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Rhein lysinate decreases inflammation and adipose infiltration in KK/HlJ diabetic mice with non-alcoholic fatty liver disease

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Abstract

The objective of this study was to investigate the protective effects of rhein lysinate (RHL) on the liver. Mice were divided into four groups: C57BL/J control, the KK/HlJ diabetic model, and 25 and 50 mg/kg/day RHL-treated KK/HlJ groups. The KK/HlJ diabetic mouse model was made by injecting STZ and feeding mice diabetic food. At 16 weeks, mice were sacrificed and their livers were harvested. The results indicated that compared with the C57BL/J control group, the body weights, liver weights and liver weight-to-body weight ratio were increased in KK/HlJ diabetic mice; however, these values were decreased following treatment with RHL. Compared with the C57BL/J control, KK/HlJ diabetic mice had a significantly lower level of SOD and GSH-px in their livers, but had a significantly higher level of MDA. However, these effects were ameliorated by RHL. Hepatic adipose infiltration was observed in KK/HlJ mice, but not in C57BL/J mice. RHL decreased the incidence of hepatic adipose infiltration and significantly decreased the expression of TNF-α, IL-6, NF-κB, SREBP-1c, and Fas, as well as the phosphorylation of NF-κB in the liver. In conclusion, RHL can improve hepatic function by decreasing hepatic adipose infiltration and the expression of inflammatory factors.

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References

  • Ahmed AR, Wong J, Harrison SA (2015) Nonalcoholic fatty liver disease review: diagnosis, treatment, and outcomes. Clin Gastroenterol Hepatol 13:2062–2070

    Article  PubMed  Google Scholar 

  • Akram Kooshki A, Tofighiyan T, Rakhshani MH (2015) Effects of synbiotics on inflammatory markers in patients with type 2 diabetes mellitus. Glob J Health Sci 7:1–5

    CAS  PubMed  PubMed Central  Google Scholar 

  • Angulo P (2002) Nonalcoholic fatty liver disease. N Engl J Med 346:1221–1231

    Article  CAS  PubMed  Google Scholar 

  • Bhatt HB, Smith RJ (2015) Fatty liver disease in diabetes mellitus. Hepatobiliary Surg Nutr 4:101–108

    PubMed  PubMed Central  Google Scholar 

  • Calisir IA, Filik L (2015) Nonalcoholic fatty liver disease and hemorrhoids. Eur J Gastroenterol Hepatol 27:1229–1230

    Article  PubMed  Google Scholar 

  • Celebi G, Genc H, Gurel H, Sertoglu E, Kara M, Tapan S, Acikel C, Karslioglu Y, Ercin CN, Dogru T (2015) The relationship of circulating fetuin-a with liver histology and biomarkers of systemic inflammation in nondiabetic subjects with nonalcoholic fatty liver disease. Saudi J Gastroenterol 21:139–145

    Article  PubMed  PubMed Central  Google Scholar 

  • Chen WY, Chen CJ, Liu CH, Mao FC (2010) Chromium attenuates high-fat diet-induced nonalcoholic fatty liver disease in KK/HlJ mice. Biochem Biophys Res Commun 397:459–464

    Article  CAS  PubMed  Google Scholar 

  • Folch J, Lees M, Sloane stanley GH (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226:497–509

    CAS  PubMed  Google Scholar 

  • Fusillo S, Rudolph B (2015) Nonalcoholic fatty liver disease. Pediatr Rev 36:198–205

    Article  PubMed  Google Scholar 

  • He Q, Li JK, Li F, Li RG, Zhan GQ, Li G, Du WX, Tan HB (2015) Mechanism of action of gypenosides on type 2 diabetes and non-alcoholic fatty liver disease in rats. World J Gastroenterol 21:2058–2066

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hu G, Liu J, Zhen YZ, Xu R, Qiao Y, Wei J, Tu P, Lin YJ (2013) Rhein lysinate increases the median survival time of SAMP10 mice: protective role in the kidney. Acta Pharmacol Sin 34:515–521

    Article  PubMed  PubMed Central  Google Scholar 

  • Hur W, Lee JH, Kim SW, Kim JH, Bae SH, Kim M, Hwang D, Kim YS, Park T, Um SJ, Song BJ, Yoon SK (2015) Downregulation of microRNA-451 in non-alcoholic steatohepatitis inhibits fatty acid-induced proinflammatory cytokine production through the AMPK/AKT pathway. Int J Biochem Cell Biol 64:265–276

    Article  CAS  PubMed  Google Scholar 

  • Ikejima K, Okumura K, Kon K, Takei Y, Sato N (2007) Role of adipocytokines in hepatic fibrogenesis. J Gastroenterol Hepatol 22:S87–S92

    Article  CAS  PubMed  Google Scholar 

  • Lee HJ, Hong YS, Jun W, Yang SJ (2015) Nicotinamide riboside ameliorates hepatic metaflammation by modulating nlrp3 inflammasome in a rodent model of type 2 diabetes. J Med Food 18:1207–1213

    Article  CAS  PubMed  Google Scholar 

  • Lin YJ, Zhen YS (2009) Rhein lysinate suppresses the growth of breast cancer cells and potentiates the inhibitory effect of Taxol in athymic mice. Anticancer Drugs 20:65–72

    Article  CAS  PubMed  Google Scholar 

  • Lin YJ, Hu G, Li KJ, Zhao YF, Wei J, Zhen YZ (2015) The protection of Rhein lysinate to liver in diabetic mice induced by high-fat diet and streptozotocin. Arch Pharm Res 38:885–892

    Article  CAS  PubMed  Google Scholar 

  • Lonardo A, Ballestri S, Marchesini G, Angulo P, Loria P (2015) Nonalcoholic fatty liver disease: a precursor of the metabolic syndrome. Dig Liver Dis 47:181–190

    Article  PubMed  Google Scholar 

  • Lv Q, Zhen Q, Liu L, Gao R, Yang S, Zhou H, Goswami R, Li Q (2015) AMP-kinase pathway is involved in tumor necrosis factor alpha-induced lipid accumulation in human hepatoma cells. Life Sci 131:23–29

    Article  CAS  PubMed  Google Scholar 

  • Meng H, Zhang D, Yang H (2013) Effects of amyloid precursor protein 17 peptide on the protection of diabetic encephalopathy and improvement of glycol metabolism in the diabetic rat. J Diabetes Res 2013:689841

    PubMed  PubMed Central  Google Scholar 

  • Nolasco EL, Zanoni FL, Nunes FP, Ferreira SS, Freitas LA, Silva MC, Martins JO (2015) Insulin modulates liver function in a type i diabetes rat model. Cell Physiol Biochem 36:1467–1479

    Article  CAS  PubMed  Google Scholar 

  • Prakash P, Singh V, Jain M, Rana M, Khanna V, Barthwal MK, Dikshit M (2014) Silymarin ameliorates fructose induced insulin resistance syndrome by reducing de novo hepatic lipogenesis in the rat. Eur J Pharmacol 727:15–28

    Article  CAS  PubMed  Google Scholar 

  • Qi Z, Fujita H, Jin J, Davis LS, Wang Y, Fogo AB, Breyer MD (2005) Characterization of susceptibility of inbred mouse strains to diabetic nephropathy. Diabetes 54:2628–2637

    Article  CAS  PubMed  Google Scholar 

  • Rinella ME (2015) Nonalcoholic fatty liver disease: a systematic review. JAMA 313:2263–2273

    Article  CAS  PubMed  Google Scholar 

  • Sheng X, Wang M, Lu M, Xi B, Sheng H, Zang YQ (2011) Rhein ameliorates fatty liver disease through negative energy balance, hepatic lipogenic regulation, and immunomodulation in diet-induced obese mice. Am J Physiol Endocrinol Metab 300:E886–E893

    Article  CAS  PubMed  Google Scholar 

  • Stefan N, Haring HU (2011) The metabolically benign and malignant fatty liver. Diabetes 60:2011–2017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Stojsavljevic S, Gomercic Palcic M, Virovic Jukic L, Smircic Duvnjak L, Duvnjak M (2014) Adipokines and proinflammatory cytokines, the key mediators in the pathogenesis of nonalcoholic fatty liver disease. World J Gastroenterol 20:18070–18091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang W, Zeng L, Yin J, Yao Y, Feng L, Yao X, Sun X, Zhou B (2015) Hugan Qingzhi exerts anti-inflammatory effects in a rat model of nonalcoholic fatty liver disease. Evid Based Complement Alternat Med 2015:810369

    PubMed  PubMed Central  Google Scholar 

  • Wang SS, Purdue MP, Cerhan JR, Zheng T, Menashe I, Armstrong BK, Lan Q, Hartge P, Kricker A, Zhang Y, Morton LM, Vajdic CM, Holford TR, Severson RK, Grulich A, Leaderer BP, Davis S, Cozen W, Yeager M, Chanock SJ, Chatterjee N, Rothman N (2009) Common gene variants in the tumor necrosis factor (TNF) and TNF receptor superfamilies and NF-kB transcription factors and non-Hodgkin lymphoma risk. PLoS One 4(4):e5360

    Article  PubMed  PubMed Central  Google Scholar 

  • Yang XW, Liu FQ, Guo JJ, Yao WJ, Li QQ, Liu TH, Xu LP (2015) Antioxidation and anti-inflammatory activity of Tang Bi Kang in rats with diabetic peripheral neuropathy. BMC Compl Altern Med 15:66

    Article  Google Scholar 

  • Zhao YL, Zhou GD, Yang HB, Wang JB, Shan LM, Li RS, Xiao XH (2011) Rhein protects against acetaminophen-induced hepatic and renal toxicity. Food Chem Toxicol 49:1705–1710

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a grant from the National Natural Science Foundation of China (31400995) and (81470427).

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Correspondence to Ya-Jun Lin.

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Wei, J., Zhen, YZ., Cui, J. et al. Rhein lysinate decreases inflammation and adipose infiltration in KK/HlJ diabetic mice with non-alcoholic fatty liver disease. Arch. Pharm. Res. 39, 960–969 (2016). https://doi.org/10.1007/s12272-016-0770-4

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  • DOI: https://doi.org/10.1007/s12272-016-0770-4

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