Effects of Epimedium Koreanum Extract on the Carbon Tetrachloride-Induced Liver Damage and Its Related Organ Damages in Rats

음양곽 추출물이 사염화탄소 투여로 유발된 간손상 및 연관된 장기 손상의 회복에 미치는 영향

  • Kim, In-Su (Department of Veterinary Internal Medicine, College of Veterinary Medicine, Kyungpook National University) ;
  • Kim, Joo-Wan (Department of Veterinary Internal Medicine, College of Veterinary Medicine, Kyungpook National University) ;
  • Kim, Hong-Tae (Busan Metropolitan City Institute of Health and Environment) ;
  • Lee, Sung-Dong (Department of Veterinary Internal Medicine, College of Veterinary Medicine, Kyungpook National University) ;
  • Ku, Sae-Kwang (Laboratory of Anatomy and Histology, College of Oriental Medicine, Daegu Haany University) ;
  • Do, Yoon-Jung (National Institute of Animal Science) ;
  • Lee, Keun-Woo (Department of Veterinary Internal Medicine, College of Veterinary Medicine, Kyungpook National University)
  • Accepted : 2011.06.13
  • Published : 2011.08.30

Abstract

To evaluate hepatoprotective effect of Epimedium Koreanum nakai (EKN) on liver-damaged animal model, rats were intoxicated with carbon tetrachloride (1 ml/kg) for 9 weeks orally. Liver-damaged rats were divided into 2 groups: liver-damaged control (LDC) group and EKN group were administered vehicle (saline), EKN extract per os for 4 weeks respectively. Normal control (NC) group was administered saline as the same process of LDC group. The weights of prostate (absolute), testis (relative), epididymis (relative) and packed cell volume (PCV), mean corpuscular volume (MCV) of EKN group significantly (P < 0.05) increased compared with LDC group. But Mean corpuscular hemoglobin (MCH), mean corpusulcar hemoglobin concentration (MCHC) and aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) were significantly (P < 0.01, P < 0.05) decreased. Fibrotic regions in hepatic parenchyma of EKN group significantly (P < 0.01) decreased compared with LDC group and mean diameters of hepatic lobules significantly (P < 0.01) increased. Percentages of degenerative kidney regions and number of degenerative kidney tubules, number of vasodilated atrophic glomerulus of EKN group was significantly (P < 0.01, P < 0.05) decreased compared with LDC group. Number of atrophic seminiferous tubules and epididymal tubules showing oligospermatozoa of EKN group were significantly (P < 0.01) decreased compared with LDC group. In conclusion, EKN extract has a favorable effect on the $CCl_4$-induced liver damage.

Keywords

References

  1. 강삼식, 김주선, 강륜정, 한혜경. 음양곽성분에 관한 연구(II) 삼지구엽초 지하부의 성분. 한국생약학회지. 1990; 21: 56-59.
  2. 강삼식, 신국현, 정순간, 조의환. 음양곽의 flavonoid 성분에 관한 연구. 한국생약학회지 1988; 19: 93-96.
  3. 김성렬, 김진환, 김승겸. 음양곽 추출물 중의 항산화성분의 분리 및 성질. 한국식품과학회지. 1992; 24: 535-540.
  4. 김태정. 한국의 자원식물. 서울대학교출판사. 1996: 282.
  5. 노준현, 김영진, 김세원, 이진하, 이현용. 국내산과 중국산 삼지구엽초의 생리활성 비교. 한국약용작물학회지. 2003; 11: 195-200.
  6. 이종원, 도재호, 이성계. 음양곽의 항산화활성. 한국식품영양과학회지. 2000; 29: 732-736.
  7. 하배진, 김희진, 이상헌, 하종명, 이상현, 이재화, 이동근, 박은경, 남천석. 음양곽의 항산화작용에 의한 간 보호 효과. 생명과학회지. 2005; 15: 572-577.
  8. 하배진, 남천석, 박은경, 강금석. 음양곽과 함초의 간독성에 대한 연관성. 신라대학교 자연과학연구소 논문집. 2006; 15: 55-60.
  9. Brown RR, Miller JA, Miller EC. The metabolism of methylated aminoazo dyes. IV. Dietary factors enhancing demethylation in vitro. J Biol Chem 1954; 209: 211-222.
  10. Castilla-Cortazar I,Garcia M, Quiroga J, Diez N, Diez- Caballero F, Calvo A, Diaz M, Prieto J. Insulin-like growth factor-I reverts testicular atrophy in rats with advanced cirrhosis. Hepatology 2000; 31: 592-600. https://doi.org/10.1002/hep.510310308
  11. Chatterjee A. Role of ascorbic acid in the prevention of gonadal inhibition by carbon tetrachloride. Endokrinologie 1967; 51: 319-322.
  12. Dogukan A, Akpolat N, Celiker H, Ilhan N, Halil Bahcecioglu I, Gunal AI. Protective effect of interferon-alpha on carbon tetrachloride-induced nephrotoxicity. J Nephrol. 2003; 16: 81-84.
  13. Elida VC, Jose AC. Lipid peroxidation, necrosis and the in vivo depression of liver glucose 6-phosphatase by carbon tetrachloride. Exp Mol Pathol 1971; 14: 43-56. https://doi.org/10.1016/0014-4800(71)90051-7
  14. Fukai T, Nomura T. Seven prenylated flavonol glycosides from two Epimedium species. Phytochemistry 1988; 27: 259-266. https://doi.org/10.1016/0031-9422(88)80627-7
  15. Harvey PJ, Gready JE, Yin Z, Le Couteur DG, McLean AJ. Acute oxygen supplementation restores markers of hepatocyte energy status and hypoxia in cirrhotic rats. J Pharm Exp Ther 2000; 293: 641-645.
  16. Horn MM, Ramos AR, Winkelmann L, Matte US, Goldani HA, Silveira TR. Seminiferous epithelium of rats with food restriction and carbon tetrachloride-induced cirrhosis. Int Braz J Urol 2006; 32: 94-99. https://doi.org/10.1590/S1677-55382006000100016
  17. Jadon A, Bhadauria M, Shukla S. Protective effect of Terminalia belerica Roxb. and gallic acid against carbon tetrachloride induced damage in albino rats. J Ethnopharmacol 2007; 109: 214-218. https://doi.org/10.1016/j.jep.2006.07.033
  18. Kalla NR, Bansal MP. Effect of carbon tetrachloride on gonadal physiology in male rats. Acta Anat (Basel) 1975; 91: 380-385. https://doi.org/10.1159/000144399
  19. Karagiannis A, Harsoulis F. Gonadal dysfunction in systemic diseases. Eur J Endocrinol 2005; 152: 501-513. https://doi.org/10.1530/eje.1.01886
  20. Lee WY, Lee SD, Son SI, Chang HS, Kim YH, Oh TH, Eom KD. Chang KH, Park SC, Yamato O, Maede Y, Lee KW. The effect of Artemisia capillaris crude juice extract on $CCl_4$ induced liver damage in dogs. J Vet Clin. 2003; 20: 389-395.
  21. Li WK, Xiao PG, Pan JQ. Complete assignment of $^1H$ and $^{13}C$ NMR spectra of ikarisoside A and epimedoside C. Magn Reson Chem. 1998; 36: 303-304. https://doi.org/10.1002/(SICI)1097-458X(199804)36:4<303::AID-OMR187>3.0.CO;2-I
  22. Lim MK, Kim JW, Kim JE, Kim HT, Jung SJ, Kang MY, Lee KW. The therapeutic effect of Hovenia dulcis Thunberg extracts and 6 type of herbal extracts on $CCl_4-induced$ acute liver and kidney damages in rats. J Vet Clin 2007; 24: 400-405.
  23. Lim MK, Kim JW, Kim HT, Lee BJ, Ku SK, Kang MY, Lee KW. Therapeutic effect of Hovenia dulcis Thunberg extracts and 6 types herbal extracts on $CCl_4-induced$ chronic organ damages in the rats-liver and kidney. J Vet Clin 2007; 24: 384-391.
  24. Liu ZQ, Luo XY, Sun YX, Wu W, Liu CM, Liu ZQ, Liu SY. The antioxidative effect of icariin in human erythrocytes against free-radical-induced haemolysis. J Pharm Pharmacol 2004; 56: 1557-1562. https://doi.org/10.1211/0022357044869
  25. Martinez-Mier G, Toledo-Pereyra LH, McDuffie JE, Warner RL, Hsiao C, Stapleton SR, Ward PA. Exogenous nitric oxide downregulated MIP-2 and MIP-1alpha chemokines and MAPK p44/42 after ischemia and reperfusion of the rat kidney. J Invest Surg 2002; 15: 287-296. https://doi.org/10.1080/08941930290086083
  26. Ozturk F, Ucar M, Ozturk IC, Vardi N, Batcioglu K. Carbon tetrachloride-induced nephrotoxicity and protective effect of betaine Sprague-Dawley rats. Urology 2003; 62: 353-356. https://doi.org/10.1016/S0090-4295(03)00255-3
  27. Park EJ. Jeon CH, Ko G, Kim J. Sohn DH. Protective effect of curcumin in rat liver injury induced by carbon tetrachloride. J Pharm Pharmacol 2000; 52: 437-440. https://doi.org/10.1211/0022357001774048
  28. Raymond P. Plaa GL. Effect of dosing vehicle on the hepatotoxicy of CCl4 and nephrotoxicity of CHCl3 in rats. J Toxicol Environ Health. 1997; 51: 463-473.
  29. Recknagel RO, Glende EA Jr, Dolak JA, Waller RL. Mechanisms of carbon tetrachloride toxicity. Pharmacol Ther 1989; 43: 139-154. https://doi.org/10.1016/0163-7258(89)90050-8
  30. Reitman S, Frankel S. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol. 1957; 28: 56-63.
  31. Robbins BH. The absorption, distribution and excretion of carbon tetrachloride in dogs under various conditions. J Pharmacol Exp Ther. 1929; 37: 203-216.
  32. Shukla S, Bhadauria M, Jadon A. Effect of propolis extract on acute carbon tetrachloride induced hepatoxicity. Indian J Exp Biol 2004; 42: 993-997.
  33. Schulze RM, Kappus H. Lysis of erythrocytes as a result of microsomal lipid peroxidation induced by CCl4 or FeCl2. Res Commun Chem Pathol Pharmacol 1980; 27: 129-137.
  34. Sipes IG, McQueen CA, Gandolfi AJ. Hepatic and gastrointestinal toxicology vol 9. In: Comprehensive toxicology. New York: Pergamon. 1997: 251-271.
  35. Song KH, Kim DH, Choi KJ. The effect of aqua-acupuncture of total saponin on the damaged liver induced by carbon tetrachloride in rats. Korean J Vet Clin Med 1996; 13: 108-113.
  36. Sun PY, Ye W, Zhao JF, Pei Y, Wang ZX, Chen YJ, Ogihara Y, Takeda T. Studies on the constituents of Epimedium koreanum. Chem Pharm Bull 1995; 43: 703-704. https://doi.org/10.1248/cpb.43.703
  37. Valcheva-Kuzmanova S, Borisova P, Galunska B, Krasnaliev I, Belcheva A. Hepatoprotective effect of the natural fruit from Aronia Melanocarpa on carbon tetrachloride-induced acute liver damage in rats. Exp Toxicol Pathol 2004; 56: 195-201. https://doi.org/10.1016/j.etp.2004.04.012
  38. Valcheva-Kuzmanova SV. Popova PB, Krasnaliev IJ, Galunska BT, Belcheva W. Protective effect of BP 2-94, a histamine H3- receptor agonist prodrug, in an model of carbon tetrachlorideinduced hepatoxicity in rats. Folia Med (Plovdiv). 2004; 46: 36-41.
  39. Yamauchi M, Takeda K, Sakamoto K, Searashi Y, Uetake S, Kenichi And H, Toda G. Association of polymorphism in the alcohol dehydrogenase 2 gene with alcohol-induced testicular atrophy. Alcohol Clin Exp Res 2001; 25: 16S-18S. https://doi.org/10.1111/j.1530-0277.2001.tb02411.x
  40. Yao HW, Li J, Chen JQ, Xu SY. Inhibitory effect of leflunomide on hepatic fibrosis induced by CCl4 in rats. Acta Pharmacol Sin 2004; 25: 915-920.
  41. Zhang ZB, Yang QT. The testosterone mimetic properties of icariin. Asian J Androl 2006; 8: 601-605. https://doi.org/10.1111/j.1745-7262.2006.00197.x