Korean Journal of Food Science and Technology (한국식품과학회지)

Korean Society of Food Science and Technology (한국식품과학회)
권호 표지
DOI QR코드

DOI QR Code

Hepatoprotective effect of Ainsliaea acerifolia water extract on LPS/D-GalN-induced acute liver injury in human HepG2 cells

단풍취 열수 추출물의 HepG2 인간간세포의 LPS/D-Gal에 의해 유발된 급성 간 손상에 대한 간보호 효과

  • Lee, Sun-Yeop (Department of Research and Development, Chuncheon Bioindustry Foundation) ;
  • Han, Joon-Hee (Department of Research and Development, Chuncheon Bioindustry Foundation) ;
  • Choi, Da-Hye (Department of Research and Development, Chuncheon Bioindustry Foundation) ;
  • Hong, Min (Department of Research and Development, Chuncheon Bioindustry Foundation) ;
  • Kwon, Tae-Hyung (Department of Research and Development, Chuncheon Bioindustry Foundation) ;
  • Lee, Yong-Jin (Department of Research and Development, Chuncheon Bioindustry Foundation) ;
  • Yu, Keun-Hyung (Department of Research and Development, Chuncheon Bioindustry Foundation)
  • 이선엽 ((재)춘천바이오산업진흥원 기술개발실) ;
  • 한준희 ((재)춘천바이오산업진흥원 기술개발실) ;
  • 최다혜 ((재)춘천바이오산업진흥원 기술개발실) ;
  • 홍민 ((재)춘천바이오산업진흥원 기술개발실) ;
  • 권태형 ((재)춘천바이오산업진흥원 기술개발실) ;
  • 이용진 ((재)춘천바이오산업진흥원 기술개발실) ;
  • 유근형 ((재)춘천바이오산업진흥원 기술개발실)
  • Received : 2020.08.10
  • Accepted : 2020.09.06
  • Published : 2020.10.31
Download PDF
⟨ Previous Next ⟩

Abstract

This study investigated the antioxidant and hepatoprotective effects of Ainsliaea acerifolia water extract (AAWE) on HepG2 cells. Five types of caffeoylquinic acid (CQA) were detected in AAWE, namely, 4,5-di-O-caffeoylquinic acid (4,5-DCQA; 11.16 mg/g), 3,4-di-O-caffeoylquinic acid (3,4-DCQA; 5.23 mg/g), 5-O-caffeoylquinic acid (5-CQA; 4.88 mg/g), 3,5-di-O-caffeoylquinic acid (3,5-DCQA; 3.51 mg/g), and 4-O-caffeoylquinic acid (4-CQA; 3.31 mg/g). AAWE exerted ABTS+ antioxidant effects, evidenced by polyphenol content and 2,2'2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH radical scavenging) activities. AAWE (300 ㎍/mL) treatment significantly decreased the activities of gamma glutamyl transferase (GGT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) as compared to control and exerted protective effects against the increase in liver function index induced by lipopolysaccharide (LPS)/galactosamine (D-GalN) in HepG2 cells. In addition, the secretion of tumor necrosis factor (TNF)-α by HepG2 cells induced by LPS/D-GalN significantly increased in all treatment groups compared to that in the control. However, AAWE (100-300 ㎍/mL) treatment significantly decreased the secretion of TNF-α compared to that in the control. These results suggest that AAWE treatment reduces hepatotoxicity by increasing antioxidant activities, reducing GGT, AST, and LDH activities, and inhibiting TNF-α secretion.

본 연구에서는 간보호 활성이 우수한 것으로 알려진 단풍취의 활용가치를 높이고 향후 건강기능성식품 소재로써의 가능성을 알아보고자 LPS/D-GalN 독성유발에 따른 단풍취 열수 추출물의 간기능 개선효과를 연구하였다. 단풍취 열수 추출물 내에 존재하는 5종의 Caffeoylquinic acid (CQA) 분석결과 4,5-di-O-caffeoylquinic acid (4,5-DCQA) 11.16 mg/g, 3,4-di-O-caffeoylquinic acid (3,4-DCQA) 5.23 mg/g, 5-O-caffeoylquinic acid (5-CQA) 4.88 mg/g, 3,5-di-O-caffeoylquinic acid (3,5-DCQA) 3.51 mg/g 및 4-O-caffeoylquinic acid (4-CQA) 3.31 mg/g 순으로 나타났다. 단풍취 열수 추출물이 함유하고 있는 총 폴리페놀 함량은 74.03 mg/g이었으며, ABTS cation radical 소거능은 추출물의 농도 50, 100, 200 및 400 ㎍/mL의 범위에서 각각 12.2, 25.0, 40.8, 68.55%를 나타냈고 DPPH radical 소거능은 50 ㎍/mL의 농도에서 54.38%를 나타냈다. HepG2 세포에 LPS/D-GalN을 처리하여 간독성을 유발한 결과 정상군을 제외한 모든 처리군에서 GGT, AST 및 LDH 활성이 증가하였고, 단풍취 열수 추출물 300 mg/mL을 처리하였을 때 대조군과 비교하여 GGT, AST 및 LDH 활성이 유의적으로 감소하는 것으로 나타났다. LPS/D-GalN을 처리하였을 때 정상군과 비교하여 모든 처리군에서 TNF-α 분비가 유의적으로 증가하는 것을 확인 할 수 있었으며, 단풍취 열수 추출물을 100 ㎍/mL 이상 처리하였을 때 TNF-α의 분비가 유의하게 감소하였다. 이상의 결과로 볼 때 단풍취 열수 추출물은 항산화 활성 증가 및 GGT, AST, LDH의 활성을 감소시키고 TNF-α 분비를 억제시킴으로써 LPS/D-GalN으로 인한 간 손상을 예방하는 것으로 판단된다.

Keywords

References

  1. Blois MS. Antioxidant activity determination by the use of a stable free radical. Nature 181: 1199-1200 (1958) https://doi.org/10.1038/1811199a0
  2. Choi J, Park JK, Lee KT, Park KK, Kim WB, Lee JH, Jung HJ, Park HJ. In vivo antihepatotoxic effects of Ligularia fischeri var. spiciformis and the identification of the active component, 3,4-dicaffeoylquinic acid. J. Med. Food 8: 348-352 (2005) https://doi.org/10.1089/jmf.2005.8.348
  3. Choi SZ, Yang MC, Choi SU, Lee KR. Cytotoxic terpenes and lignans from the roots of Ainsliaea acerifolia. Arch. Pharm. Res. 29: 203-208 (2006) https://doi.org/10.1007/BF02969394
  4. Chojkier M, Fierer J. D-Galactosamine hepatotoxicity is associated with endotoxin sensitivity and mediated by lymphoreticular cells in mice. Gastroenterology 88: 115-121 (1985) https://doi.org/10.1016/S0016-5085(85)80142-6
  5. Farber JL, Gill G, Konishi Y. Prevention of galactosamine-induced liver necrosis by uridine. Am. J. Pathol. 72: 53-62 (1973)
  6. Keppler D, Lesch R, Reutter W, Decker K. Experimental hepatitis induced by D-galactosamine. Exp. Mol. Pathol. 9: 279-290 (1968) https://doi.org/10.1016/0014-4800(68)90042-7
  7. Lee EW, Kim TW, Kim HS, Park YM, Kim SH, Im MH, Kwak JH, Kim TH. Antioxidant and $\alpha$-glucosidase inhibitory effects of Ainsliaea acerifolia. Korean J. Food Preserv. 22: 275-280 (2015) https://doi.org/10.11002/kjfp.2015.22.2.275
  8. Lesch R, Reutter W, Keppler D, Decker K. Liver restitution after acute galactosamine hepatitis: autoradiographic and biochemical studies in rats. Exp. Mol. Pathol. 12: 58-69 (1969) https://doi.org/10.1016/0014-4800(70)90075-4
  9. Murakami T, Kim T, Nakamura H. Hepatitis, cirrhosis, and hepatoma. J. Magn. Reson. Imaging 8: 346-358 (1998) https://doi.org/10.1002/jmri.1880080214
  10. Nugroho A, Choi J, Song BM, Park HJ. Effect of Ainsliaea acerifolia extract on anti-acetylcholinesterase and peroxynitrite scavenging and analysis of caffeoylquinic acids. Korean J. Plant Res. 32: 270-274 (2019)
  11. Park, HJ. Chemistry and pharmacological action of caffeoylquinic acid derivatives and pharmaceutical utilization of chwinamul (Korean Mountainous vegetable). Arch. Pharm. Res. 33: 1703-1720 (2010) https://doi.org/10.1007/s12272-010-1101-9
  12. Park HJ, Nugroho A, Lee J, Kim JD, Kim WB, Lee KR, Choi JS. HPLC analysis of caffeoylquinic acids in the extract of Cacalia firma and peroxynitrite scavenging effect. Korean J. Pharmacogn. 40: 365-369 (2009)
  13. Park JY, Park CM, Kim JJ, Song YS. Hepatoprotective Activity of dandelion (Taraxacum officinale) water extract against D-galactosamine-induced hepatitis in rats. J. Korean Soc. Food Sci. Nutr. 37: 177-183 (2008) https://doi.org/10.3746/jkfn.2008.37.2.177
  14. Park SY, Kim GY, Jhoo JH. Protective Effect of 3,5-Dicaffeoylquinic Acid Isolated from Ligularia fischeri against Oxidative Damage in HepG2 Cells. J. Korean Soc. Food Sci. Nutr. 46: 1286-1292 (2017) https://doi.org/10.3746/jkfn.2017.46.11.1286
  15. Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic. Biol. Med. 26: 1231-1237 (1999) https://doi.org/10.1016/S0891-5849(98)00315-3
  16. Sakaguchi T, Nakamura S, Suzuki S, Oda T, Ichiyama A, Baba S, Okamoto T. Participation of platelet-activating factor in the lipopolysaccharide-induced liver injury in partially hepatectomized rats. Hepatology 30: 959-967 (1999) https://doi.org/10.1002/hep.510300414
  17. Seo MG, Kang YM, Chung KS, Cheon SY. Anti-inflammatory Effects of Ethanol Extract of Various Korean Compositae Herbs in LPS-induced RAW 264.7 Macrophages Kor. J. Herbol. 32: 17-24 (2017)
  18. Seo MG. Anti-inflammatory effects of Ainsliaea acerifolia in LPSinduced Raw 264.7 macrophages. MS Thesis, Sangji University, Korea, p 9-10 (2017)
  19. Suzuki S, Nakamura S, Serizawa A, Sakaguchi T, Konno H, Muro H, Kosugi I, Baba S. Role of Kupffer cells and the spleen in modulation of endotoxin-induced liver injury after partial hepatectomy. Hepatology 24: 219-225 (1996) https://doi.org/10.1002/hep.510240135
  20. Yoon US. Anti-obesity effect of Maple-leaf Ainsliaea (Ainsliea acerifolia Sch.Bip). MS Thesis, Andong University, Korea, p 35-40 (2018)
  21. Yu KH, Lee SY, Yang HM, Ham HA, Lee SU, Chae SW, Lee YJ. Effect of fermented water extracts from Ligularia fischeri on hepatotoxicity induced by D-galactosamine in rats. J. Korean Soc. Food Sci. Nutr. 44: 1422-1430 (2015) https://doi.org/10.3746/jkfn.2015.44.10.1422
  22. Zhao Y, Zhao J, Li XP, Zhou CX, Sun HD, Hao XJ, Xiao PG. Advances in caffeoylquinic acid research. Zhongguo Zhong Yao Za Zhi 31: 869-874 (2006)