Extract of Rhus verniciflua stokes protects the diet-induced hyperlipidemia in mice

Abstract

Rhus verniciflua stokes (RVS) is a popular medicinal plant in oriental medicines which is commonly used to resolve extravasated blood. To elucidate the molecular mechanism of the role of RVS extracts on the regulation of lipid and cholesterol biosynthesis, we investigated whether RVS extract protect the hyperlipidemia in western diet-induced C57BL6/J mice. Mice fed a western diet and additionally RVS extracts was administered orally at a dose of 0.1 or 1 g/kg/day for 2 weeks respectively. Group with higher dose of RVS extract showed a significantly decreased body weight compared with western diet fed mice groups. And total cholesterol, LDL-cholesterol levels and fatty liver formation were also improved especially in group of mice fed western diet supplemented high dose RVS extracts. Next, synthesis of hepatic bile acids were significantly increased in RVS extract fed groups. Furthermore, RVS extracts significantly increase promoter activity of Cyp7a1 via up-regulate the transcriptional expression level of LXRα. Our data suggest that RVS extracts could be a potent therapeutic ingredient for prevent a hyperlipidemia via increase of bile acids biosynthesis.

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References

  1. Carr, M.C., and J.D. Brunzell. 2004. Abdominal obesity and dyslipidemia in the metabolic syndrome: importance of type 2 diabetes and familial combined hyperlipidemia in coronary artery disease risk. Journal of Clinical Endocrinology and Metabolism 89: 2601–2607.

    CAS  Article  PubMed  Google Scholar 

  2. Chiang, J.Y. 2009. Bile acids: Regulation of synthesis. Journal of Lipid Research 50: 1955–1966.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  3. Han, Q.B., J.Z. Song, C.F. Qiao, L. Wong, and H.X. Xu. 2006. Preparative separation of gambogic acid and its C-2 epimer using recycling high-speed counter-current chromatography. Journal of Chromatography A 1127: 298–301.

    CAS  Article  PubMed  Google Scholar 

  4. Hong, D.H., S.B. Han, C.W. Lee, S.H. Park, Y.J. Jeon, M.J. Kim, S.S. Kwak, and H.M. Kim. 1999. Cytotoxicity of urushiols isolated from sap of Korean lacquer tree (Rhus vernicifera Stokes). Archives of Pharmacal Research 22: 638–641.

    CAS  Article  PubMed  Google Scholar 

  5. Jang, H.S., S.H. Kook, Y.O. Son, J.G. Kim, Y.M. Jeon, Y.S. Jang, K.C. Choi, J. Kim, S.K. Han, K.Y. Lee, B.K. Park, N.P. Cho, and J.C. Lee. 2005. Flavonoids purified from Rhus verniciflua stokes actively inhibit cell growth and induce apoptosis in human osteosarcoma cells. Biochimica et Biophysica Acta 1726: 309–316.

    CAS  Article  PubMed  Google Scholar 

  6. Janowski, B.A., P.J. Willy, T.R. Devi, J.R. Falck, and D.J. Mangelsdorf. 1996. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature 383: 728–731.

    CAS  Article  PubMed  Google Scholar 

  7. Jeon, W.K., J.H. Lee, H.K. Kim, A.Y. Lee, S.O. Lee, Y.S. Kim, S.Y. Ryu, S.Y. Kim, Y.J. Lee, and B.S. Ko. 2006. Anti-platelet effects of bioactive compounds isolated from the bark of Rhus verniciflua stokes. Journal of Ethnopharmacology 106: 62–69.

    CAS  Article  PubMed  Google Scholar 

  8. Jung, C.H., C.Y. Jun, S. Lee, C.H. Park, K. Cho, and S.G. Ko. 2006. Rhus verniciflua stokes extract: radical scavenging activities and protective effects on H2O2-induced cytotoxicity in macrophage RAW 264.7 cell lines. Biological and Pharmaceutical Bulletin 29: 1603–1607.

    CAS  Article  PubMed  Google Scholar 

  9. Jung, C.H., J.H. Kim, M.H. Hong, H.M. Seog, S.H. Oh, P.J. Lee, G.J. Kim, H.M. Kim, J.Y. Um, and S.G. Ko. 2007. Phenolic-rich fraction from Rhus verniciflua stokes (RVS) suppress inflammatory response via NF-kappaB and JNK pathway in lipopolysaccharide-induced RAW 264.7 macrophages. Journal of Ethnopharmacology 110: 490–497.

    Article  PubMed  Google Scholar 

  10. Kim, J.H., H.Y. Go, D.H. Jin, H.P. Kim, M.H. Hong, W.Y. Chung, J.H. Park, J.B. Jang, H. Jung, Y.C. Shin, S.H. Kim, and S.G. Ko. 2008. Inhibition of the PI3 K-Akt/PKB survival pathway enhanced an ethanol extract of Rhus verniciflua stokes-induced apoptosis via a mitochondrial pathway in AGS gastric cancer cell lines. Cancer Letters 265: 197–205.

    CAS  Article  PubMed  Google Scholar 

  11. Kim, S.A., S.H. Kim, I.S. Kim, D. Lee, M.S. Dong, C.S. Na, N.X. Nhiem, and H.H. Yoo. 2013. Simultaneous determination of bioactive phenolic compounds in the stem extract of Rhus verniciflua stokes by high performance liquid chromatography. Food Chemistry 141: 3813–3819.

    CAS  Article  PubMed  Google Scholar 

  12. Kleiner, D.E., E.M. Brunt, M. Van Natta, C. Behling, M.J. Contos, O.W. Cummings, L.D. Ferrell, Y.C. Liu, M.S. Torbenson, A. Unalp-Arida, M. Yeh, A.J. Mccullough, and A.J. Sanyal. 2005. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41: 1313–1321.

    Article  PubMed  Google Scholar 

  13. Lee, J.C., K.T. Lim, and Y.S. Jang. 2002. Identification of Rhus verniciflua stokes compounds that exhibit free radical scavenging and anti-apoptotic properties. Biochimica et Biophysica Acta 1570: 181–191.

    CAS  Article  PubMed  Google Scholar 

  14. Lee, J.D., J.E. Huh, G. Jeon, H.R. Yang, H.S. Woo, D.Y. Choi, and D.S. Park. 2009. Flavonol-rich RVHxR from Rhus verniciflua stokes and its major compound fisetin inhibits inflammation-related cytokines and angiogenic factor in rheumatoid arthritic fibroblast-like synovial cells and in vivo models. International Immunopharmacology 9: 268–276.

    CAS  Article  PubMed  Google Scholar 

  15. Lehmann, J.M., S.A. Kliewer, L.B. Moore, T.A. Smith-Oliver, B.B. Oliver, J.L. Su, S.S. Sundseth, D.A. Winegar, D.E. Blanchard, T.A. Spencer, and T.M. Willson. 1997. Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. Journal of Biological Chemistry 272: 3137–3140.

    CAS  Article  PubMed  Google Scholar 

  16. Lim, K.T., C. Hu, and D.D. Kitts. 2001. Antioxidant activity of a Rhus verniciflua stokes ethanol extract. Food and Chemical Toxicology 39: 229–237.

    CAS  Article  PubMed  Google Scholar 

  17. Lusis, A.J. 2000. Atherosclerosis. Nature 407: 233–241.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  18. Oh, P.S., S.J. Lee, and K.T. Lim. 2006. Hypolipidemic and antioxidative effects of the plant glycoprotein (36 kDa) from Rhus verniciflua stokes fruit in Triton WR-1339-induced hyperlipidemic mice. Bioscience, Biotechnology, and Biochemistry 70: 447–456.

    CAS  Article  PubMed  Google Scholar 

  19. Park, J.G., and G.T. Oh. 2011. The role of peroxidases in the pathogenesis of atherosclerosis. BMB Reports 44: 497–505.

    CAS  Article  PubMed  Google Scholar 

  20. Peet, D.J., S.D. Turley, W. Ma, B.A. Janowski, J.M. Lobaccaro, R.E. Hammer, and D.J. Mangelsdorf. 1998. Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha. Cell 93: 693–704.

    CAS  Article  PubMed  Google Scholar 

  21. Plump, A.S., J.D. Smith, T. Hayek, K. Aalto-Setala, A. Walsh, J.G. Verstuyft, E.M. Rubin, and J.L. Breslow. 1992. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell 71: 343–353.

    CAS  Article  PubMed  Google Scholar 

  22. Russell, D.W. 2003. The enzymes, regulation, and genetics of bile acid synthesis. Annual Review of Biochemistry 72: 137–174.

    CAS  Article  PubMed  Google Scholar 

  23. Song, N.J., H.J. Yoon, K.H. Kim, S.R. Jung, W.S. Jang, C.R. Seo, Y.M. Lee, D.H. Kweon, J.W. Hong, J.S. Lee, K.M. Park, K.R. Lee, and K.W. Park. 2013. Butein is a novel anti-adipogenic compound. Journal of Lipid Research 54: 1385–1396.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  24. Suk, K.T., S.K. Baik, H.S. Kim, S.M. Park, K.J. Paeng, Y. Uh, I.H. Jang, M.Y. Cho, E.H. Choi, M.J. Kim, and Y.L. Ham. 2011. Antibacterial effects of the urushiol component in the sap of the lacquer tree (Rhus verniciflua stokes) on Helicobacter pylori. Helicobacter 16: 434–443.

    CAS  Article  PubMed  Google Scholar 

  25. Trauner, M., and E. Halilbasic. 2011. Nuclear receptors as new perspective for the management of liver diseases. Gastroenterology 140(1120–1125): e1–e12.

    PubMed  Google Scholar 

  26. Turek, F.W., C. Joshu, A. Kohsaka, E. Lin, G. Ivanova, E. Mcdearmon, A. Laposky, S. Losee-Olson, A. Easton, D.R. Jensen, R.H. Eckel, J.S. Takahashi, and J. Bass. 2005. Obesity and metabolic syndrome in circadian Clock mutant mice. Science 308: 1043–1045.

    PubMed Central  CAS  Article  PubMed  Google Scholar 

  27. Wiegman, A., B.A. Hutten, E. De Groot, J. Rodenburg, H.D. Bakker, H.R. Buller, E.J. Sijbrands, and J.J. Kastelein. 2004. Efficacy and safety of statin therapy in children with familial hypercholesterolemia: A randomized controlled trial. JAMA 292: 331–337.

    CAS  Article  PubMed  Google Scholar 

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Acknowledgments

This research was supported by Industrialization Support Program for Bio-technology of Agriculture and Forestry, Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea. And this research was also supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MEST) (No. 2012R1A3A2026454).

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The Authors have declared that there is no conflict of interest to disclose.

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Correspondence to Goo Taeg Oh.

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Se-Jin Jeong and Jong-Gil Park have contributed equally to this work.

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Jeong, SJ., Park, JG., Kim, S. et al. Extract of Rhus verniciflua stokes protects the diet-induced hyperlipidemia in mice. Arch. Pharm. Res. 38, 2049–2058 (2015). https://doi.org/10.1007/s12272-015-0579-6

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Keywords

  • Rhus verniciflua stokes (RVS)
  • Hyperlipidemia
  • Bile acid biosynthesis
  • Liver X receptor α (LXRα)
  • Cyp7a1