The Studies on Search of Antifibrotic Effect by Several Herbs Extract in Rat Liver Tissue

수종(數種)의 한약재(韓藥材) 전탕액(煎湯液)이 동물 간조직내 항섬유효능검색에 관한 실험적 연구

  • Seo Dong-Jin (Dept. of Preventive Medicine, College of Oriental Medicine, Wonkwang University) ;
  • Lee Chun-Woo (Dept. of Preventive Medicine, College of Oriental Medicine, Wonkwang University) ;
  • Kim Hong-Gi (Dept. of Preventive Medicine, College of Oriental Medicine, Wonkwang University) ;
  • Lee Ki-Nam (Dept. of Preventive Medicine, College of Oriental Medicine, Wonkwang University)
  • 서동진 (원광대학교 한의과대학 예방의학교실) ;
  • 이춘우 (원광대학교 한의과대학 예방의학교실) ;
  • 김홍기 (원광대학교 한의과대학 예방의학교실) ;
  • 이기남 (원광대학교 한의과대학 예방의학교실)
  • Published : 2001.06.29

Abstract

Antifibrotic drugs could be delayed or inhibited massive collagen deposition in liver tissue or inhibited collagen synthesis. we investigated antifibrotic effects by several herbs(Schisnadra chinensis, Ganoderma japonicum, Sedum sarmentosum, Alisma canaliculatum, Plantago asiatica) extract with observations of collagen accumulation in liver tissue and collagen synthesis in sera. Rats were used for experimental animal that were devided 3 groups(sham control, BDL/S, BDL/S-ER). Rats were operated for inducing liver fibrosis(cirrhosis) by bile duct obstruction. Several herbs were prepared by water extraction and were applicated p. o. $3ml/day$ during 4 weeks. After observation period, rats were sacrificed and liver tissue and sera were collected. In result, the mortality of rats was 35% in BDL/S group and 20% in BDL/S-ER The color of bile juice in BDL/S-ER was bright yellow and murky yellow in BDL/S group. The significantly lower weight of liver($16.21g{\pm}5.3,\;20.58{\pm}2.4$) and spleen($1.96g{\pm}0.96,\;3.93{\pm}0.21$) were shown in BDL/S-ER than that of BDL/S(p<0.05) group. The value of collagen in liver tissue(25.7%) in BDL/S-ER was observed significantly lower than that of BDL/S group (Tab. 2). AST. ALT, ALP, t-bilirubin, BUN levels were low in BDL/S-ER as compared with those of BDL/S group, but the significance was not proven. The trichrome stained liver tissue in BDL/S-ER group was observed mild bile duct proliferation and fibrosis compared with BDL/S group. In conclusion, natural products inhibited new collagen synthesis and delayed massive collagen deposition in liver tissue, so that they have noticeable antifibrotic effects in experimental liver fibrosis(cirrhosis).

Keywords

References

  1. 東醫肝系內科學 金定濟(外)
  2. 中醫內科學 上海中醫學院(編)
  3. 鍼灸經緯 楊維傑
  4. 中醫學基礎 北京中醫學院(編)
  5. 景岳全書 張介賓
  6. 金궤要略釋文 v.下冊 湖北中醫學院(編)
  7. 中藥大辭典 v.下冊 江蘇新醫學院
  8. 黃帝內徑 張隱庵馬元臺合註
  9. 東醫寶鑑 許俊
  10. 慶熙韓醫大論文集 v.5 生肝健脾湯이 肝臟의 代謝와 再生機能에 미치는 影響 金秉雲(外)
  11. 慶熙韓醫大論文集 v.1 茵蔯五령散이 肝疾患治療 效果에 關한 硏究 金光湖(外)
  12. 慶熙韓醫大論文集 v.2 百消丸 및 加味百消丸이 四鹽化炭素로 인한 白? 肝損傷에 미치는 影響에 關하여 文준典
  13. Disease of the liver and biliary system Sherlock, S.
  14. New Eng J Med v.324 no.14 Transforming growth factors ${\bata}$1 and ${\alpha}$ in chronic liver disease Castilla, A.;Prieto, J.;Fausto, N.
  15. 類證治威 林佩琴
  16. 丹溪心法 朱丹溪
  17. N. Engl. J. Med. v.312 Trial of penicillamine in advanced primary biliary cirrhosis Dickson, E.R.;Flemming, T.R.;Wiesner, R.H.;Baldus, W.P.
  18. GUT v.26 Double blind controlled trial of d-penicillamine in patients with primary biliary cirrhosis Neubauer, J.;Cristensen, E.;Portmann, B.;Caballeri, J.;Rodes, J.;Ranek, L.
  19. Hepatol v.7 A controlled clinical trial evaluating cyclosporin in the treatment of primary biliary cirrhosis: A preliminary report Wiesner, R.M.;Dickson, E.R.;Lindor, D.;Jorgensen, R.;LaRusso, N.F.;Baldus, W.
  20. Hepatol v.10 Ettect of ursodeoxycholic acid on bile acid metabolism in primary biliary cirrhosis Batta, A.K.;Saken, G.;Arora, R.;Sheffer, S.
  21. Z. Allg. Med. v.71 Chronische Hepatitis-Antifibrotische Therapieausaetze Schuppan, D.
  22. Liver v.4 Steroid treatment lowers hepatic fibroplasis, as explored by serum aminoterminal procollagen III peptide in chronic liver disease Ballardini, G.;Faccani, A.;Bianchi, F.B.(et al.)
  23. J. Hepatol v.14 Immunosuppressive therapy for primary biliary cirrhosis Beukers, R.;Schalm, S.W.
  24. Biochem Biophys Res Comm v.167 no.2 Niacin prevents DNA strand breakage by adenosine deaminase inhibitor Weitberg, A.B.;Corvese, D.
  25. Hepatol v.16 Vitamin E dietary supplementation protects against carbon tetrachloride-induced chronic liver damage and cirrhosis Parola, M.;Leonarduzzi, G.;Biasi, F.;Albano, E.;Biocca, M.E.;Poli, G.;Dianzani, M.U.
  26. J. Hepatol v.17 Effects of terlipression on hemodynamics and oxygen content in conscious portal vein stenosed and cirrhotic rats receiving propranolol Lebrc, D.;Moreau, R.;Cailmail, S.;Sogni, P.;Oberti, F.;Hadengue, A.
  27. Hepatol v.19 Protective effect of the lazaroid U74006F in cold ischemia-reperfusion injury of the liver Cosenza, C.A.;Cramer, D.V.;Cunneen, S.A.;Tuso, P.J.;Wang, H.K.;Makowka, L.
  28. Prog. Med. v.88 Serum variation of 2 markers of fibrogenesis in chronic hepatitis C treated with alfa interferon Soresi, M.;Bascone, F.;Agate, V.;Carroccio, A.;Barresi, E.;Cartabellota, A.;Montalto, G.
  29. Hepatol v.10 no.5 ${\gamma}$-interferon treatment inhibits collagen deposition in murine schistosomiasis Craja, M.J.;Weiner, F.R.;Takahashi, S.;Giambrone, M.A.(et al.)
  30. J. Clin. Invest. v.79 Gamma interferon inhibits collagen synthesis in vivo in the mouse Granstein, R.D.;Murphy, G.F.;Margolis, R.J.
  31. J. Hepatology v.13 Beneficial effects of inhibitors of prolyl 4-hydroxylase in CCl4-induced fibrosis of the in rats Bickel, M.;Baader, E.;Brocks, D.G.;Engelhart, K.
  32. Hepatol. v.18 The immunosuppressive effect of ursodeoxycholic acid: Acomparative in vitro study on human peripheral blood mononuclear cells Lacaille, F.;Paradis, K.
  33. N. Engl. J. Med. v.324 The UDCA-PBC study group. Multicenter controlled trials of ursodiol for the treatment of primary biliary cirrhosis Poupon, R.E.;Balkau, B.;Eschwege, E.;Poupon, R.
  34. Hepatol v.16 Ursodeoxycholic acid therapy in cystic fibrosis-associated liver disease Colombo, C.;Crosignani, A.;Assaisso, M.;Maria Battezzati, P.;Podda, M.;Giunta, A.;Zimmer-Nechemias, Z.;Setchell, K.
  35. Hepatol v.26 no.3 Silymarin retards collagen accumulation in early and advanced biliary fibrosis secondary to complete bile duct obliteration in rats Boigk, G.;Stroedter, L.;Herbst, H.;Wakdschmidt, J.;Riecken, E.O.;Schuppan, D.
  36. J Hepatol v.18 New challengers in hepatic firosis Clement, B.;Loreal, O.;Levavasseur, F.;Cuillouzo, A.
  37. Anal. Biochem. v.112 A single method to determine nanogram levels of 4-hydroxyproline in biological tissue Jamall, I.S.;Finelli, V.N.
  38. 병리학회지 v.24 간경변증의 원인적 분류와 형태학적 특성 한은경;박찬일;이상인
  39. 사망원인통계연보 경제기획원
  40. 한국인의 건강수준 보건복지부
  41. Kor J Pathol v.25 Morphormetric analysis of cirrhotic nodules in hepatocellular carcinoma-bearing livers Kang, K.H.;Kim, Y.I.
  42. 간질환의 병리 박찬일;김호근;이유복
  43. Leber, Magen Darm v.8 Die Leberfibrose - Entstehung, Dynamik und klinische Bedeutung Popper, H.
  44. Sem in Liver Disease v.10 no.1 Structure of the extracellular matrix in normal and fibrotic liver; collagens and glycoproteins Schuppan, D.
  45. J Hepatol v.13 Connective tissue polypeptides in serum as parameters to monitor antifibrotic treatment in hepatic fibrogenesis Schuppan, D.
  46. J Hepatol v.17 Hypotension in experimental cirrhosis: Is loss of vascular responsiveness to norepinephrine the cause of hypotension in chronic bile-duct-ligated dogs? Bomzon, A.;Binah, O.;Blendis, L.M.
  47. JAVMA v.199 Evaluation of tewlve-hour preprandial and two-hour postprandial serum bile acids concentrations for diagnosis of hepatobiliary disease in dogs Center, S.A.;ManWarren, T.;Slater, M.R.;Wilentz, E.
  48. Vet Rec v.133 Idiopathic hepatic fibrosis in 15 dogs Rutgers, H.C.;Haywood, S.;Kelly, D.
  49. JAVMA v.205 hylouse ascites in cats: Nine cases(1978-1993) Gores, B.R.;Berg, J.;Carpenter, J.L.;Ullman, S.L.
  50. Z. Gastroenterologie v.20 Procollagen-type III-peptide serum concentrations in chronic persistant and chronic active hepatitis and i cirrhosis of the liver and their diagnostic value Raedsch, R.;Stiehl, A.;Waldherr, R.;Mall, G.;Gmelin, K.;Gotz, R.;Walker, S.;Czygan, P.;Kommerell, B.
  51. Gut v.34 Serum concntration of laminin in cirhosis of the liver Collazos, J.;Diaz, F.;Genolla, J.
  52. Clin. Biochem. v.24 no.3 Biochemical markers of hepatic fibrosis Plebani, M.;Burlina, A.
  53. Gastroenterol v.98 no.6 Markers of fibrogenesis and basement membrane formation in alcoholic liver disease. Relation to severity, presence of hepatitis, and alcohol intake Niemela, O.;Risteli, J.;Blake, J.E.;Risteli, L.;Compton, K.V.;Orrego, H.
  54. Gastroenterol v.90 Serum procollagen type III peptide as marker of hepatic fibrogenesis in alcoholic hepatitis Torres-Salines, M.;Pares, A.;Cabeleria, J.;Jimez, W.
  55. Ann. Clin. Biochem. v.34 A comparison of four serum markers of rfibrosis in the diagnosis of cirrhosis Fabis, C.;Federico, E.;Toniutto;Pirisi M.
  56. Clin Biochem v.25 no.6 Clinical significance of serum 7S collagen in various liver diseases Yamada, S.;Suou, T.;Kawasaki, H.;Yoshikawa, N.
  57. J. Gastroenterol. Hepatol v.11 no.11 Aminoterminal propeptide of type III procollagen and hyaluronan in patients with primary biliary cirrhosis: markers of fibrosis in primary biliary cirrhosis Remmel, T.;Remmel, H.;Salupere, V.
  58. J. Gastroenterol. v.32 no.3 Noninvasive determination of liver collagen content in chronic hepatitis as variables Takamatsu, S.;Nakabayashi, H.;Okamotm Y.;Nakano, H.
  59. J. Gastroenterol. Hepatol. v.5 no.6 Diagnostic and prognostic value of the determination of the aminopropeptide of type III procollagen in patients with primary liver cancer Farinati, F.;Annoni, G.;Donato, M.F.;Nardelli, P.;Bertozzo, A.;De Maria, N.;Zotti, S.;Salvagnini, M.;Martinez, D.;Naccarato, R.
  60. J Gastroenterol Hepatol v.11 Serum markers for fibrosis and plasma transforming growth factor-beta 1 in patients with hepatocellular carcinoma in comparison with patients with liver cirrhosis Murawaki, Y.;Ikuta, Y.;Nishimura, Y.;Koda, M.;Kawasaki, H.
  61. Hepatol v.5 A radioimmunoassay procedure for type III procollagen: Its use in the detection of hepatic fibrosis Galambos, M.R.;Collins, D.C.;Galambos, J.T.
  62. Hepatol v.10 The intergrated value of serum procollagen type III peptice over time hepatic hydroxyproline content and stainable collagen in a model dietry cirrhosis in the rat Ruwart, M.J.;Wilkinson, K.F.;Rush, B.D.;Kim, K.Y.;Schuppan, D.
  63. J Biolchem v.262 Increased procollagen mRNA levels in carbon tetrachloride-induced liver fibrosis in rats Pierce, R.A.;Glaug, M.R.;Greco, R.S.;Mackenzie, J.W.;Boyd, C.D.;Deak, S.B.
  64. Biochem. J v.249 Serum concentrations of the N-terminal propeptide of type III procollagen and two type IV collagen fragments and gene expression of the respective collagen types in liver in rats with dimethylnitrosamine induced hepatic fibrosis Savolainen, E.R.;Brocks, D.;Ala-Kokko, L.;Kivirikko, K.
  65. Hepatol v.24 Changes in serum fibrogenesis markers during interferon therapy for chronic hepatitis type C Ishibashi, K.;Kashiwage, T.;Ito, A.;Nagasawa, M.;Tomaya, T.;Ozaki, S.;Naito, M.;Azuma, M.
  66. Chung Kuo Chung Hsi I Chieh Ho Tsa Chih v.15 no.10 Preliminary study on early fibrosis of chronic hepatitis B treated with Ginkgo biloba Composita Li, W.;Dai, Q.T.;Liu, Z.E.
  67. Yakhak Hoeji v.38 The antifibrotic effects of polysaccharides extracted from Gornoderma lucidum on the experimental hepatic cirrhosis Park, U.J.;Kim, K.Y.;Kim, J.B.;Kim, S.Y.;Lee, S.Y.;Sohn, D.W.
  68. Jpn. J. Pharmacol v.70 no.1 Effects of the mycelial extract of cultured cordyceps sinensis on in vivo hepatic energy metabolism in the mouse Manabe, N.;Sugimoto, M.;Azuma, Y.;Takemoto, N.;Yamashita, A.
  69. 藥學會紙 v.3 The andtifibrotic effects of poly- saccharides extracted from Gornoderma lucidum on tyhe experimental hepatic cirrhosis 박은전;김기영;손동환;김재백
  70. 원광대학교 약품연구소보 v.7 Biliary liver fibrosis 實驗東物에서 인삼, 영지, 오미자의 항섬유화 약효검색 김기영;한상수;김재백
  71. Hepatol v.24 A randomized trial comparing colchicine and ursodesoxycholic acid combination to ursodesoxycholic acid in primary biliary cirrhosis Poupon, R.E.;Huet, P.M.;Poupon, R.;Bonnand, A.M.;Nhieu, J.T.;Zafrani, E.S.
  72. 신씨본초학 신길구
  73. 임상본초학 신민교
  74. 동양의학대사전 전통의학연구소(編)
  75. 한방의약대사전 진존인
  76. The pharmacology of Chinese Herbs Huang, Kee-Chang
  77. Chinese Drugs of plant Origin Tang, W.;Eisenbrand, G.
  78. Natl Med. J. China v.54 Efect on increased SGPT (serum glutamic pyruvic transaminase) levels in animals caused by hepatotoxic chemical agents Pao, T.T.;Liu, K.T.;Hsu, K.F.;Ung, C.Y.
  79. Acta. Pharm. Sin v.22 Protection by Fructus schizandrea against acetaminophen hepatotoxicity in mice Liu, G.T.;Wei, H.L.
  80. Yakugaku Zasshi v.101 Phamacologycal studies on Schizandra fruit. I, General pharmacological effects of gomisin A and schisandrin Maeda, S.;Sudo, K.;Aburada, M.;Ikeya, Y.;Taguchi, H.;Yosioka, I.;Harada, M.
  81. Biochem. Biophys. Res. Commun. v.186 An immunomodulatory protein, Ling Zhi-8 facilitates cellular interaction through modulation of adhesion molecules Miyasaka, N.;Inoue, H.(et al.)
  82. J. Biol. Chem. v.264 Isolation and characterization of a new immunomodulatory protein, ling zhi-8 (LZ-8), from Ganoderma lucidium Kino, K.;Yamashita, A.(et al.)
  83. Mol. Cells. v.7 no.1 Suppressive effects of Ganoderma lucidum on proliferation of peripheral blood mononuclear cells Kim, R.S.;Kim, H.W.(et al.)
  84. Cell Immunol v.150 Ling Zhi-8: a novel T cell mitogen induces cytokine production and upregulation of ICAM-1 expression Haak-Frendscho, M.;Kino, K.(et al.)
  85. Anticancer Res v.12 The effect of Ganoderma lucidum on induction of differentiation in leukemic U937 cells Lieu, C.W.;Lee, S.S.(et al.)
  86. Int. J. Cancer. v.70 no.6 The anti-tumor effect of Ganoderma lucidum is mediated by cytokines released from activated macrophages and T lymphocytes Wang, S.Y.;Hsu, M.L.(et al.)
  87. Planta Med. v.51 Isolation and hypoglycemic activity of ganoderans A and B, glycans of Ganoderma lucidum fruit bodies Hikino, H.;Konno, C.(et al.)
  88. Planta Med v.56 Mechanisms of hypoglycemic activity of ganoderan B: a glycan of Ganoderma lucidum fruit bodies Hikino, H.;Ishiyama, M.(et al.)
  89. Planta Med v.55 Hypoglycemic actions of some heteroglycans of Ganoderma lucidum fruit bodies Hikino, H.;Mizuno, T.
  90. Chem. Pharm. Bull. v.33 no.3 The biologically active constituents of Ganoderma lucidum (Fr.) Karst. Histamine release-inhibitory triterpenes Kohda, H.;Tokumoto, W.(et al.)
  91. Agents Actions v.23 no.3-4 Anti-allergic constituents in the culture medium of Ganoderma lucidum.(II). The inhibitory effect of cyclooctasulfur on histamine release Tasaka, K.;Mio, M.(et al.)
  92. J. Nutr. Sci. Bitaminol. v.24 Dietary effect of Ganoderma lucidum mushroom on blood pressure and lipid levels in spontaneously hypertensive rats Kabir, Y.;Kimura, S.(et al.)
  93. Am. J. Chin. Med. v.21 Evaluation of the anti-inflammatory and liver-protective effects of anoectochilus formosanus, ganoderma lucidum and gynostemma pentaphyllum in rats Lin, J.M.;Lin, C.C.(et al.)
  94. J. Ethnopharmacol v.47 Radical scavenger and antihepatotoxic activity of Ganoderma formosanum, Ganoderma lucidum and Ganoderma neo-japonicum Lin, J.M.;Lin, C.C.(et al.)
  95. 현대한방강좌 박성수;염태환
  96. Shoyskugaku Zasshi v.17 Pharmacological studies on crude drugs VIII, A consideration on diuretic crude drugs Haginiwa, J.;Harata, M.
  97. Jap. J. Pharmac. v.20 Hypocholesterolemic effect of alisol A-24-monoacetate and its related compounds in rats Imai, Y.;Matsumura, H.;Aramaki, Y.
  98. Chem. Pharm. Bull. v.18 no.7 Biological active triterpenes of Alismatis Rhizoma Murata, T.;Imai, Y.;Hirata, Y.;Miyamoto, M.
  99. Journal of the Pharmaceutical Society of Korea v.19 Crude drugs acting on the renal function. On Atractylis, Hoelen, Alisma and Polyporus Ko, S.T.
  100. Kor. J. Pharmacog. v.12 no.4 Effect of alisols isolated from Alisma orientale Juzep. against several agonists in isolated rat ileum Yun, H.S.;Chung, S.H.;Kim, Y.S.
  101. Shoyakugaku Zasshi v.36 Diuretic principles of Alisma plantago-aquatica var. orientale, Rhizomes Hikino, H.;Iwagawa, T.;Oshima, Y.;Nishikawa, K.;Murata, T.
  102. Yakugaku Zasshi v.104 no.6 Pharmacological analysis of the traditional Chinese prescription Tanaka, S.;Akira, T.;Tabata, M.
  103. Kor. J. Pharmacogn. v.17 no.4 Studies on the efficacy of combined preparation of Crude Drugs(X X XI) Nam, S.K.(et al.)
  104. Phytochemistry v.27 no.4 Triterpenoids from the rhizomes of Alisma plantago-aquatica Geng, P.W.(et al.)
  105. Chem. Pharm. Bull v.40 no.9 Orientalos A, B and C sesquiterpeneconstituents from Chinese Alismatis Rhizoma and revised structures of alismol and alismoxide Yoshikawa, M.(et al.)
  106. Tetrahedron letters v.1 New triterpenes of Alisma plantago - aquatica L. var orientale Samuels Murata, T.;Shinohara, M.;Hirata, T.;Kamiya, K.;Nishikawa, M.;Miyamoto, M.
  107. 효성여대 대학원 약학석사 학위 논문 택사추출액이 benzopyrene에 의해 유도된 간장해에 미치는 영향 서민지
  108. 원광대학교 대학원 약학석사 학위논문 차전자 수침 엑스의 간보호 및 항섬유화에 관한 연구 이미현
  109. J. Pathol v.35 Ligation of the common bile duct Cameron, G.R.;Oakley, C.L.
  110. Br. J. Exp. Pathol v.65 Prolonged bile duct obstruction: a new experimental model for cirrhosis in the rat Kountras, J.;Billing, B.H.;Scheuer, P.J.
  111. Am. J. Pathol. v.137 no.6 Reversibility of hepatic gibrosis in experimentally induced cholestasis in rat Abdel-Aziz, G.;Lebeau, G.;Rescan, P.Y.;Clement, B.;Rissel, M.;Deugn, R.Y.;Campion, J.P.
  112. 간계내과학 김병운(외)
  113. J. hepatol. v.5 A morphological study of the early stages of hepatic fibrosis induced by low doses of dimethylnitrosamine in the rat Jezequel, A.M.;Mancini, R.;Rindaldesi, M.L.;Macarri, G.;Venturini, C.;Orland, F.