Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Ginseng seed oil ameliorates hepatic lipid accumulation in vitro and in vivo

  • Kim, Go Woon (Department of Pharmacology, College of Pharmacy, Kyung Hee University) ;
  • Jo, Hee Kyung (Department of Pharmacology, College of Pharmacy, Kyung Hee University) ;
  • Chung, Sung Hyun (Department of Pharmacology, College of Pharmacy, Kyung Hee University)
  • Received : 2016.12.28
  • Accepted : 2017.04.24
  • Published : 2018.10.15
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Abstract

Background: Despite the large number of studies on ginseng, pharmacological activities of ginseng seed oil (GSO) have not been established. GSO is rich in unsaturated fatty acids, mostly oleic and linoleic acids. Unsaturated fatty acids are known to exert a therapeutic effect in nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the protective effect and underlying mechanisms of GSO against NAFLD using in vitro and in vivo models. Methods: In vitro lipid accumulation was induced by free fatty acid mixture in HepG2 cells and by 3 wk of high fat diet (HFD)-feeding in Sprague-Dawley rats prior to hepatocyte isolation. The effects of GSO against diet-induced hepatic steatosis were further examined in C57BL/6J mice fed a HFD for 12 wk. Results: Oil Red O staining and intracellular triglyceride levels showed marked accumulation of lipid droplets in both HepG2 cells and rat hepatocytes, and these were attenuated by GSO treatment. In HFD-fed mice, GSO improved HFD-induced dyslipidemia and hepatic insulin resistance. Increased hepatic lipid contents were observed in HFD-fed mice and it was lowered in GSO (500 mg/kg)-treated mice by 26.4% which was evident in histological analysis. Pathway analysis of hepatic global gene expression indicated that GSO increased the expression of genes associated with ${\beta}$-oxidation (Ppara, Ppargc1a, Sirt1, and Cpt1a) and decreased the expression of lipogenic genes (Srebf1 and Mlxipl), and these were confirmed with reverse transcription and quantitative polymerase-chain reaction. Conclusion: These findings suggest that GSO has a beneficial effect on NAFLD through the suppression of lipogenesis and stimulation of fatty acid degradation pathway.

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References

  1. Seo E, Kim S, Lee SJ, Oh BC, Jun HS. Ginseng berry extract supplementation improves age-related decline of insulin signaling in mice. Nutrients 2015;7:3038-53. https://doi.org/10.3390/nu7043038
  2. Kim WK, Song SY, Oh WK, Kaewsuwan S, Tran TL, Kim WS, Sung JH. Woundhealing effect of ginsenoside Rd from leaves of Panax ginseng via cyclic AMPdependent protein kinase pathway. Eur J Pharmacol 2013;702:285-93. https://doi.org/10.1016/j.ejphar.2013.01.048
  3. Yang BR, Cheung KK, Zhou X, Xie RF, Cheng PP, Wu S, Zhou ZY, Tang JY, Hoi PM, Wang YH, et al. Amelioration of acute myocardial infarction by saponins from flower buds of Panax notoginseng via pro-angiogenesis and anti-apoptosis. J Ethnopharmacol 2016;181:50-8. https://doi.org/10.1016/j.jep.2016.01.022
  4. Wang Y, Qian P, Liu P, Wei L, Cao M, Zhou L, Zhou D, Lin ZX. Effects of Panax notoginseng flower extract on the TGF-beta/Smad signal transduction pathway in heart remodeling of human chymase transgenic mice. Mol Med Rep 2012;5:1443-8.
  5. Lee MH, Kim SS, Cho CW, Choi SY, In G, Kim KT. Quality and characteristics of ginseng seed oil treated using different extraction methods. J Ginseng Res 2013;37:468-74. https://doi.org/10.5142/jgr.2013.37.468
  6. Beveridge TH, Li TS, Drover JC. Phytosterol content in American ginseng seed oil. J Agric Food Chem 2002;50:744-50. https://doi.org/10.1021/jf010701v
  7. Ko SK, Bae HM, Cho OS, Im BO, Chung SH, Lee BY. Analysis of ginsenoside composition of ginseng berry and seed. Food Sci Biotechnol 2008;17:1379-82.
  8. Jones PJ, Senanayake VK, Pu S, Jenkins DJ, Connelly PW, Lamarche B, Couture P, Charest A, Baril-Gravel L, West SG, et al. DHA-enriched high-oleic acid canola oil improves lipid profile and lowers predicted cardiovascular disease risk in the canola oil multicenter randomized controlled trial. Am J Clin Nutr 2014;100:88-97. https://doi.org/10.3945/ajcn.113.081133
  9. Lee TC, Ivester P, Hester AG, Sergeant S, Case LD, Morgan T, Kouba EO, Chilton FH. The impact of polyunsaturated fatty acid-based dietary supplements on disease biomarkers in a metabolic syndrome/diabetes population. Lipids Health Dis 2014;13:196. https://doi.org/10.1186/1476-511X-13-196
  10. Lee YM, Haastert B, Scherbaum W, Hauner H. A phytosterol-enriched spread improves the lipid profile of subjects with type 2 diabetes mellitusda randomized controlled trial under free-living conditions. Eur J Nutr 2003;42:111-7. https://doi.org/10.1007/s00394-003-0401-y
  11. Chalasani N, Younossi Z, Lavine JE, Diehl AM, Brunt EM, Cusi K, Charlton M, Sanyal AJ. The diagnosis and management of non-alcoholic fatty liver disease: practice Guideline by the American Association for the Study of Liver Diseases, American College of Gastroenterology, and the American Gastroenterological Association. Hepatology 2012;55:2005-23. https://doi.org/10.1002/hep.25762
  12. Than NN, Newsome PN. A concise review of non-alcoholic fatty liver disease. Atherosclerosis 2015;239:192-202. https://doi.org/10.1016/j.atherosclerosis.2015.01.001
  13. Carvalho BS, Irizarry RA. A framework for oligonucleotide microarray preprocessing. Bioinformatics 2010;26:2363-7. https://doi.org/10.1093/bioinformatics/btq431
  14. Breitling R, Armengaud P, Amtmann A, Herzyk P. Rank products: a simple, yet powerful, new method to detect differentially regulated genes in replicated microarray experiments. FEBS Lett 2004;573:83-92. https://doi.org/10.1016/j.febslet.2004.07.055
  15. Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, Amin N, Schwikowski B, Ideker T. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res 2003;13:2498-504. https://doi.org/10.1101/gr.1239303
  16. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, et al. Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A 2005;102:15545-50. https://doi.org/10.1073/pnas.0506580102
  17. Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstrale M, Laurilea E, et al. PGC-1alpharesponsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 2003;34:267-73. https://doi.org/10.1038/ng1180
  18. Marchesini G, Brizi M, Morselli-Labate AM, Bianchi G, Bugianesi E, McCullough AJ, Eorlani G, Melchionda N. Association of nonalcoholic fatty liver disease with insulin resistance. Am J Med 1999;107:450-5. https://doi.org/10.1016/S0002-9343(99)00271-5
  19. Xu ZJ, Fan JG, Ding XD, Qiao L, Wang GL. Characterization of high-fat, dietinduced, non-alcoholic steatohepatitis with fibrosis in rats. Dig Dis Sci 2010;55:931-40. https://doi.org/10.1007/s10620-009-0815-3
  20. Ramirex-Tortosa MC, Grandaos S, Quiles JL. Chemical composition, types and characteristics of olive oil. In: Quiles JL, Ramirez-Tortosa C, Yaqoob P, editors. Olive oil and health. Wallingford: CAB International; 2006. p. 45-62.
  21. Massaro M, De Caterina R. Vasculoprotective effects of oleic acid: epidemiological background and direct vascular antiatherogenic properties. Nutr Metab Cardiovasc Dis 2002;12:42-51.
  22. Parthasarathy S, Khoo JC, Miller E, Barnett J, Witztum JL, Steinberg D. Low density lipoprotein rich in oleic acid is protected against oxidative modification: implications for dietary prevention of atherosclerosis. ProcNatl Acad Sci U S A 1990;87:3894-8. https://doi.org/10.1073/pnas.87.10.3894
  23. William CM. Beneficial nutritional properties of olive oil: implications for postprandial lipoproteins and factor VII. Nutr Metab Cardiovasc Dis 2001;111:246-50.
  24. Souza MR, Diniz Mde F, Medeiros-Filho JE, Araujo MS. Metabolic syndrome and risk factors for non-alcoholic fatty liver disease. Arg Gastroenterol 2012;49:89-96. https://doi.org/10.1590/S0004-28032012000100015
  25. Lin Q, Ruuska SE, Shaw NS, Dong D, Noy N. Ligand selectivity of the peroxisome proliferator-activated receptor alpha. Biochemistry 1999;38:185-90. https://doi.org/10.1021/bi9816094
  26. Purushotham A, Schug TT, Xu Q, Surapureddi S, Guo X, Li X. Hepatocytespecific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. Cell Metab 2009;9:327-38. https://doi.org/10.1016/j.cmet.2009.02.006
  27. Lim JH, Gerhart-Hines Z, Dominy JE, Lee Y, Kim S, Tabata M, Xiang YK, Puigserver P. Oleic acid stimulates complete oxidation of fatty acids through protein kinase A-dependent activation of $SIRT1-PGC1{\alpha}$ complex. J Biol Chem 2013;288:7117-26. https://doi.org/10.1074/jbc.M112.415729
  28. Postic C, Girard J. Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J Clin Invest 2008;118:829-38. https://doi.org/10.1172/JCI34275
  29. Marchesini G, Brizi M, Bianchi G, Tomassetti S, Bugianesi E, Lenzi M, McCullough AJ, Natale S, Forlani G, Melchionda N. Nonalcoholic fatty liver disease: a feature of the metabolic syndrome. Diabetes 2001;50:1844-50. https://doi.org/10.2337/diabetes.50.8.1844
  30. Schwarz JM, Linfoot P, Dare D, Aghajanian K. Hepatic de novo lipogenesis in normoinsulinemic and hyperinsulinemic subjects consuming high-fat, lowcarbohydrate and low-fat, high-carbohydrate isoenergetic diets. Am J Clin Nutr 2003;77:43-50. https://doi.org/10.1093/ajcn/77.1.43
  31. Shimomura I, Bashmakov Y, Horton JD. Increased levels of nuclear SREBP-1c associated with fatty livers in two mouse models of diabetes mellitus. J Biol Chem 1999;274:30028-32. https://doi.org/10.1074/jbc.274.42.30028
  32. Dentin R, Benhamed F, Hainault I, Fauveau V, Foufelle F, Dyck JR, Girard J, Postic C. Liver-specific inhibition of ChREBP improves hepatic steatosis and insulin resistnace in ob/ob mice. Diabetes 2006;55:2159-70. https://doi.org/10.2337/db06-0200
  33. Asrih M, Jornayvaz FR. Inflammation as a potential link between nonalcoholic fatty liver disease and insulin resistance. J Endocrinol 2013;218:R23-36.
  34. Farrell GC, van Rooyen D, Gan L, Chitturi S. NASH is an inflammatory disorder: pathogenic, prognostic and therapeutic implications. Gut Liver 2012;6:149-71. https://doi.org/10.5009/gnl.2012.6.2.149

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