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DOI QR Code

Oral administration of Jinan Red Ginseng and licorice extract mixtures ameliorates nonalcoholic steatohepatitis by modulating lipogenesis

  • Yang, Daram (Biosafety Research Institute and Laboratory of Pathology, College of Veterinary Medicine, Jeonbuk National University) ;
  • Jeong, Hyuneui (Biosafety Research Institute and Laboratory of Pathology, College of Veterinary Medicine, Jeonbuk National University) ;
  • Hwang, Seung-Mi (Department of Efficacy Study, Institute of Jinan Red Ginseng) ;
  • Kim, Jong-Won (Biosafety Research Institute and Laboratory of Pathology, College of Veterinary Medicine, Jeonbuk National University) ;
  • Moon, Hee-Won (Biosafety Research Institute and Laboratory of Pathology, College of Veterinary Medicine, Jeonbuk National University) ;
  • Lee, Ye-Eun (Department of Efficacy Study, Institute of Jinan Red Ginseng) ;
  • Oh, Hyo-Bin (Department of Efficacy Study, Institute of Jinan Red Ginseng) ;
  • Park, Chung-berm (Department of Efficacy Study, Institute of Jinan Red Ginseng) ;
  • Kim, Bumseok (Biosafety Research Institute and Laboratory of Pathology, College of Veterinary Medicine, Jeonbuk National University)
  • 투고 : 2021.03.17
  • 심사 : 2021.05.12
  • 발행 : 2022.01.01

초록

Background: Nonalcoholic steatohepatitis (NASH) is one of the main chronic liver diseases. NASH is identified by lipid accumulation, inflammation, and fibrosis. Jinan Red Ginseng (JRG) and licorice have been widely used because of their anti-inflammatory and hepatoprotective effects. Hence, this study assessed JRG and licorice extract mixtures' effects on NASH progression. Methods: Palmitic acid (PA) and the western diet (WD) plus, high glucose-fructose water were used to induce in vitro and in vivo NASH. Mice were orally administered with JRG-single (JRG-S) and JRG-mixtures (JRG-M; JRG-S + licorice) at 0, 50, 100, 200 or 400 mg/kg/day once a day during the last half-period of diet feeding. Results: JRG-S and JRG-M reduced NASH-related pathologies in WD-fed mice. JRG-S and JRG-M consistently decreased the mRNA level of genes related with inflammation, fibrosis, and lipid metabolism. The treatment of JRG-S and JRG-M also diminished the SREBP-1c protein levels and the p-AMPK/AMPK ratio. The FAS protein levels were decreased by JRG-M treatment both in vivo and in vitro but not JRG-S. Conclusion: JRG-M effectively reduced lipogenesis by modulating AMPK downstream signaling. Our findings suggest that this mixture can be used as a prophylactic or therapeutic alternative for the remedy of NASH.

키워드

과제정보

This study was supported by the Ministry of Agriculture, Food and Rural Affairs (MAFRA), through the 2015 Healthy Local Food Branding Project of the Rural Resources Complex Industrialization Support Program.

참고문헌

  1. Raffaele M, Licari M, Amin S, Alex R, Shen HH, Singh SP, Vanella L, Rezzani R, Bonomini F, Peterson SJ. Cold press pomegranate seed oil attenuates dietary-obesity induced hepatic steatosis and fibrosis through antioxidant and mitochondrial pathways in obese mice. Int J Mol Sci 2020;21:5469. https://doi.org/10.3390/ijms21155469
  2. Neuschwander-Tetri BA, Caldwell SH. Nonalcoholic steatohepatitis: summary of an AASLD single topic conference. Hepatology 2003;37:1202-19. https://doi.org/10.1053/jhep.2003.50193
  3. Bugianesi E, Leone N, Vanni E, Marchesini G, Brunello F, Carucci P, Musso A, De Paolis P, Capussotti L, Salizzoni M, et al. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology 2002;123:134-40. https://doi.org/10.1053/gast.2002.34168
  4. Wree A, Broderick L, Canbay A, Hoffman HM, Feldstein AE. From NAFLD to NASH to cirrhosis-new insights into disease mechanisms. Nat Rev Gastroenterol Hepatol 2013;10:627-36. https://doi.org/10.1038/nrgastro.2013.149
  5. Chen X, Xue H, Fang W, Chen K, Chen S, Yang W, Shen T, Chen X, Zhang P, Ling W. Adropin protects against liver injury in nonalcoholic steatohepatitis via the Nrf2 mediated antioxidant capacity. Redox Biol 2019;21:101068. https://doi.org/10.1016/j.redox.2018.101068
  6. Li H, Zhou Y, Wang H, Zhang M, Qiu P, Zhang M, Zhang R, Zhao Q, Liu J. Crosstalk between liver macrophages and surrounding cells in nonalcoholic steatohepatitis. Front Immunol 2020;11.
  7. Song K, Kwon H, Han C, Chen W, Zhang J, Ma W, Dash S, Gandhi CR, Wu T. Yes-associated protein in kupffer cells enhances the production of prionflammatory cytokines and promotes the development of nonalcoholic steatohepatitis. Hepatology 2020;72:72-87. https://doi.org/10.1002/hep.30990
  8. Kim JH. Cardiovascular diseases and Panax ginseng: a review on molecular mechanisms and medical applications. J Ginseng Res 2012;36:16-26. https://doi.org/10.5142/jgr.2012.36.1.16
  9. Seo SJ, Cho JY, Jeong YH, Choi YS. Effect of Korean red ginseng extract on liver damage induced by short-term and long-term ethanol treatment in rats. J Ginseng Res 2013;37:194-200. https://doi.org/10.5142/jgr.2013.37.194
  10. Heo SB, Lim SW, Jhun JY, Cho ML, Chung BH, Yang CW. Immunological benefits by ginseng through reciprocal regulation of Th17 and Treg cells during cyclosporine-induced immunosuppression. J Ginseng Res 2016;40:18-27. https://doi.org/10.1016/j.jgr.2015.04.005
  11. Hong M, Lee YH, Kim S, Suk KT, Bang CS, Yoon JH, Baik GH, Kim DJ, Kim MJ. Anti-inflammatory and antifatigue effect of Korean Red Ginseng in patients with nonalcoholic fatty liver disease. J Ginseng Res 2016;40:203-10. https://doi.org/10.1016/j.jgr.2015.07.006
  12. Sung KS, Chun C, Kwon YH, Kim KH, Chang CC. Effects of red ginseng component on the antioxidative enzymes activities and lipid peroxidation in the liver of mice. J Ginseng Res 2000;24:29-34.
  13. Kim SH, Kang JS, Lee SJ, Chung YJ. Antidiabetic effect of Korean red ginseng by puffing process in streptozotocin-induced diabetic rats. J Korean Soc Food Sci Nutr 2008;37:701-7. https://doi.org/10.3746/JKFN.2008.37.6.701
  14. Hwang SM, Park CB. Jinan red ginseng extract inhibits triglyceride synthesis via the regulation of LXR-SCD expression in hepatoma cells. Korean J Food Sci Technol 2019;51:558-64. https://doi.org/10.9721/KJFST.2019.51.6.558
  15. Choi YH, Kim SE, Huh J, Han YH, Lee MJ. Antibacterial and antioxidative activity of roasted coffee and red ginseng mixture extracts. J Korean Soc Food Sci Nutr 2012;41:320-6. https://doi.org/10.3746/JKFN.2012.41.3.320
  16. Choi ME, Jeon BK, Kim DS, Mun YJ, Woo WH. A study on application for beauty food of mixture of Korean red ginseng and Fagopyrum esculentum: anti-oxidative effect and collagenase inhibitory activity. Herb Formula Sci 2009;17:153-62.
  17. Zheng Y, Lee EH, Lee JH, In G, Kim J, Lee MH, Lee OH, Kang IJ. Preclinical research on a mixture of red ginseng and licorice extracts in the treatment and prevention of obesity. Nutrients 2020;12:2744. https://doi.org/10.3390/nu12092744
  18. Lee SK, So SH, Hwang EI, Koo BS, Han GH, Ko SB, Kim NM. Effect of ginseng and herbal plant mixtures on anti-obesity in obese SD rat induced by high fat diet. J Korean Soc Food Sci Nutr 2008;37:437-44. https://doi.org/10.3746/JKFN.2008.37.4.437
  19. Ram A, Mabalirajan U, Das M, Bhattacharya I, Dinda AK, Gangal SV, Ghosh B. Glycyrrhizin alleviates experimental allergic asthma in mice. Int Immunopharmacol 2006;6:1468-77. https://doi.org/10.1016/j.intimp.2006.04.020
  20. Zhou Z, Kim JW, Zhao J, Qi J, Choi SJ, Lim CW, Lee MY, Lee K, Kim B. Treatment of cigarette smoke extract and condensate differentially potentiates palmitic acid-induced lipotoxicity and steatohepatitis in vitro. Toxicol In Vitro 2018;52:33-40. https://doi.org/10.1016/j.tiv.2018.05.017
  21. Asgharpour A, Cazanave SC, Pacana T, Seneshaw M, Vincent R, Banini BA, Kumar DP, Daita K, Min HK, Mirshahi F. A diet-induced animal model of nonalcoholic fatty liver disease and hepatocellular cancer. J Hepatol 2016;65:579-88. https://doi.org/10.1016/j.jhep.2016.05.005
  22. Kleiner DE, Brunt EM, Van Natta M, Behling C, Contos MJ, Cummings OW, Ferrell LD, Liu YC, Torbenson MS, Unalp-Arida A. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 2005;41:1313-21. https://doi.org/10.1002/hep.20701
  23. Febbraio MA, Reibe S, Shalapour S, Ooi GJ, Watt MJ, Karin M. Preclinical models for studying NASH-driven HCC: how useful are they? Cell Metab 2019;29:18-26. https://doi.org/10.1016/j.cmet.2018.10.012
  24. Towler MC, Hardie DG. AMP-activated protein kinase in metabolic control and insulin signaling. Circ Res 2007;100:328-41. https://doi.org/10.1161/01.RES.0000256090.42690.05
  25. Shimomura I, Shimano H, Horton JD, Goldstein JL, Brown MS. Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells. J Clin Investig 1997;99:838-45. https://doi.org/10.1172/JCI119247
  26. Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Investig 2002;109:1125-31. https://doi.org/10.1172/JCI15593
  27. Bertolio R, Napoletano F, Mano M, Maurer-Stroh S, Fantuz M, Zannini A, Bicciato S, Sorrentino G, Del Sal G. Sterol regulatory element binding protein 1 couples mechanical cues and lipid metabolism. Nat Commun 2019;10:1-11. https://doi.org/10.1038/s41467-018-07882-8
  28. Tran S, Baba I, Poupel L, Dussaud S, Moreau M, Gelineau A, Marcelin G, Magreau-Davy E, Ouhachi M, Lesnik P. Impaired Kupffer cell self-renewal alters the liver response to lipid overload during non-alcoholic steatohepatitis. Immunity 2020;53:627-40. e5. https://doi.org/10.1016/j.immuni.2020.06.003
  29. Kanuri G, Bergheim I. In vitro and in vivo models of non-alcoholic fatty liver disease (NAFLD). Int J Mol Sci 2013;14:11963-80. https://doi.org/10.3390/ijms140611963
  30. Shan SM, Luo JG, Huang F, Kong LY. Chemical characteristics combined with bioactivity for comprehensive evaluation of Panax ginseng CA Meyer in different ages and seasons based on HPLC-DAD and chemometric methods. J Pharm Biomed Anal 2014;89:76-82. https://doi.org/10.1016/j.jpba.2013.10.030
  31. Shi W, Wang Y, Li J, Zhang H, Ding L. Investigation of ginsenosides in different parts and ages of Panax ginseng. Food Chem 2007;102:664-8. https://doi.org/10.1016/j.foodchem.2006.05.053
  32. In G, Ahn NG, Bae BS, Lee MW, Park HW, Jang KH, Cho BG, Han CK, Park CK, Kwak YS. In situ analysis of chemical components induced by steaming between fresh ginseng, steamed ginseng, and red ginseng. J Ginseng Res 2017;41:361-9. https://doi.org/10.1016/j.jgr.2016.07.004
  33. Kim WY, Kim JM, Han SB, Lee SK, Kim ND, Park MK, Kim CK, Park JH. Steaming of ginseng at high temperature enhances biological activity. J Nat Prod 2000;63:1702-4. https://doi.org/10.1021/np990152b
  34. Yoshida T, Abe K, Ikeda T, Matsushita T, Wake K, Sato T, Sato T, Inoue H. Inhibitory effect of glycyrrhizin on lipopolysaccharide and d-galactosamine-induced mouse liver injury. Eur J Pharmacol 2007. 576:136-42. https://doi.org/10.1016/j.ejphar.2007.08.012
  35. Lee CH, Park SW, Kim YS, Kang SS, Kim JA, Lee SH, Lee SM. Protective mechanism of glycyrrhizin on acute liver injury induced by carbon tetrachloride in mice. Biol Pharm Bull 2007;30:1898-904. https://doi.org/10.1248/bpb.30.1898
  36. Jung JC, Lee YH, Kim SH, Kim KJ, Kim KM, Oh S, Jung YS. Hepatoprotective effect of licorice, the root of Glycyrrhiza uralensis Fischer, in alcohol-induced fatty liver disease. BMC Complement Altern Med 2015;16:1-10. https://doi.org/10.1186/s12906-015-0973-0