지구자나무 추출물이 사염화탄소로 유발된 흰쥐의 간손상에 미치는 영향

Protective Effects of Extracts of Hovenia dulcis Thunb on Hepatotoxicity in Carbon Tetrachloride Intoxicated Rats

  • 발행 : 2001.12.01

초록

지구자나무 methanol 추출물의 hexane, chloroform, ethylacetate, butanol 및 $H_2O$ 분획물이 $CCl_4$로 급성 간 독성이 유발된 흰쥐의 효소 활성과 항산화 활성 효과를 검토한 결과, 대조군과 비교하여 $CCl_4$ 단독 투여군에서 ALT, AST, ALP, ${\gamma}$-GTP 및 LDH의 활성과 bilirubin, cholesterol 및 TG의 함량이 유의적으로 증가(p<0.05)하였으나, ALT및 AST 활성도는 $CCl_4$ 단독 투여군과 비교하여 chloroform 분획물을 투여한 군에서, ALP 활성도는 hexane 분획물을 투여한 군에서, bilirubin 함량은 butanol과 $H_2O$ 분획물을 각각 투여한 군에서, cholesterol 함량은 chloroform 과 $H_2O$ 분획물을 각각 투여한 군에서, TG 함량은 chloroform 분획물을 투여한 군에서 유의적인 감소(p<0.05)를 나타내었다. 또한 간조직 중 의 과산화 지질함량과 SOD, catalase및 GSH-PB(활성은 대조군과 비교하여 $CCl_4$ 단독 투여군에서 유의적인 증가(p<0.05)를 나타내었으나, 과산화 지질 함량은 $CCl_4$ 단독 투여군과 비교하여 hexane, chloroform, butanol 및 $H_2O$ 분획물을 각각 투여한 군에서, catalase 활성은 chloroform, ethylacetate, butanol 및 $H_2O$를 각각 투여한 군에서, GSH-Px 활성은 chloroform, butanol 및 $H_2O$ 분획물을 각각 투여한 군에서 유의적인 감소(p<0.05)를 나타내었다. 한편, Blutathione함량과 GST 활성은 대조군에 비해 $CCl_4$ 단독 투여군에서 유의적인 감소 (p<0.05)를 나타내었으나, glutathione 함량은 chloroform과 ethylacetate를 각각 투여한 군에서, GST 활성은 hexane과 chloroform을 각각 투여한 군에서 $CCl_4$단독 투여군과 비교하여 유의적인 증가(p<0.05)를 나타내었다. 따라서 본 실험 결과 지구자나무 분획물이 $CCl_4$로 유발된 흰쥐의 간 손상에 미치는 영향을 검토한 결과, chlornform 분획물이 간세포의 괴사와 변성에 지표가 되는 ALT와 AST 활성도의 저하효과와 간 손상에 따른 과산화 지질 함량과 SOD, Catalase, GSH-Px등의 활성 감소, glutathione함량 및 GST활성의 증가를 나타내어 생채내의 free radical에 의한 간보호 작용이 있는 생리활성 물질을 함유하고 있음이 추정되며, 아울러 이 분획물을 더욱 분리하여 물질의 구조와 반응 기전 제시와 함께 간 손상의 예방 및 치료에 도움이 될 수 있는 물질을 개발할 가치가 있다고 사료된다

This study was performed to investigate the protective effects of Hovenia dulcis Thunb on hepatotoxicity in carbon tetrachloride-intoxicated rats. Male Sprague-Dawley rats (220~240 g) were used as experimental groups, which were divided into 7 groups; Control group, $CCl_4$-treated group, hexane fraction pretreated and $CCl_4$-treated group, chloroform fraction pretreated and $CCl_4$-treated group, ethylacetate fraction pretreated and $CCl_4$-treated group, butanol fraction pretreated and $CCl_4$-treated group, $H_2O$ fraction pretreated and $CCl_4$-treated group. After 6 days, the activities of aminotransferase, contents of cholesterol, TG and hepatic lipid peroxide content in chloroform fraction pretreated and $CCl_4$-treated group were significantly decreased (p<0.05) compared to the only $CCl_4$-treated group. The content of glutathione and activities of GST in chloroform fraction pretreated and $CCl_4$-treated group were also significantly increased (p<0.05) compared to the only $CCl_4$-treated group. In addition, activities of SOD, catalase and GSH-Px in chloroform fraction pretreated and $CCl_4$-treated group were significantly decreased (p<0.05) compared to the only $CCl_4$-treated group. These results indicated that the chloroform fraction of Hovenia dulcis Thunb methanol extract showed hepatoprotective effect in carbon tetrachloride-intoxicated rats.

키워드

참고문헌

  1. Biochem. J. v.293 Radical induced chain oxidation of proteins and its inhibition by chain breaking antioxidants Neuail. J.;Gebick. J.;Stocker. R.
  2. N. Engl. J. Med. v.320 Beyond cholesterol. Modifications of lowdensity lipoproteins that increase its atherogenicity Steinberg. D.;Pathasarathly. S.;Carew. T.E.;Khoo. J.C.;Witztum. J.L.
  3. Biology and Medicine. v.19 The role of oxidative stress in HIV disease. free radical Gary. W.P.;Cynthia. D.L.
  4. Food Technology. v.46 Cancer-preventive foods and ingredients Caragy. A.B.
  5. Biochem. Biophy. Res. Com. v.212 Gingo bibba extract (EGb 761) protects human low density lipoproteins against oxidative modification mediated by copper Liang. J.Y.;Marie. T.;Lester. P.
  6. Korean J. Food Sci. Technol. v.27 antioxidative activity and physiological activity of some Korean medicinal plants Kim. H.K.;Kim. Y.E.;Do. J.R.;Lee. Y.C.;Lee. B.Y.
  7. Int. J. Pharmacognosy. v.34 Biological properties of plant flavonoids: An Overview Middleton. E.
  8. Pharmacol. Rev. v.19 Carbon tetrachloride hepatotoxicity Recknagel. R.O.
  9. Pharmacological Basis of Therapeutics v.7 Carbon tetrachloride Gilman. A.G.
  10. Fund. appl. Toxicology. v.6 Oraltoxicity of carbon tetrachloride : Acute, subacute and subchronic studies in rats Bruckner. J.V.;Mackenzie. W.F.;Muralidhara. S.
  11. Biol. Med. v.5 Free radical Hassan. H.M.
  12. Ann. Rev. Nutr. v.12 Dietary carotenes, vitamin C and vitamin E as protective antioxidants in human cancers Byers. T.;Perry. G.
  13. J. Korean Soc. Food Nutr. v.19 Effects of onion andginger on the lipid peroxidation and fatty acid composition of mackerel during frozen storage Lee. Y.K.;Lee. H.S.
  14. Jungyakdesajon
  15. Korean Resources Plants Kim. T.J.
  16. Biol. Pharm. Bull. v.20 Hepatoprotective effect of Hovenia dulcis THUNB on experimental liver injuries induced by carbon tetrachloride or D-galactosamine/lipopolysaccharide Hase. K.;Ohsugi. M.;Xiong. Q.;Basnet. P.;Kadota. S.;Namba. T.
  17. Chem. Pharm. Bull. v.44 Bioactive saponins and glycosides IV. Absolute stereo structures and inhibitiry activity on histamine release of hovenidulciosides A₁A₂B₁ and B₂ Yoshikawa. M.;Murakami. T.;Ueda. T.;Matsuda. H.;Yamahara. J.;Murakami. N.
  18. Korean J. Food Sci. Technol. v.32 Isolation and identification of 3-methoxy-4-hydroxybenzoic acid and 3-me-thoxy-4-hydroxycinnamic acid from hat water extracts of Hovenia dulcis Thumb and confirmation of their antioxidative and antimicrobial activity Cho. J.Y.;Moon. J.H.;Park. K.H.
  19. Yakugaku Zasshi. v.117 Bioactive constitutents of Chinese natural medicines. III. Absolute stereo structures of new dihydroflavonoids. Hovenitins I. II and III, isolated from hovenia dulcis THUNB: Inhibitory effect on alcohol-induced muscular relaxation and hepatoprotective activity Yoshikawa. M.;Murakami. T.;Ueda. T.;Yoshizumi. S.;Ninomiya. K.
  20. Chem Pharm. Bull. v.41 Antisweet natural products. VIII. Structures of hodulosides VI-X from Hoventia dulcis Thunb var tamentella Makino Yoshikawa. M.;Nagai. Y.;Yoshida. M.;Arihara. S.
  21. Toxicol. Pathol. v.19 Colchicine antimiosis abolishes CCI₄ autoprotection. Rao. V.C.;Nehendale. H.M.
  22. Am. J. Clin. Pathol. v.28 A colorimetric method for the determination of serum glutamic oxaloacetic and glutamic pyruvic transaminase Reitman. S.;Frankel. S.
  23. Sangyo Igaku v.24 Investigation on physiological values of blood in industrial workers, Report 3. Serum colloid reaction and enzyme activity values Kawano. S.;Nakagawa. H.;Toga. H.
  24. Chin. Chem. v.16 A kinetic photometric method for serum γ-glutamyltrans peptidase Szaz. G.
  25. Clin. Chem. v.18 Effect of hydrogen ion concentration on lactate dehydrogenase (LDH) assays King. J.
  26. Clinical chemistry v.26 Mechanism of unterference by hemoglobin in the determination of total bilirubin., 1. Method of Malloy-Evelyn Bruce. C.;Shull. H.L.;Philip. K.L.
  27. J. Lipid Res. v.32 A microenzymatic method to measure cholesterol and triglyceride in lipoprotein subfractions separated by density gradient ultracentrifugation from 2000 microliters of plasma or serum Belcher. J.D.;Egan. J.O.
  28. Anal. Biochem. v.86 Determination of malondialdehyde precursor in tissues by thiobarbituric acid test Uchiyama. M.;Mihara. M.
  29. Arch Biochem Biophy v.82 Tissue sulfhydryl groups Ellman. G.L.
  30. Methods in Enzymatic Analysis v.105 Assay of glutathione peroxidase Flohe. L.;Wolfgng. A.;Gunzler. W.A.
  31. Anal. Biochem. v.249 Glutathione S-transferase, The first enzymatic step in mercapturic avid reaction Habig. W.H.;Pabst. M.J.;Jakoby. W.B.
  32. Methods in Enzymology v.52 Preparation and assay of superoxide dismutase Cropo. C.H.;McCord. J.M.;Fridovich. E.;Fleischer. S.(ed.);Packer. L.(ed.)
  33. Methods of Enzymatic Analysis v.2 Catalase Aebi. H.;Vergmeyer. H.U.(ed.)
  34. J. Biol. Chem. v.193 Protein measurement with folin phenol reagent Lowry. O.H.;Rosebrough. N.;Farr. A.L.;Randall. R.J.
  35. Biometrics v.13 Multiple range test for correlated and heteroscedastic means Duncan. D.B.
  36. Principles and methods of toxicology Hayes;Gabriel. L.P.(ed.);William. R.H.(ed.)
  37. Disease of liver and biliary system (8th ed) Sherlock. D.S.
  38. Gut. v.13 Serum γ-glutamyl transpeptidase activity inliver disease. Whitfield. J.B.;Pounder. R.E.;Neale. G.;Moss. D.W.
  39. Yakhak Hoeji v.43 Protective effects of extracts of Mori Cortec Radicis on carbon tetrachloride induced hepatotocixicity Kim. S.Y.;Lee. H.S.;Ryu. K.S.;Lee. E.J.;Kim. Y.C.
  40. Arch. Biochem. Biophy. v.235 Lipid peroxidation increased the molecular order of microsomal membranes Curtis. M.T.;Glifor. D.;Farber. J.L.
  41. Folia Pharmacol. Japon v.85 Pharmacological studies on schizandra fruits. III. Effects of wuweizisu C, a ligan component of schixanda fruits, on experimental liver injuries in rats Takeda. S.;Funo. s.;IIzuka. A.;Kase. Y.;Arai. I.;Ohkura. Y.;Sudo. K.;Kiuchi. N.;Yoshida. C.;Maeda. S.;Abrada. M.;Hosoya. E.
  42. Biochim. Biophys. Acta v.795 The critical steady state hypoxic conditions in carbon tetrachloride induced lipid peroxidation in rat liver microsomes Noll. T.;Groot. H.
  43. J. Food Hyg. Saftety. v.15 Mechanism and effect of Corydalis ternata on the CCI₄-induced hepatotoxicity Surh. I.O.;Jeong. C.S.;Jung. K.H.
  44. J. Korean Soc. Food. Sci. Nutr. v.30 Inhibitory effect of leek green juice on CCI₄-induced hepatotoxicity in rats Lee. M.Y.
  45. Food, Nutrition and Chemical Toxicity The importance of diet and nutrition in the detoxication of chemicals Parke. D.V.
  46. Ann. Revi. Biochem. v.52 Glutathione Meister. A.;Anderson. M.E.
  47. Chem. Biol. Ineract. v.75 Glutathione s-transferase in relation to their role in the biotransformation of xenobiotics Vos. R.M.;Van. Bladern. P.J.
  48. Determination of glutathione peroxidase. CRC Handbook of Free Radicals and Antioxidations in Biomedicine Floh. L.
  49. Physiol. Rev. v.50 Catalase physical and chemical properties mechanism of catalysis and physiologicalrole Deisseroth. A.;Dounce. A.L.
  50. Arch. Biochem. Biophys. v.210 Metabolism of hydrogen peroxide in isolated hepatocytes relative contributions of catalase and glutathione peroxidase in decomposition of endogenously generated H₂O₂ Jones. D.P.;Eklow. L.;Thor. H.;Orrenius. S.