Journal of Physiology & Pathology in Korean Medicine (동의생리병리학회지)

The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine (대한동의생리학회·한의병리학회)
권호 표지
DOI QR코드

DOI QR Code

Study of the Suppressive Effect and Its Mechanism of Amomum Cardamomum L. on Free Fatty Acid-induced Liver Steatosis

지방간에 대한 백두구 에틸아세테이트 추출물의 억제 효과 및 기전 연구

  • Lim, Dong Woo (Department of Pathology, College of Korean Medicine, Dongguk University) ;
  • Kim, Hyuck (Department of Diagnostics, College of Korean Medicine, Dongguk University) ;
  • Park, Sung Yun (Department of Diagnostics, College of Korean Medicine, Dongguk University) ;
  • Park, Sun Dong (Department of Prescription, College of Korean Medicine, Dongguk University) ;
  • Park, Won Hwan (Department of Diagnostics, College of Korean Medicine, Dongguk University) ;
  • Kim, Jai Eun (Department of Pathology, College of Korean Medicine, Dongguk University)
  • 임동우 (동국대학교 한의과대학 병리학교실) ;
  • 김혁 (동국대학교 한의과대학 진단학교실) ;
  • 박성윤 (동국대학교 한의과대학 진단학교실) ;
  • 박선동 (동국대학교 한의과대학 방제학교실) ;
  • 박원환 (동국대학교 한의과대학 진단학교실) ;
  • 김재은 (동국대학교 한의과대학 병리학교실)
  • Received : 2017.04.10
  • Accepted : 2017.06.22
  • Published : 2017.06.25
Download PDF
⟨ Previous Next ⟩

Abstract

Through this study, the authors investigated the anti-steatosis effects of the Amomum cardamomum ethyl acetate fraction in free fatty acids (FFAs)-induced human hepatocellular carcinoma HepG2 cells. The ethyl acetate fraction of Amomum cardamomum (ACEA) was extracted with 70% ethanol and then the extract was evaporated using a rotary evaporator prior to sequential fractionation. Human hepatocellular carcinoma were treated with different concentrations of ACEA in the presence and absence of FFAs. To demonstrate the reactive oxygen species (ROS) scavenging activity, DCFDA level was analyzed by using in vitro assay system. Cell viability, lipid accumulation, intracellular triglycerides, malondialdehyde (MDA), liver steatosis related signaling molecules and inflammatory cytokines such as interleukin (IL)-6, 8, tumor necrosis factor-alpha ($TNF-{\alpha}$) were also investigated. As results, ACEA inhibited the FFAs-induced ROS, lipid accumulation, intracellular triglycerides, and MDA in a dose dependent manner. Treatment of human hepatocellular cells with ACEA induced the phosphorylation of 5' adenosine monophosphate-activated protein kinase (AMPK) and carnitine palmitoyltransferase I (CPT1) expression using western blot analysis. ACEA also potently suppressed the FFAs-induced inflammatory cytokines including IL-6, IL-8 and $TNF-{\alpha}$. These results suggest that the ethyl acetate fraction of Amomum cardamoum extract own inhibitory effects of liver steatosis by inhibiting ROS, lipid accumulation, intracellular triglycerides, MDA through AMPK signaling and anti-inflammatory actions.

Keywords

References

  1. Kumar A, Sharma A, Duseja A, Das A, Dhiman RK, Chawla YK, et al. Patients with nonalcoholic fatty liver disease (NAFDL) have higher oxidative stress in comparison to chronic viral hepatitis. J Clin Exp Hepatol. 2012;3:12-8.
  2. Li S, Tan HY, Wang N, Zhang ZJ, Lao L, Wong CW, Feng Y. The role of oxidative stress and antioxidants in liver diseases. Int J Mol Sci. 2015;16:26087-124. https://doi.org/10.3390/ijms161125942
  3. Griffith CM, Schenker S. The role of nutritional therapy in alcoholic liver disease. Alcohol Res Health. 2006;29:296-306.
  4. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC. McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116:1413-9. https://doi.org/10.1016/S0016-5085(99)70506-8
  5. Marchesini G, Brizi M, Morselli-Labate AM, Buqianesi E, McCullough AJ, Forlani G. Association of nonalcoholic fatty liver diseases with insulin resistance. Am J Med. 1999;107:450-5. https://doi.org/10.1016/S0002-9343(99)00271-5
  6. Sato K, Gosho M, Yamamoto T, Kobayashi Y, Ishii N, Ohashi T, et al. Vitamin E has a beneficial effects on nonalcoholic fatty liver disease: a meta-analysis of randomized controlled trials. Nutrition. 2015;31:323-930.
  7. Rouabhia S, Milic N, Abenavoli L. Metformin in the treatment of non-alcoholic fatty liver disease: safety, efficacy and mechanism. Expert Rev Gastroenterol Hepatol. 2014;8:343-9. https://doi.org/10.1586/17474124.2014.894880
  8. Pastori D, Polimeni L, Baratta F, Pani A, Del Ben M, Anqelico F. The efficacy and safety of statins for the treatment of non-alcoholic fatty liver disease. Dig Liver Dis. 2015;47:4-11. https://doi.org/10.1016/j.dld.2014.07.170
  9. Di Minno MN, Russolilo A, Lupoli R, Ambrosino P, Di Minno A, Tarantino G. Omega-3 fatty acids for the treatment of non-alcoholic fatty liver disease. World J Gastroenterol. 2012;18:5839-47. https://doi.org/10.3748/wjg.v18.i41.5839
  10. Heo J. Translated Dongeuibogam. 1st ed. Seoul: Bubinmunwha; 1999.
  11. Lee DH, Kang SS, Chang IM, Mar W. Detection of anti-inflammatory agents from natural products as inhibitors of cyclooxygenase I and II. Nat Prod Sci. 1997;3:19-28.
  12. Murata S, Ogawa K, Matsuzaka T, Chiba M, Nakayama K, Iwasaki K, et al. 1,8-Cineole ameliorates steatosis of pten liver specific KO mice via Akt inactivation. Int J Mol Sci. 2015;16:12051-63. https://doi.org/10.3390/ijms160612051
  13. Viollet B, Foretz M, Guigas B, Horman S, Dentin R, Bertrand L, et al. Activation of AMP-activated protein kinase in the liver: a new strategy for the management of metabolic hapatic disorders. J Physiol. 2006;574:41-53. https://doi.org/10.1113/jphysiol.2006.108506
  14. Smith BK, Marcinko K, Desjardins EM, Lally JS, Ford RJ, et al. Treatment of nonalcoholic fatty liver disease: role of AMPK. Am J Physiol Endocrinol Metab. 2016;311:730-40. https://doi.org/10.1152/ajpendo.00225.2016
  15. Kohijima M, Higuchi N, Kato M, Kotoh K, Yoshimoto T, Fujino T, et al. SREBP-1c, regulated by the insulin and AMPK signaling pathways, plays a role in nonalcoholic fatty liver disease. Int J Mol Med. 2008;21:507-11.
  16. Thomson DM, Winder WW. AMP-activated protein kinase control of fat metabolism in skeletal muscle. Acta Physiol. 2009;196:147-54. https://doi.org/10.1111/j.1748-1716.2009.01973.x
  17. Tolman KG, Dalpiaz AS. Treatment of non-alcoholic fatty liver disease. Ther Clin Risk Manaq. 2007;3:1153-63.
  18. Braunersreuther V, Viviani GL, Mach F, Montecucco F. Role of cytokines and chemokines in non-alcoholic fatty liver disease. World J Gastroenterol. 2012;18:727-35. https://doi.org/10.3748/wjg.v18.i8.727
  19. Lim DW, Kim H, Park JY, Kim JE, Moon JY, Park SD, Park WH. Amomum cardamomum L. ethyl acetate fraction protects against carbon tetrachloride-induced liver injury via an antioxidant mechanism in rats. BMC Complement Altern Med. 2016;16:155. https://doi.org/10.1186/s12906-016-1121-1
  20. Lim DW, Bose S, Wang JH, Choi HS, Kim YM, Chin YW, et al. Mofied SJH alleviates FFAs-induced hapatic steatosis through leptin signaling pathways. Sci Rep. 2017;7:45425. https://doi.org/10.1038/srep45425
  21. Min KJ, Cho KH, Kwon TK. The effects of oxidized low density lipoprotein (oxLDL)-induced heme oxygenase-1 on LPS-induced inflammation in RAW 264.7 macrophage cells. Cell Signal. 2012;24:1215-21. https://doi.org/10.1016/j.cellsig.2012.02.001
  22. Bekkering S, Quintin J, Joosten LA, van der Meer JW, Netea MG, Riksen NP. Oxidized low-density lipoprotein induces long-term proinflammatory cytokine production and foam cell formation via epigenetic reprogramming of monocytes. Arterioscler Thromb Vasc Biol. 2014;34:1731-8. https://doi.org/10.1161/ATVBAHA.114.303887
  23. Beltowski J. Statins and modulation of oxidative stress. Toxicol Mech Methods. 2005;15:61-92. https://doi.org/10.1080/15376520590918766
  24. Leamy AK, Eqnatchik RA, Young JD. Molecular mechanisms and the role of saturated fatty acids in the progression of non-alcoholic fatty liver disease. Prog Lipid Res. 2013;52:165-74. https://doi.org/10.1016/j.plipres.2012.10.004
  25. Boots AW, Haenen GR, Bast A. Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol. 2008;585:325-37. https://doi.org/10.1016/j.ejphar.2008.03.008
  26. Sultana B, Anwar F. Flavonols (kaempeferol, quercetin, myricetin) contents of selected fruits, vegetables and medicinal plants. Food Chem. 2008;108:879-84. https://doi.org/10.1016/j.foodchem.2007.11.053
  27. Lee KG, Shibamoto T, Takeoka GR, Lee SE, Kim JH, Park BS. Inhibitory effects of plant-derived flavonoids and phenolic acids on malonaldehyde formation from ethyl arachidonate. J Agric Food Chem. 2003;51:7203-7. https://doi.org/10.1021/jf0345447
  28. Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. 2002;109:1125-31. https://doi.org/10.1172/JCI0215593
  29. Kim JE. Tribulus terrestris suppresses the lipopolys accharide-induced inflammatory reaction in RAW264.7 macrophages through heme oxygenase-1 expression. Korean J Oriental Physiology & Pathology. 2014;28:63-8.
  30. Sikora JP, Chlebna-Sokol D, Krzyanska-Oberbek A. Proinflammatory cytokine (IL-6, IL-8), cytokine inhibitors (IL-6sR, STNFRII) and anti-inflammatory cytokines (IL-10, IL-13) in the pathogenesis of sepsis in newborns and infants. Arch Immunol Exp. 2001;49:399-404.

Cited by

  1. 사염화탄소로 유발된 산화적 손상에 대한 황칠나무 잎 추출물의 간세포 보호 효과 vol.30, pp.4, 2017, https://doi.org/10.5352/jls.2020.30.4.370