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Effects of Aqueous Extract of Diospyros Kaki Calyx on Anti-thrombotic Activity in vitro and in vivo

시체(柿蒂)의 in vitro와 in vivo 항혈전 효능 연구

  • Baek, Kyung-Min (Department of Cardiovascular and Neurologic Diseases(Stroke Center), College of Oriental medicine, DaeguHaany University) ;
  • Roh, Seong-Soo (Department of Herbology, College of Oriental medicine, DaeguHaany University)
  • 백경민 (대구한의대학교 한의과대학 심계내과학교실) ;
  • 노성수 (대구한의대학교 한의과대학 본초약리학교실)
  • Received : 2011.11.07
  • Accepted : 2011.12.16
  • Published : 2011.12.30

Abstract

Objectives : The aim of this study is to research an anti-thrombus effect by Diospyros Kaki Calyx. Methods : The healthy human plasma were gained and used in vitro study such as factor X activity (FXa) inhibition, prothrombinase inhibition, prothrombin time (PT) and activated partial thromboplastin time. Fifteen SD rats were divided into three groups ; intact control group (orally administrated with distilled water 5ml/kg) and two experimental group treated with extract of diospyros kaki calyx (EKC). Experimental rats were orally 600 mg/kg concentration of EKC and 200 mg/kg concentration of EKC. After an hour from administration, we anesthetized rats and made arteriovenous (AV) shunt rat models to study weight of thrombus, took whole blood to study content of thromboxane B2 and blood clotting time. Results : In vitro, EKC significantly increased inhibitory activity of FXa, prothrombinase compared with intact control group ($^*P$ <0.05). PT and aPTT were increased in EKC treated (600 mg/kg) group compared with intact control group ($^*P$ <0.05). In vivo, blood clotting time of experiment group treated with EKC 600 mg/kg were significantly increased compare with that of intact control group (p<0.05) and content of thromboxane B2 was significantly decreased in group treated with EKC 600 mg/kg in serum. The weight of thrombus were significantly reduced in group treated with EKC 600 mg/kg compared with intact control group (p<0.05). But in vivo experiment study, those parameters of group treated with EKC 200 mg/kg were relatively decreased compared with those of intact control group without statistical significance. Conclusions : EKC has an antithrombic activity because of inhibition internal course such as FXa and prothrombin. And EKC inhibited a hole blood clotting in vivo experiment by low content of thromboxane B2.

Keywords

References

  1. The Korean education committee of herbal medicine, college of oriental medicine. Seoul : Younglimsa. 2007 : 405-406.
  2. Yan, Yong-He(嚴用和). JiShengFang(濟生方). QuanGuoTuShuGuanWenXianSuoWeiFuZhiZhongXin (全國圖書館文獻縮微復制中心). Beijing. 2004 ; 213-214.
  3. Kim HJ, Park TH, Jung MS and Son JH. Study on the Antioxidant and Antiinflammatory Activities of Sarcocarp and Calyx of Persimmon (Cheongdo Bansi). J. Appl. Biol. Chem. 2011 ; 54(2) : 71-78. https://doi.org/10.3839/jabc.2011.013
  4. Kim SG, Lee YC, Suh KG, and Choi HS. Acetaldehyde dehydrogenase activator from persimmon and its processed foods. J Korean Soc Food Sci Nutr 2001 ; 30 : 954-958.
  5. Harada M, Sakagami R, Watanabe T, Onitsuka T, Katoh H, and Nagai. A Antibacterial and deodorizing effect of persimmon tannin. Jpn J Conserv Dent. 2005 ; 48 : 314-319.
  6. Shinmoto H, Kimura T, Yamagishi K, and Suzuki M. Antimutagenicity of fruit extract on Trp-P2 induced mutagenicity of Salmonella typhimurium TA98. J Jpn Soc Food Sci Tech. 2002 ; 49 : 203-206. https://doi.org/10.3136/nskkk.49.203
  7. Gorinstein S, Bartnikowsaka E, Kulasek G, Zemser M, and Trakhtenberg S. Dietary persimmon improves lipid metabolism in rats fed diets containing cholesterol. J Nutr. 1998 ; 128 : 2023-2027. https://doi.org/10.1093/jn/128.11.2023
  8. Achiwa Y, Hibasami H, Katsuzaki H, Imai K, and Komiya T. Inhibitory effects of persimmon (Diospyros kaki) extract and related polyphenol compounds on growth of human lymphoid leukemia cells. Biosci Biotech Biochem. 1997 ; 61 : 1099-1109. https://doi.org/10.1271/bbb.61.1099
  9. Himbo G, Nadamoto T, Fujisawa F, and Fushiki T. Regulation of the peripheral body temperature by foods : A temperature decrease induced by the Japanese persimmon (kaki, Diospyros kaki). Biosci Biotech Biochem. 2003 ; 67 : 23-28. https://doi.org/10.1271/bbb.67.23
  10. Sa YS, Kim KA and Choi HS. Purification and Characterization of Anti-)) Coagulant Activity Fraction from Persimmon Stem. J. Korean Soc. Food Sci. Nutr. 2003 ; 32(8) : 1323-1327. https://doi.org/10.3746/jkfn.2003.32.8.1323
  11. Wang Ang(汪昂). YiFangJiJie(醫方集解). Seoul : DaXingWenHuaShe(大星文化社). 1992 : 153-154.
  12. Li, Shi-Zhen(李時珍). BenCaoGangMu(本草綱目). Sanghai : ShangHaiKeXueJiShuChuBanShe(上海科學技術出版社). 1993 : 571-572.
  13. Blaha MJ, Bansal S, Rouf R, Golden SH, Blumenthal RS, Defilippis AP. A practical "ABCDE" approach to the metabolic syndrome. Mayo Clin. Proc. 2008 ; 83 : 932-941. https://doi.org/10.1016/S0025-6196(11)60770-2
  14. Collaborative overview of randomized trials of antiplatelet therapy-I : prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration. BMJ. 1994 ; 308 : 81-106. https://doi.org/10.1136/bmj.308.6921.81
  15. CAPRIE Steering Committee. A randomised, blinded trial of clopidogrel versus aspirin in patients at risk of ischemic events(CAPRIE). Lancet. 1996 ; 348 : 1329-1339. https://doi.org/10.1016/S0140-6736(96)09457-3
  16. Thompson PD, Zimet R, Forbes WP, Zhang P. Meta-analysis of results from eight randomized, placebo-controlled trials on the effect of cilostazol on patients with intermittent claudication. Am. J. Cardiol. 2002 ; 90 : 1314-1319. https://doi.org/10.1016/S0002-9149(02)02869-2
  17. Hansen PR, Holm AM, Ki JH, Ledet T, Rasmussen LM, Andersen CB. Pentoxifylline inhibits neointimal formation and stimulates constrictive vascular remodeling after arterial injury. J. Cardiovasc Pharmacol. 1999 ; 34 : 683-689. https://doi.org/10.1097/00005344-199911000-00009
  18. Miwa K, Kambara H, Kawai C. Effect of aspirin in large doses on attacks of variant angina. Am. Heart J. 1983 ; 105 : 351-355. https://doi.org/10.1016/0002-8703(83)90548-3
  19. Jack Hirsh. Progress review : the relationship between dose of aspirin, side-effects and antithrombotic effectiveness. Stroke. 1985 ; 16 : 1-3. https://doi.org/10.1161/01.STR.16.1.1
  20. Cho EA, Kim SY, Na IH, Kim DC, In MJ and Chae HJ. Antioxidant and anticoagulant activities of water and ethanl extracts of Phyllostachys pubescence leaf produced in Geoje. Journal of Applied Biological Chemistry. 2010 ; 53(3) : 170-173. https://doi.org/10.3839/jabc.2010.030
  21. Park YS, Choi HJ. Production of antithrombotic material extracted from auricularia auricularjudae and the verification of its antithrombotic activity via animal test. Journal of Korean Society of Food Engineering. 2010 ; 14(4) : 359-366.
  22. Seo HC. Optimization of anticoagulant production from Phellinus Linteus Mycelia. Korean Journal of mycology. 2011 ; 39(2) : 117-121. https://doi.org/10.4489/KJM.2010.39.2.117
  23. Jang MJ, Rhee SJ, Cho SH, Woo MH and Choi JH. A study on the antioxidative, anti-inflammatory and anti-thrombogenic effects of Zanthoxylum piperitum DC. extract. J. Korean Soc Food Sci Nutr. 2006 ; 35(1) : 21-27. https://doi.org/10.3746/jkfn.2006.35.1.021
  24. Sohn HY, Kwon JS, Son KH, Kwon GS, Ryu HY and Kum EJ Antithrombin and thrombosis prevention activity of Buckwheat Seed, Fagopyrum esculentum moench. J Korean Food Sci Nutr. 2006 ; 35(2) : 132-138. https://doi.org/10.3746/jkfn.2006.35.2.132
  25. Yang WK, Kim HK, Sung YY, Cheon MS and Yoon TS. Comparative study of extracts from Rhubarb on anti-thrombotic and anti-platelet activity. Journal of Korean ASsociation of Herbology. 2010 ; 25(4) : 1-6.
  26. Ryu HY, Kim YK, Kwon US, Kwon CS, Jin IN and Sohn HY. Thrombin inhibition activity of fructus extract of Cataggus pinnatifida bunge. J Korean Society of Life Science. 2007 ; 17(4) : 535-539.
  27. Song GY, Park BJ and Kim SH. Antithrombotic effect of Galla Rhois. Korean Journal of Pharmacognosy. 2002 ; 33(2) : 120-123.
  28. Kim S. A study on the thrombolytic activities of Anemarrhena extracts. Graduate School of Dongshin University. 2007.
  29. Park YS, Song JK, Yoon CH, Chung KS and Choi HS. Anti-platelet and anti-thrombotic effects of Gastrodia Elata. Korean Journal of Pharmacognosy. 1995 ; 26(4) : 385-389.
  30. Roh SS. The effects of Polygonati Rhizoma Preparata on anti-thrombotic activity. The Journal of Applied Oriental Medicine. 2008 ; 8(1) : 13-21.
  31. Roh SS, Park JH. The effects of Ginseng Radix Preparata extract on anti-thrombotic activity. the Journal of East-West Medicine. 2008 ; 33(2) : 47-61.
  32. Yang SA, Im NK, Lee IS. Effects of methanolic extract from Salvia Miltiorrhiza Bunge on in vitro antithrombotic and antioxidative activities. Korean J. Food Sci. Technol. 2007 ; 39(1) : 83-87.
  33. Lee KS, Song BK, Cho BW. Effects of A Constituent Herbs of Samul-tang on Antithrombosis and Antistress. Korean J. Oriental Obstetrics & Gynecology. 1999 ; 12(2) : 41-74.
  34. Je JM. The Experimental Study on Anti-thrombotic and Anti-inflammatory Effect of NeungaSoJeokTang (NSJT). Graduate School of Daejeon University. 2007.
  35. Oh MT. Eom HS. Effect of Tonggyungsamultang on the Intravascular Coagulation induced by Endotoxin in Rats. Korean J. Oriental Pathology. 1996 ; 11(1) : 77-82.
  36. Kim SJ, Kim J, Kim HJ et al. Effect of Naringin on lipie metabolism and antithrombotic capacity in rat. J. Fd Hyg. Safety. 2008 ; 23(4) : 297-303.
  37. Lee MH, Kim MS, Shin HY, Sohn HY. Evaluation of antimicrobial, antioxidant, and antithrombin activity of domestic fruit and vegetable juice. Korean J. Microbiol. Biotechnol. 2011 ; 39 : 146-152.
  38. Heo Jun. Dongeui Bogam. Seoul : BubIn Publishing. 2007 : 1924.
  39. Uchida S, Ozaki M, Akashi T, Yamashita K, Niwa M and Taniyama K. Effects of (-)-epigallocatechin-3-O-gallate(green tea tannin) on the life span of stroke-prone spontaneously hypertensive rats. Clin. Exp. Pharmacol. Physiol. 1995 ; 22 : 302-323. https://doi.org/10.1111/j.1440-1681.1995.tb02928.x
  40. Kameda K, Takaku T, Okuda H, Kimura Y, Okuda T, Haitian T, Agata I and Arichi S. Inhibitory effects of various flavonoids isolated from leaves of persimmon on angiotensinconverting enzyme activity. J. Natl. Prod. 1987 ; 50 : 680-683. https://doi.org/10.1021/np50052a017
  41. Bei WJ, Peng WL, MA Y and XU AL. Flavonoids from the leaves of Diospyros kaki reduce hydrogen peroxide-induced injury in NG108-15 cells. Neurosci. Lett. 2004 ; 363(3) : 262-265. https://doi.org/10.1016/j.neulet.2004.04.031
  42. Zhong S. Feng S. Napthoquinones and a triterpene from stem of Diospyros kaki var sylvestris. Zhongguo. Yaoke. Xerbao. 1987 ; 18(4) : 279-280.
  43. Jo YH, Park JW, Lee JM, Ahn GH, Park HR and Lee SC, Antioxidant and anticancer activities of methanol extracts prepared from different parts of Janseng Daebong persimmon(Diospyros kaki cv. Hachiya). J Korean Soc Food Sci Nutr. 2010 ; 39 : 500-505. https://doi.org/10.3746/jkfn.2010.39.4.500
  44. Kim HJ, Park TS, Jung MS and Son JH. Study on the anti-oxidant and anti-inflammatory activities of sarcocarp and calyx of persimmon(Cheondo Bansi). J Appl. Biol. Chem. 2011 ; 54(2) : 71-78. https://doi.org/10.3839/jabc.2011.013
  45. Jang IC, Jo EK, Bae MS, Lee HJ, Jeon GI, Park EJ, Yuk HG, Ahn GH and Lee SC. Anioxidant and antigenotoxic activities of different parts of persimmon(Diospyros kaki cv. Fuyu) fruit. Journal of Medicinal Plants Research. 2010 ; 4(2) : 155-160.
  46. Korean society for Pathology. Pathology II. Seoul : Gomun Publishing. 1995 : 112-129, 540-542.
  47. Kim JJ. Physiology. Seoul : Gomun Publishing. 1985 : 59-63.
  48. Fisher M. Antithrombotic and thrombolytic therapy for ischemic stroke. J. Thromb. Thrombolysis. 1999 ; 7 : 165-169. https://doi.org/10.1023/A:1008889605137
  49. E. Perzborn, J. Strassburger A. Wilmen, J. Pohlmann, S. Roehrig, K-H. Schlemmer. and A. Straub. In vitro and in vivo studies of the novel antithrombotic agent BAY 59-7939-an oral, direct Factor Xa inhibitor. J. Thromb Haemost. 2005 ; 3 : 514-521. https://doi.org/10.1111/j.1538-7836.2005.01166.x
  50. Ahn KH. The study on antithrombosis and inflammation according to the broth preparation method of Gamijoukyungtang. Graduate School of Wonkwang University. 2009.
  51. Seung KR. Effect of Car thamus t inctor ius L. S emen on Endotox in- Induced Thrombosi s in Rats. Graduate School Duksung Women's University. 2000.
  52. Lee GN, Kwon OH. Clinical Pathological File. Medical Publishing. 2000 ; 1118.
  53. Nelson DL, Cox MM. Lehninger-Principles of Biochemistry 3rd ed. New York : W.H. Freeman and Company. 2001 : 1253-1254.
  54. Kinsella JE, Frankel E, German B, Kanner J. Possible mechanisms of the protective role of antioxidants in wine and plant foods. Food technology 1993 ; 85-89.
  55. J Lorrain, L Millet, I Lechaire, S Lochot, P Ferrari, C Visconte, M Sainte-Marie, C Lunven, CN Berry, P Schaeffer, JM Herbert and SE O'Connor. Antithrombotic Properties of SSR182289A, a New, Orally Active Thrombin Inhibitor. The Journal of Pharmacology And Experimental Therapeutics. 2002 ; 304(2) : 567-574.
  56. James R Pruitt, Donald J Pinto, Melissa J Estrella, Lori L Bostrom, Robert M Knabb, Pancras C Wong, Matthew R Wright and Ruth R Wexler Isoxazolines and Isoxazoles as Factor Xa Inhibitory. Bioorganic & Medicinal Chemistry Letters. 2000 ; 100 : 685-689.