Food Science and Biotechnology

, Volume 28, Issue 1, pp 243–251 | Cite as

Orally administration of Neolentinus lepideus extracts attenuated ethanol induced accumulation of hepatic lipid in mice

  • Ki Moon Park
  • Ye Na Park
  • Oh Yun Kwon
  • Seung Ho LeeEmail author


In this study, we examined the effects of the water extract of Neolentinus lepideus (WENL), an edible mushroom, on ethanol-induced hepatic lipid accumulation. Ethanol-induced oil red O-positive spots on AML-12 hepatocytes were attenuated by WENL treatment. Furthermore, the oral administration of WENL in acute and chronic ethanol-fed mouse models resulted in the decrease in blood triglyceride and the accumulation of lipid droplets in the liver. Interestingly, the transcriptional expression related to lipid metabolisms, such as sterol regulatory element-binding protein 1, and cytochrome P450 2E1, was decreased by WENL treatment in both ethanol-induced AML-12 hepatocytes and our chronic ethanol-fed mouse models. In addition, WENL effectively attenuated the ethanol induced activation of MAP kinases and NF-κB in AML-12 hepatocytes. Taken together, our results suggested that WENL can be effective in alleviating alcohol-induced hepatic lipid accumulation and may be used as potential candidate for the prevention of alcoholic fatty liver disease.


Liver steatosis Neolentinus lepideus Hepatocytes cells Fatty liver 



This work was supported by the Rural Development Administration (PJ01022310), Korea.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Abdullah N, Ismail SM, Aminudin N, Shuib AS, Lau BF. Evaluation of Selected Culinary-Medicinal Mushrooms for Antioxidant and ACE Inhibitory Activities. Evid. Based Complement Alternat. Med. 2012: 464238 (2012)CrossRefGoogle Scholar
  2. Alberts AW, Strauss AW, Hennessy S, Vagelos PR. Regulation of synthesis of hepatic fatty acid synthetase: binding of fatty acid synthetase antibodies to polysomes. Proc. Natl. Acad. Sci. USA. 72: 3956–3960 (1975)CrossRefGoogle Scholar
  3. Bertola A, Mathews S, Ki SH, Wang H, Gao B. Mouse model of chronic and binge ethanol feeding (the NIAAA model). Nat. Protoc. 8: 627–637 (2013)CrossRefGoogle Scholar
  4. Brown MS, Goldstein JL. The SREBP pathway: regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell. 89: 331–340 (1997)CrossRefGoogle Scholar
  5. Cao YW, Jiang Y, Zhang DY, Zhang XJ, Hu YJ, Li P, Su H, Wan JB. The hepatoprotective effect of aqueous extracts of Penthorum chinense Pursh against acute alcohol-induced liver injury is associated with ameliorating hepatic steatosis and reducing oxidative stress. Food Funct. 6: 1510–1517 (2015)CrossRefGoogle Scholar
  6. Chang R. Functional properties of edible mushrooms. Nutr. Rev. 54: S91–S93 (1996)CrossRefGoogle Scholar
  7. Chen LY, Chen Q, Cheng YF, Jin HH, Kong DS, Zhang F, Wu L, Shao JJ, Zheng SZ. Diallyl trisulfide attenuates ethanol-induced hepatic steatosis by inhibiting oxidative stress and apoptosis. Biomed. Pharmacother. 79: 35–43 (2016)CrossRefGoogle Scholar
  8. Doskocil I, Havlik J, Verlotta R, Tauchen J, Vesela L, Macakova K, Opletal L, Kokoska L, Rada V. In vitro immunomodulatory activity, cytotoxicity and chemistry of some central European polypores. Pharm. Biol. 54: 2369–2376 (2016)CrossRefGoogle Scholar
  9. Ferre P, Foufelle F. Hepatic steatosis: a role for de novo lipogenesis and the transcription factor SREBP-1c. Diabetes Obes. Metab. 12 Suppl. 2: 83–92 (2010)CrossRefGoogle Scholar
  10. Friedman M. Mushroom Polysaccharides: Chemistry and Antiobesity, Antidiabetes, Anticancer, and Antibiotic Properties in Cells, Rodents, and Humans. Foods. 5 (2016)Google Scholar
  11. Gouillon Z, Lucas D, Li J, Hagbjork AL, French BA, Fu P, Fang C, Ingelman-Sundberg M, Donohue TM, Jr., French SW. Inhibition of ethanol-induced liver disease in the intragastric feeding rat model by chlormethiazole. Proc. Soc. Exp. Biol. Med. 224: 302–308 (2000)CrossRefGoogle Scholar
  12. Gramenzi A, Caputo F, Biselli M, Kuria F, Loggi E, Andreone P, Bernardi M. Review article: alcoholic liver disease–pathophysiological aspects and risk factors. Aliment. Pharmacol. Ther. 24: 1151–1161 (2006)CrossRefGoogle Scholar
  13. Han JY, Lee S, Yang JH, Kim S, Sim J, Kim MG, Jeong TC, Ku SK, Cho IJ, Ki SH. Korean Red Ginseng attenuates ethanol-induced steatosis and oxidative stress via AMPK/Sirt1 activation. J. Ginseng Res. 39: 105–115 (2015)CrossRefGoogle Scholar
  14. Hosoe T, Sakai H, Ichikawa M, Itabashi T, Ishizaki T, Kawai K. Lepidepyrone, a new gamma-pyrone derivative, from Neolentinus lepideus, inhibits hyaluronidase. J. Antibiot (Tokyo). 60: 388–390 (2007)CrossRefGoogle Scholar
  15. Ishihara A, Ide Y, Bito T, Ube N, Endo N, Sotome K, Maekawa N, Ueno K, Nakagiri A. Novel tyrosinase inhibitors from liquid culture of Neolentinus lepideus. Biosci. Biotechnol. Biochem. 82: 22–30 (2018)CrossRefGoogle Scholar
  16. Jarvelainen HA, Fang C, Ingelman-Sundberg M, Lukkari TA, Sippel H, Lindros KO. Kupffer cell inactivation alleviates ethanol-induced steatosis and CYP2E1 induction but not inflammatory responses in rat liver. J. Hepatol. 32: 900–910 (2000)CrossRefGoogle Scholar
  17. Kang L, Chen X, Sebastian BM, Pratt BT, Bederman IR, Alexander JC, Previs SF, Nagy LE. Chronic ethanol and triglyceride turnover in white adipose tissue in rats: inhibition of the anti-lipolytic action of insulin after chronic ethanol contributes to increased triglyceride degradation. J. Biol. Chem. 282: 28465–28473 (2007)CrossRefGoogle Scholar
  18. Kanuri G, Weber S, Volynets V, Spruss A, Bischoff SC, Bergheim I. Cinnamon extract protects against acute alcohol-induced liver steatosis in mice. J. Nutr. 139: 482–487 (2009)CrossRefGoogle Scholar
  19. Leung TM, Nieto N. CYP2E1 and oxidant stress in alcoholic and non-alcoholic fatty liver disease. J. Hepatol. 58: 395–398 (2013)CrossRefGoogle Scholar
  20. Li M, He Y, Zhou Z, Ramirez T, Gao Y, Gao Y, Ross RA, Cao H, Cai Y, Xu M, Feng D, Zhang P, Liangpunsakul S, Gao B. MicroRNA-223 ameliorates alcoholic liver injury by inhibiting the IL-6-p47phox-oxidative stress pathway in neutrophils. Gut. 66: 705–715 (2017)CrossRefGoogle Scholar
  21. Lu Y, Cederbaum AI. CYP2E1 and oxidative liver injury by alcohol. Free Radic. Biol. Med. 44: 723–738 (2008)CrossRefGoogle Scholar
  22. Lu Y, Zhuge J, Wang X, Bai J, Cederbaum AI. Cytochrome P450 2E1 contributes to ethanol-induced fatty liver in mice. Hepatology. 47: 1483–1494 (2008)CrossRefGoogle Scholar
  23. Ma Y, Xu L, Rodriguez-Agudo D, Li X, Heuman DM, Hylemon PB, Pandak WM, Ren S. 25-Hydroxycholesterol-3-sulfate regulates macrophage lipid metabolism via the LXR/SREBP-1 signaling pathway. Am. J. Physiol. Endocrinol. Metab. 295: E1369–E1379 (2008)CrossRefGoogle Scholar
  24. Macfarlane DP, Forbes S, Walker BR. Glucocorticoids and fatty acid metabolism in humans: fuelling fat redistribution in the metabolic syndrome. J. Endocrinol. 197: 189–204 (2008)CrossRefGoogle Scholar
  25. Mattila P, Konko K, Eurola M, Pihlava JM, Astola J, Vahteristo L, Hietaniemi V, Kumpulainen J, Valtonen M, Piironen V. Contents of vitamins, mineral elements, and some phenolic compounds in cultivated mushrooms. J. Agric. Food Chem. 49: 2343–2348 (2001)CrossRefGoogle Scholar
  26. Moreno MI, Isla MI, Sampietro AR, Vattuone MA. Comparison of the free radical-scavenging activity of propolis from several regions of Argentina. J. Ethnopharmacol. 71: 109–114 (2000)CrossRefGoogle Scholar
  27. Rendic S, Di Carlo FJ. Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab. Rev. 29: 413–580 (1997)CrossRefGoogle Scholar
  28. Siler SQ, Neese RA, Hellerstein MK. De novo lipogenesis, lipid kinetics, and whole-body lipid balances in humans after acute alcohol consumption. Am. J. Clin. Nutr. 70: 928–936 (1999)CrossRefGoogle Scholar
  29. Song BJ, Abdelmegeed MA, Henderson LE, Yoo SH, Wan J, Purohit V, Hardwick JP, Moon KH. Increased nitroxidative stress promotes mitochondrial dysfunction in alcoholic and nonalcoholic fatty liver disease. Oxid. Med. Cell Longev. 2013: 781050 (2013)CrossRefGoogle Scholar
  30. Tan X, Sun X, Li Q, Zhao Y, Zhong W, Sun X, Jia W, McClain CJ, Zhou Z. Leptin deficiency contributes to the pathogenesis of alcoholic fatty liver disease in mice. Am. J. Pathol. 181: 1279–1286 (2012)CrossRefGoogle Scholar
  31. Tong L. Acetyl-coenzyme A carboxylase: crucial metabolic enzyme and attractive target for drug discovery. Cell. Mol. Life Sci. 62: 1784–1803 (2005)CrossRefGoogle Scholar
  32. Ukawa Y, Furuichi Y, Kokean Y, Nishii T, Hisamatsu M. Effect of Hatakeshimeji (Lyophyllum decastes Sing.) Mushroom on serum lipid levels in rats. J. Nutr. Sci. Vitaminol (Tokyo). 48: 73–76 (2002)CrossRefGoogle Scholar
  33. Ukawa Y, Izumi Y, Ohbuchi T, Takahashi T, Ikemizu S, Kojima Y. Oral administration of the extract from Hatakeshimeji (Lyophyllum decastes Sing.) mushroom inhibits the development of atopic dermatitis-like skin lesions in NC/Nga mice. J. Nutr. Sci. Vitaminol (Tokyo). 53: 293–296 (2007)CrossRefGoogle Scholar
  34. Wada S, Yamazaki T, Kawano Y, Miura S, Ezaki O. Fish oil fed prior to ethanol administration prevents acute ethanol-induced fatty liver in mice. J. Hepatol. 49: 441–450 (2008)CrossRefGoogle Scholar
  35. Wasser SP. Medicinal mushrooms as a source of antitumor and immunomodulating polysaccharides. Appl. Microbiol. Biotechnol. 60: 258–274 (2002)CrossRefGoogle Scholar
  36. Xiao J, Wang J, Xing F, Han T, Jiao R, Liong EC, Fung ML, So KF, Tipoe GL. Zeaxanthin dipalmitate therapeutically improves hepatic functions in an alcoholic fatty liver disease model through modulating MAPK pathway. PLoS One. 9: e95214 (2014)CrossRefGoogle Scholar
  37. Yang L, Rozenfeld R, Wu D, Devi LA, Zhang Z, Cederbaum A. Cannabidiol protects liver from binge alcohol-induced steatosis by mechanisms including inhibition of oxidative stress and increase in autophagy. Free Radic. Biol. Med. 68: 260–267 (2014)CrossRefGoogle Scholar
  38. Yoon KN, Alam N, Lee KR, Shin PG, Cheong JC, Yoo YB, Lee TS. Antioxidant and antityrosinase activities of various extracts from the fruiting bodies of Lentinus lepideus. Molecules. 16: 2334–2347 (2011a)CrossRefGoogle Scholar
  39. Yoon KN, Lee JS, Kim HY, Lee KR, Shin PG, Cheong JC, Yoo YB, Alam N, Ha TM, Lee TS. Appraisal of Antihyperlipidemic Activities of Lentinus lepideus in Hypercholesterolemic Rats. Mycobiology. 39: 283–289 (2011b)CrossRefGoogle Scholar
  40. Zaidman BZ, Yassin M, Mahajna J, Wasser SP. Medicinal mushroom modulators of molecular targets as cancer therapeutics. Appl. Microbiol. Biotechnol. 67: 453–468 (2005)CrossRefGoogle Scholar

Copyright information

© The Korean Society of Food Science and Technology and Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  • Ki Moon Park
    • 1
  • Ye Na Park
    • 1
  • Oh Yun Kwon
    • 2
  • Seung Ho Lee
    • 2
    Email author
  1. 1.Department of Food Science and BiotechnologySungkyunkwan UniversitySuwonKorea
  2. 2.Department of Nano-BioengineeringIncheon National UniversityIncheonKorea

Personalised recommendations