

Male Sprague-Dawley rats were randomly divided into six groups: the control group, the model group, Dongbao Gantai group (东宝肝泰, DBGT, 0.09 g methionine/kg), CHSGS high-dose group (CHSG-H, 12.6 g crude drug/kg), CHSGS medium-dose group (CHSG-M, 6.3 g crude drug/kg), and CHSGS low-dose group (CHSG-L, 3.15 g crude drug/kg). After establishing the NAFLD rat model and treatment for 8 weeks, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), free fatty acid (FFA), fasting blood glucose (FBG), fasting insulin (FINS) contents in blood serum, and TC, TG contents in the hepatic homogenate were measured by an automatic biochemical analyzer, and a homeostasis model assessment was applied to assess the status of IR, insulin sensitivity index (ISI), and homeostasis model assessment for insulin secretion (HOMA-IS). The expression levels of adiponectin and leptin mRNA in liver tissue were analyzed by reverse transcription polymerase chain reaction. Pathological changes of livers were observed by hematoxylin-eosin staining of paraffin section.

Results

Compared with the model group, the serum levels of TC, TG, FFA, FBG, FINS, IRI, ISI, and the liver levels of TC and TG in CHSG-H, CHSG-M, CHSG-L groups showed significant declines (P<0.01 or P<0.05); the serum levels of HDL-C, HOMA-IS were significantly increased (P<0.01 or P<0.05); the expression of leptin mRNA was dramatically decreased and the expression of adiponectin mRNA was increased in the hepatic tissue (P<0.01 or P<0.05). The fatty deposition of liver cells could also be alleviated.

Conclusion

CHSGS could up-regulate the expression of adiponectin mRNA and down-regulate the expression of leptin mRNA on the liver, suggesting the CHSGS had positive therapeutic effect on NAFLD in rats with IR.

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References

  1. Ortiz-Lopez C, Lomonaco R, Orsak B, Finch J, Chang Z, Kochunov VG, et al. Prevalence of prediabetes and diabetes and metabolic profile of patients with nonalcoholic fatty liver disease (NAFLD). Diabetes Care 2012;35:873–874.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Farrell GC, Larter CZ. Nonalcoholic fatty liver disease: from steatosis to cirrhosis. Hepatology 2006;43 (2 Suppl 1):S99–S112.

    Article  CAS  PubMed  Google Scholar 

  3. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001;7:941–946.

    Article  CAS  PubMed  Google Scholar 

  4. Yadav A, Kataria MA, Saini V, Yadav A. Role of leptin and adiponectin in insulin resistance. Clin Chim Acta 2013;417:80–84.

    Article  CAS  PubMed  Google Scholar 

  5. Li F, Yang WY, Liang R, Liu XL, Qu D. Understanding the role of the liver in adjusting stress reactions. J Beijing Univ Tradit Chin Med (Chin) 1998;21:20–23.

    CAS  Google Scholar 

  6. Li SQ, Su ZH, Peng JB, Zou ZM, Yu CY. In vitro and in vivo antioxidant effects and the possible relationship between the antidepression efficacy of traditional Chinese medicine formulation Chaihu Shugan San. Chin J Natural Med 2010;8:353–361.

    Article  Google Scholar 

  7. Li D, Jiang T, Fan HQ, Liang WN, Xiong KZ, Tang CP. Influence of Chaihushugan San on lipid metabolism and liver function in nonalcoholic fatty liver rats. Pharmacol Clin Chin Materia Med (Chin) 2013;29:8–11.

    Google Scholar 

  8. Mili S, Luli D, Stimac D. Non-alcoholic fatty liver disease and obesity: Biochemical, metabolic and clinical presentations. World J Gastroenterol 2014;20:9330–9337.

    Google Scholar 

  9. Kucera O, Cervinkova Z. Experimental models of nonalcoholic fatty liver disease in rats. World J Gastroenterol 2014;20:8364–8376.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Zhang ZP, You TT, Zou LY, Wu T, Wu Y, Cui L. Effect of a compound Danshen preparation in preventing long-term gastric lipid emulsion administration-induced nonalcoholic steatohepatitis in rats. J Southern Med Univ (Chin) 2008;28:1109–1113.

    CAS  Google Scholar 

  11. Yao HX, Guo J, Tang CP, Yang CY, Chen YF, Chen YF, et al. Liver hypolipidemic protection of Compound Zhenzhu Tiaozhi Capsula on nonalcoholic fatty liver disease in rats and its mechanism. Chin Tradit Herbal Drugs (Chin) 2011;42:2075–2076.

    Google Scholar 

  12. Zhang L. The observation of Chaihu Shugan San clinical effect on non-alcoholic fatty liver. Chin Med Modern Distance Educ (Chin) 2013;11:90–91.

    Google Scholar 

  13. Zhang YH, Zhou M, Chen SW. Pharmacological study on Dongbaogantai pill. Chin Community Doctors (Chin) 2010;27:17.

    Google Scholar 

  14. Su DM, Li J, Zhuge L, Li JX. Influences of Jianpi Shugan Fang on ADP and TNF-α in rats with non-alcoholic steatohepatitis. J Beijing Univ Tradit Chin Med (Chin) 2011;34:826–831.

    Google Scholar 

  15. Fan JG. Nonalcoholic fatty liver disease diagnosis and treatment guidelines (recension in 2010). Chin J Gastroenterol Hepatol (Chin) 2010;19:483–484.

    Google Scholar 

  16. Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care 2004;27:1487–1495.

    Article  PubMed  Google Scholar 

  17. Varela-Rey M, Embade N, Ariz U, Lu SC, Mato JM, Martínez-Chantar ML. Non-alcoholic steatohepatitis and animal models: understanding the human disease. Int J Biochem Cell Biol 2009;41:969–976.

    Article  CAS  PubMed  Google Scholar 

  18. Malaguarnera M, Di Rosa M, Nicoletti F, Malaguarnera L. Molecular mechanisms involved in NAFLD progression. J Mol Med 2009;87:679–695.

    Article  CAS  PubMed  Google Scholar 

  19. Charlton M, Sreekumar R, Rasmussen D, Lindor K, Nair KS. Apolipoprotein synthesis in nonalcoholic steatohepatitis. Hepatology 2002;35:898–904.

    Article  CAS  PubMed  Google Scholar 

  20. Lu LG, Zeng MD. The role of improving insulin resistant in the treatment and prevention of nonalcoholic fatty liver disease. Chin J Hepatol (Chin) 2003;11:113–114.

    Google Scholar 

  21. Seki S, Kitada T, Yamada T, Sakaguchi H, Nakatani K, Wakasa K. In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver disease. J Hepatol 2002;37:56–62.

    Article  CAS  PubMed  Google Scholar 

  22. Almonacid-Urrego CC, Sánchez-Campos S, Tuñón MJ, González-Gallego J. Non-alcoholic steatohepatitis: What can we learn from animal models? Current Med Chem 2012;19:1389–1404.

    Article  CAS  Google Scholar 

  23. You M, Considine RV, Leone TC, Kelly DP, Crabb DW. Role of adiponectin in the protective action of dietary saturated fat against alcoholic fatty liver in mice. Hepatology 2005;42:568–577.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Naderali EK, Brwon MJ, Pickavance LC, Wilding JP, Doyle PJ, Williams G. Dietary obesity in the rat induces endothelial dysfunction without causing insulin resistance: a possible role for triacylglycerols. Clin Sci 2001;101:499–506.

    Article  CAS  PubMed  Google Scholar 

  25. Procaccini C, Galgani M, De Rosa V, Carbone F, Rocca C, Ranucci G, et al. Leptin: the prototypic adipocytokine and its role in NAFLD. Curr Pharm Des 2010;16:1902–1912.

    Article  CAS  PubMed  Google Scholar 

  26. Huang XD, Fan Y, Zhang H, Carbone F, La Rocca C, Ranucci G, et al. Serum leptin and soluble leptin receptor in non-alcoholic fatty liver disease. World J Gastroenterol 2008;14:2888–2893.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Sehattenberg JM, Wang Y, Czaja MJ, Rigoli RM, Czaja MJ. Hepatoeyte CYP2E1 overexpression and steatohepatitis lead to impaired hepatic insulin signaling. J Biol Chem 2005;280:9887–9894.

    Article  Google Scholar 

  28. Zhu WF, Zhao Y, Xu KM, Shi MJ, Chen LH. Action mechanism of Dongbaogantai tablet in the prevention and treatment of alcoholic fatty liver in rats. China Pharm (Chin) 2009;20:2179–2181.

    Google Scholar 

  29. Zhao CP, Sun XN, Yu JZ. A clinical study on treating fatty liver with Jiangzhi Yigan Powder and Dongbao Gantai Pill. J Chin Med (Chin) 2005;20:34–35.

    Google Scholar 

  30. Li J, Li P. 149 cases of clinical observation on treatment of fatty liver with Dongbaogantai and Zhibituo. Sichuan Med J (Chin) 2000;21:724.

    Google Scholar 

  31. Yan M. Medicine research of non-alcoholic fatty liver. Clin J Chin Med (Chin) 2012;3:118–120.

    Google Scholar 

  32. Ge HY, Chen B, Liu HL, Li HQ. Therapeutic effects of saikoside on alcoholic liver disease in rats. Chin J Gerontol (Chin) 2011;31:662–663.

    CAS  Google Scholar 

  33. Chen JM, Zhang SS, Guo QK, Peng B, Peng YY, Li FY, et al. Study on the curative effect and the protection mechanism of Paeoniflorin on nonalcoholic fatty liver rats. China J Tradit Chin Med Pharm 2013;28:1376–1381.

    CAS  Google Scholar 

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Authors and Affiliations

  1. School of Chinese Material Medica, Guangdong Pharmaceutical University, Guangzhou, 510006, China

    Wei-ning Jiang, Dan Li, Yan-fen Chen, Jie Wang, Yun Zhou, Chao-yan Yang & Chun-ping Tang

  2. Center of Laboratorial Animals, Guangdong Pharmaceutical University, Guangzhou, 510006, China

    Tao Jiang

  3. Guangdong Traditional Chinese Medicine Key Laboratory for Metabolic Diseases, Guangzhou, 510006, China

    Jiao Guo

Authors
  1. Wei-ning Jiang
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  2. Dan Li
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  3. Tao Jiang
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  4. Jiao Guo
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  5. Yan-fen Chen
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  6. Jie Wang
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  7. Yun Zhou
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  8. Chao-yan Yang
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  9. Chun-ping Tang
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Corresponding author

Correspondence to Chun-ping Tang.

Additional information

Suppport by the National Natural Science Foundation of China (No. 30973913) and the Science Foundation of Science and Technology Bureau of Guangdong (No. 2008A030101005)

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Jiang, Wn., Li, D., Jiang, T. et al. Protective Effects of Chaihu Shugan San (柴胡疏肝散) on Nonalcoholic Fatty Liver Disease in Rats with Insulin Resistance. Chin. J. Integr. Med. 24, 125–132 (2018). https://doi.org/10.1007/s11655-016-2252-4

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  • DOI: https://doi.org/10.1007/s11655-016-2252-4

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