DOI QR코드

DOI QR Code

Effect of Fermented Water Extracts from Ligularia fischeri on Hepatotoxicity Induced by D-Galactosamine in Rats

D-Galactosamine 투여 랫트에서 곰취 열수 추출 발효물이 간 독성 저하에 미치는 영향

  • Yu, Keun-Hyung (Department of Technical Development Chuncheon Bioindustry Foundation) ;
  • Lee, Sun-Yeop (Department of Technical Development Chuncheon Bioindustry Foundation) ;
  • Yang, Hyun-Mo (Department of Technical Development Chuncheon Bioindustry Foundation) ;
  • Ham, Young-Ahn (Department of Technical Development Chuncheon Bioindustry Foundation) ;
  • Lee, Soo-Ung (Department of Technical Development Chuncheon Bioindustry Foundation) ;
  • Chae, Seoung-Wan (Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine) ;
  • Lee, Yong-Jin (Department of Technical Development Chuncheon Bioindustry Foundation)
  • 유근형 ((재)춘천바이오산업진흥원 기술개발실) ;
  • 이선엽 ((재)춘천바이오산업진흥원 기술개발실) ;
  • 양현모 ((재)춘천바이오산업진흥원 기술개발실) ;
  • 함영안 ((재)춘천바이오산업진흥원 기술개발실) ;
  • 이수응 ((재)춘천바이오산업진흥원 기술개발실) ;
  • 채승완 (성균관대학교 의과대학 강북삼성병원 병리과) ;
  • 이용진 ((재)춘천바이오산업진흥원 기술개발실)
  • Received : 2015.06.19
  • Accepted : 2015.08.10
  • Published : 2015.10.31

Abstract

This study was conducted to determine the effect of fermented water extracts from Ligularia fischeri (LAF) on reduction of hepatotoxicity induced by D-galactosamine (D-GalN) in rats. In this experiment, male Sprague-Dawley rats were used as experimental animals, which were divided into eight groups: normal group, D-GalN-treated group (control), D-GalN and non-fermented water extracts from Ligularia fischeri (LA)-treated groups [100, 200, and 400 mg/kg BW (body weight)], and D-GalN and LAF-treated groups (100, 200, and 400 mg/kg BW). ${\gamma}$-Glutamyl transferase, aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase activities in serum of the D-GalN and LAF-treated groups decreased significantly compared to those of the control group (P<0.05). The high density lipoprotein-cholesterol levels of the D-GalN and LAF-treated groups increased significantly compared to those of the control group (P<0.05). The low density lipoprotein-cholesterol and triglyceride levels of the D-GalN and LAF-treated groups decreased significantly compared to those of the control group (P<0.05). The atherogenic index values of the D-GalN and LAF-treated groups decreased significantly compared to those of the control group (P<0.05), and their high density lipoprotein cholesterol by total cholesterol ratio increased significantly in these groups (P<0.05). Superoxide dismutase activity of liver tissues were enhanced significantly (P<0.05) in the D-GalN and LAF-treated groups compared to that of the control group (P<0.05), whereas their malondialdehyde content decreased significantly in these groups (P<0.05). The histopathological observations revealed apoptotic cells and mild portal inflammation in liver tissues of the D-GalN and LAF-treated groups. Taken together, these results demonstrate that LAF may improve plasma lipid profile and alleviate hepatic damage.

본 연구는 산채류 중 널리 섭취되고 있는 곰취의 활용가치를 높이고 건강기능식품 소재로써의 가능성을 확인고자 DGalN 동물모델을 통해 곰취 열수 추출 발효물의 간 기능 개선 효과를 연구하였다. 실험기간 동안 실험동물의 체중 증가량은 처리군 간 유의적인 차이가 없었으며(P>0.05), 간 무게는 곰취 열수 추출물 투여군에서 유의하게 증가하는 것으로 나타났다(P<0.05). 혈청 중 GGT 분석 결과 곰취 열수 추출물과 발효물 투여군에서 대조군과 비교하여 유의하게 감소하였다(P<0.05). 특히 발효물 투여군의 경우 GGT, AST, ALT 및 LDH의 효소 활성이 대조군과 비교하여 40% 이상 감소하였다(P<0.05). 총 콜레스테롤의 함량을 측정한 결과 정상식이군과 비교하여 모든 투여군에서 유의하게 감소하였으며(P<0.05), HDL-콜레스테롤의 경우 발효물 투여군에서 대조군과 비교하여 유의하게 증가하였다(P<0.05). LDL-콜레스테롤은 농도 의존적으로 유의하게 감소하였다(P<0.05). 중성지방의 함량은 발효물 투여군에서 대조군과 비교하여 유의하게 감소하였으며(P<0.05), 총 콜레스테롤 함량 중 HDL-콜레스테롤 함량의 비율은 발효물 투여군에서 대조군과 비교하여 유의하게 증가하는 것으로 나타났고(P<0.05), 동맥경화지수의 경우 발효물 투여군에서 대조군과 비교하여 유의하게 감소하였다(P<0.05). 발효물의 경우 SOD 활성이 유의하게 증가하였으며(P<0.05), 간 조직 내 과산화지질의 분해산물인 MDA 함량은 곰취 열수 추출물 및 발효물 투여군에서 대조군과 비교하여 MDA 함량이 유의하게 감소하였다(P<0.05). 간 조직 병리학적 분석 결과 곰취 열수 추출물 및 발효물 투여군에서 대조군과 비교하여 세포사멸사 지수, 문맥엽 염증 지수 등이 개선되는 경향을 보였으나 유의적인 차이는 없는 것으로 나타났다(P>0.05). 이상의 결과로 보아 곰취 열수 추출 발효물이 간 기능 효소의 활성 억제, 혈청지질 대사 개선, 간 조직 내 SOD 활성증가 및 과산화지질을 감소시켜 D-GalN으로 인한 간 손상을 완화시키는 데 효과적일 것으로 사료되며, 향후 건강기능 식품 소재로 이용 가능할 것으로 판단된다.

Keywords

References

  1. Kim SM, Kang SW, Um BH. 2010. Extraction conditions of radical scavenging caffeoylquinic acids from Gomchui (Ligularia fischeri) tea. J Korean Soc Food Sci Nutr 39: 399-405. https://doi.org/10.3746/jkfn.2010.39.3.399
  2. National Rural Living Science Institute. 1996. Food composition table. 5th ed. National Rural Living Science Institute, Suwon, Korea. p 86.
  3. Cho SD, Kim GH. 2005. Food product development and quality characteristics of Ligularia fischeri for food resources. Korean J Food Preserv 12: 43-47.
  4. Bae JH, Yu SO, Kim YM, Chon SU, Kim BW, Heo BG. 2009. Physiological activity of methanol extracts from Ligularia fischeri and their hyperplasia inhibition activity of cancer cell. J Bio-Environment Control 18: 67-73.
  5. Ham SS, Lee SY, Oh DH, Jung SW, Kim SH, Chung CK, Kang IJ. 1998. Antimutagenic and antigenotoxic effects of Ligularia fischeri extracts. J Korean Soc Food Sci Nutr 27: 745-750.
  6. Na Y, Kim JH, Sim GS, Lee BC, Pyo HB. 2006. Effect of antioxidation and inhibition of matrix metalloproteinase-1 from Ligularia fischeri. J Soc Cosmet Scientists Korea 32: 129-134.
  7. Choi EM. 2007. Ligularia fischeri leaf extract prevents the oxidative stress in DBA/1J mice with type II collagen-induced arthritis. J Appl Toxicol 27: 176-182. https://doi.org/10.1002/jat.1190
  8. Jeong S, Kim E, Hwangbo H, Ham S. 1998. Effects of Ligularia fischeri extracts on oxidation of low density lipoprotein. Korean J Food Sci Technol 30: 1214-1221.
  9. Choi EM, Ding Y, Nguyen HT, Park SH, Kim YH. 2007. Antioxidant activity of Gomchi (Ligularia fischeri) leaves. Food Sci Biotechnol 16: 710-714.
  10. Lee JH, Chi SC, Kim SH, Shin YH, Choi J. 2005. Protective effect of DWP-04 against hepatotoxicity induced by Dgalactosamine. Life Sci 15: 461-467. https://doi.org/10.5352/JLS.2005.15.3.461
  11. Murakami T, Kim T, Nakamura H. 1998. Hepatitis, cirrhosis, and hepatoma. J Magn Reson Imaging 8: 346-358. https://doi.org/10.1002/jmri.1880080214
  12. Keppler D, Lesch R, Reutter W, Decker K. 1968. Experimental hepatitis induced by D-galactosamine. Exp Mol Pathol 9: 279-290. https://doi.org/10.1016/0014-4800(68)90042-7
  13. Farber JL, Gill G, Konishi Y. 1973. Prevention of galactosamine-induced liver necrosis by uridine. Am J Pathol 72: 53-62.
  14. Decker K, Keppler D. 1974. Galactosamine hepatitis: key role of the nucleotide deficiency period in the pathogenesis of cell injury and cell death. Rev Physiol Biochem Pharmacol 71: 77-106.
  15. Wang JF, Wendel A. 1990. Studies on the hepatotoxicity of galactosamine/endotoxin or galactosamine/TNF in the perfused mouse liver. Biochem Pharmacol 39: 267-270. https://doi.org/10.1016/0006-2952(90)90025-G
  16. El-Mofty SK, Scrutton MC, Serroni A, Nicolini C, Farber JL. 1975. Early, reversible plasma membrane injury in galactosamine-induced liver cell death. Am J Pathol 79: 579-595.
  17. Chojkier M, Fierer J. 1985. D-Galactosamine hepatotoxicity is associated with endotoxin sensitivity and mediated by lymphoreticular cells in mice. Gastroenterology 88: 115-121. https://doi.org/10.1016/S0016-5085(85)80142-6
  18. Lesch R, Reutter W, Keppler D, Decker K. 1969. Liver restitution after acute galactosamine hepatitis: autoradiographic and biochemical studies in rats. Exp Mol Pathol 12: 58-69.
  19. Han EK, Jin YX, Yoo YS, Jung EJ, Lee JY, Chung CK. 2009. Effect of Artemisia capillaris and Paecilomyces japonica on the reduction of hepatotoxicity and lipid metabolism induced by ethanol. J Korean Soc Food Sci Nutr 38: 1016-1023. https://doi.org/10.3746/jkfn.2009.38.8.1016
  20. McCord JM, Fridovich I. 1969. Superoxide dismutase. An enzymatic function for erythrocuprein (hemocuprein). J Biol Chem 244: 6049-6055.
  21. Troncoso Brindeiro CM, Lane PH, Carmines PK. 2012. Tempol prevents altered $K^+$ channel regulation of afferent arteriolar tone in diabetic rat kidney. Hypertension 59: 657-664. https://doi.org/10.1161/HYPERTENSIONAHA.111.184218
  22. Gove ME, Rhodes DH, Pini M, van Baal JW, Sennello JA, Fayad R, Cabay RJ, Myers MG Jr, Fantuzzi G. 2009. Role of leptin receptor-induced STAT3 signaling in modulation of intestinal and hepatic inflammation in mice. J Leukoc Biol 85: 491-496.
  23. Choi J, Park JK, Lee KT, Park KK, Kim WB, Lee JH, Jung HJ, Park HJ. 2005. In vivo antihepatotoxic effects of Ligularia fischeri var. spiciformis and the identification of the active component, 3,4-dicaffeoylquinic acid. J Med Food 3: 348-352.
  24. Yoo JH, Oidovsambuu S, Kim SM, Jeon NR, Yun JH, Kang K, Jho EH, Lee SB, Nho CW. 2011. Hepatoprotective effect of Handaeri-gomchi (Ligularia fischeri var. spiciformis Nakai) extract against chronic alcohol-induced liver damage in rats. Food Sci Biotechnol 20: 1655-1661. https://doi.org/10.1007/s10068-011-0228-x
  25. Shang YF, Kim SM, Song DG, Pan CH, Lee WJ, Um BH. 2010. Isolation and identification of antioxidant compounds from Ligularia fischeri. J Food Sci 75: C530-C535. https://doi.org/10.1111/j.1750-3841.2010.01714.x
  26. Thurman RG, Bradford BU, Iimuro Y, Knecht KT, Connor HD, Adachi Y, Wall C, Arteel GE, Raleigh JA, Forman DT, Mason RP. 1997. Role of Kupffer cells, endotoxin and free radicals in hepatotoxicity due to prolonged alcohol consumption: studies in female and male rats. J Nutr 127: 903S-906S.
  27. Nordmann R, Ribiere C, Rouach H. 1992. Implication of free radical mechanisms in ethanol-induced cellular injury. Free Radic Biol Med 12: 219-240. https://doi.org/10.1016/0891-5849(92)90030-K
  28. Jeon SM, Bok SH, Jang MK, Lee MK, Nam KT, Park YB, Rhee SJ, Choi MS. 2001. Antioxidative activity of naringin and lovastatin in high cholesterol-fed rabbits. Life Sci 69: 2855-2866. https://doi.org/10.1016/S0024-3205(01)01363-7
  29. Moon SH, Lee MK, Chae KS. 2001. Inhibitory effects of the solvent fractions from persimmon leaves on xanthine oxidase activity. Korean J Food & Nutr 14: 120-125.
  30. de Haan JB, Cristiano F, Iannello RC, Kola I. 1995. Cu/Zn-superoxide dismutase and glutathione peroxidase during aging. Biochem Mol Biol Int 35: 1281-1297.
  31. Byers T, Perry G. 1992. Dietary carotenes, vitamin C, and vitamin E as protective antioxidants in human cancers. Annu Rev Nutr 12: 135-159.
  32. Lawrence RA, Burk RF. 1976. Glutathione peroxidase activity in selenium-deficient rat liver. Biochem Biophys Res Commun 71: 952-958. https://doi.org/10.1016/0006-291X(76)90747-6

Cited by

  1. Effect of Angelica keiskei Koidzumi Extract on Alcohol-Induced Hepatotoxicity In Vitro and In Vivo vol.45, pp.10, 2016, https://doi.org/10.3746/jkfn.2016.45.10.1391
  2. 아이스플랜트(Mesembryanthemum crystallinum L.) 발효추출물의 항산화, 항당뇨 및 간 보호효과 vol.27, pp.8, 2017, https://doi.org/10.5352/jls.2017.27.8.909
  3. Efficacy of Artemisia annua L. extract for recovery of acute liver failure vol.8, pp.7, 2015, https://doi.org/10.1002/fsn3.1662
  4. Forsythia Fruit Prevents Fulminant Hepatitis in Mice and Ameliorates Inflammation in Murine Macrophages vol.13, pp.8, 2021, https://doi.org/10.3390/nu13082901