DOI QR코드

DOI QR Code

Screening of Anti-thrombotic Activity of Herbal Extracts in Ferric Chloride-induced Thrombosis Model

경동맥 혈전 유발 동물모델을 이용한 한약재 추출물의 효능 검색

  • Park, In Sil (KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine) ;
  • Lee, Ki Mo (KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine) ;
  • Lee, In Sun (KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine) ;
  • Han, Jae Il (Laboratory Medicine Team, ASAN Medical Center) ;
  • Jeon, Won Kyung (KM-Based Herbal Drug Development Group, Korea Institute of Oriental Medicine)
  • 박인실 (한국한의학연구원 한의신약개발그룹) ;
  • 이기모 (한국한의학연구원 한의신약개발그룹) ;
  • 이인선 (한국한의학연구원 한의신약개발그룹) ;
  • 한재일 (현대아산병원) ;
  • 전원경 (한국한의학연구원 한의신약개발그룹)
  • Received : 2013.08.22
  • Accepted : 2013.09.22
  • Published : 2013.09.30

Abstract

Objectives : The aim of this study was to examine anti-thrombotic effect of traditional herbal extracts in a rat model of ferric chloride ($FeCl_3$)-induced carotid arterial thrombosis. Methods : Thirty minutes prior to a 35% $FeCl_3$ application, Sprague Dawley(SD) rats were injected with the 10 types of traditional herbal extracts (100mg/kg, intraperitoneal injection), respectively. The effect of these herbal extracts was examined for time to occlusion(TTO) using the Laser doppler flow meter and measured for thrombus weight (TW) in $FeCl_3$-induced thrombosis model. Results : In the TTO, Salvia miltiorrhiza (Sm, $2.30{\pm}0.28$ min, p<0.001) and Santalum album (Sa, $2.19{\pm}0.19$ min, p<0.001) showed significantly delayed TTO more than twice compared with Saline-treated group. Cnidium officinale (Co), Psoralea corylifolia (Pc), Scutellatia baicalensis (Sba), Panax notoginseng (Pn), Angelica tenuissima (At), Scrophularia buergeriana (Sbu), Rhus verniciflua (Rv) and Picrasma quassioides (Pq), except for Rhus verniciflua (Rv) also meaningfully impeded TTO more than one fold. In addition, Salvia miltiorrhiza, Santalum album, Cnidium officinale, Psoralea corylifolia and Scutellatia baicalensis significantly reduced TW more than 10% compared with Saline-treated group. Especially, Salvia miltiorrhiza and Santalum album showed the most excellent anti-thrombotic effect among the 10 herbal extracts tested on the restoration of altered TTO and TW. Conclusions : These results suggest that Sm and Sa extracts have outstanding anti-thrombotic effect in $FeCl_3$-induced thrombosis model and is potentially useful as herbal medicines for the treatment and prevention of thrombosis.

Keywords

References

  1. Xiang YZ, Kang LY, Gao XM, Shang HC, Zhang JH, Zhang BL. Strategies for antiplatelet targets and agents. Thrombo Res. 2008 ; 123 : 35-49. https://doi.org/10.1016/j.thromres.2008.05.003
  2. Ross R. Atherosclerosis-an inflammatory disease. N Engl Med. 1999 ; 340 : 115-26. https://doi.org/10.1056/NEJM199901143400207
  3. Huh Jun, Dongyibogam. Seoul : Namsangdang. 1980 : 134-5.
  4. Lee JO, Kim CY, Lee SW, Oak MH. Antiplatelet and antithrombotic activities of Lindera obtusiloba extract in vitro and in vivo. J Appl Pharmacology. 2010 ; 18(2) : 205-10. https://doi.org/10.4062/biomolther.2010.18.2.205
  5. Nutescu EA, Shapiro NL, Ibrahim S, West P. Warfarin and its interactions with foods, herbs and other dietary supplements. Expert Opin Drug Saf. 2006 ; 5(3) : 433-51. https://doi.org/10.1517/14740338.5.3.433
  6. Miwa K, Kambara H, Kawai C. Effect of aspirin in large doses on attacks of variant angina. Am Heart J. 1983 ; 105 : 351-5. https://doi.org/10.1016/0002-8703(83)90548-3
  7. Verstraeta M, Lijnen HR, Collen D. Thrombolytic agents in development. Drugs. 1995 ; 50 : 29-42. https://doi.org/10.2165/00003495-199550010-00003
  8. Lee IS, Choi SG, Jeon WK. Optimization of ferric chloride induced carotid artery thrombosis model in a rat : Effect of Ginkgo biloba extracts. Kor J Clinical Laboratory Sciences. 2011 ; 43(4) : 179-87.
  9. Day SM, Reeve JL, Pedersen B, Ferris DM, Myers DD, Im M, Wakefield TW, Mackman N, Fay WP. Microvascular thrombosis is driven by tissue factor derived primarily from the blood vessel wall. Blood. 2005 ; 105 : 192-8. https://doi.org/10.1182/blood-2004-06-2225
  10. Prandoni P, Bilora F, Marchiori A, Bernardi E, Petrobelli F, Lensing AW, Prins MH, Girolami A. An association between atherosclerosis and venous thrombosis. N Engl J Med. 2003 ; 348 : 1435-41. https://doi.org/10.1056/NEJMoa022157
  11. van Zanten GH, de Graaf S, Slootweg PJ, Heijnen HF, Connolly TM, de Groot PG, Sixma JJ. Increased platelet deposition on atherosclerotic coronary arteries. J Clin Invest. 1994 ; 93 : 615-32. https://doi.org/10.1172/JCI117014
  12. Bang YJ. Practical Chinese Internal Medicine. Shanghai : Shanghai Science Technology . 1988 : 439-49.
  13. Boos CJ, Lip GY. Blood clotting. inflammation, and thrombosis in cardiovascular events : perspectives. Frontiers in Bioscience. 2006 ; 11 : 328-36. https://doi.org/10.2741/1800
  14. Guemsungsa. Pathology of Eastern Medicine. DaeJeon : Hanlimone. 1994 : 348-56.
  15. Kim SK, Jeon WK. Effects of modified Je-Ho-Tang on ferric chloride-induced thrombosis in a rat model and of peripheral circulatory disturbance in a mouse model. J Korean Soc Appl Biol Chem. 2010 ; 53 : 842-6. https://doi.org/10.3839/jksabc.2010.128
  16. Jeon WK, Yoo BK, Kim YE, Park SO, Park SM, Ko BS. Effect of extracts for herbal medicines on the inhibition of whole blood aggregation. J Korean Soc Appl Biol Chem. 2007 ; 50(4) : 352-7.
  17. Heo EJ, Lee IS, Kang HW, Jeon WK. Effectos of Sokmyong-tang on ferric chloride-induced carotid injury and thrombosis in a rat model. Korean J Orient Physiol Pathol. 2012 ; 26(5) : 732-7.
  18. Eckly A, Hechler B, Freund M, Zerr M, Cazenave JP, Lanza F, Mangin PH, Gachet C. Mechanisms underlying FeCl3-induced arterial thrombosis. J Thrombo Haemost. 2011 ; 9 : 779-89. https://doi.org/10.1111/j.1538-7836.2011.04218.x
  19. Osterud B. The role of platelets in decrypting monocyte tissue factor. Semin Hematol. 2001 ; 38(4 Suppl 12) : 2-5. https://doi.org/10.1053/shem.2001.28832
  20. Yu WG, Xu LN. Effect of acetylsalvianolic acid A on platelet function. Yao Xue Xue Bao. 1994 ; 29(6) : 412-6.
  21. Zou ZW, Xu LN, Tian JY. Antithrombotic and antiplatelet effects of rosmarinic acid, a water-soluble component isolated from radix Salviae miltiorrhizae (danshen). Yao Xue Xue Bao. 1993 ; 28(4) : 241-5.
  22. Yang SA, Im NK, Lee IS. Effect of methanolic extract from Salvia miltiorrhiza Bunge on in vitro antithrombotic and antioxidative activities. Korean J Food Sci Technol. 2007 ; 39(1) : 83-7.
  23. Fan HY, Fu FH, Yang MY, Xu H, Zhang AH, Liu K. Antiplatelet and antithrombotic activities of salvianolic acid A. Thromb Res. 2010 ; 126(1) : 17-22. https://doi.org/10.1016/j.thromres.2010.04.006
  24. Liu J, Zhang D, Li J, Feng J, Yang X, Shi D, Liang X. Effects of Salvia miltiorrhiza and Carthamus tinctorius aqueous extracts and compatibility on rat myocardial ischemic reperfusion injury. Zhongguo Zhong Yao Za Zhi. 2011 ; 36(2) : 189-94.
  25. Dong JC, Xu LN. Beneficial effects of acetylsalvianolic acid A on focal cerebral ischemic rats subjected to middle cerebral artery thrombosis. Yao Xue Xue Bao. 1996 ; 31(1) : 6-9.
  26. Sung YW, Lee JH, Koo BS, Kim GW. Preventive effects of Santalum album L. extracts on oxidation, platelet aggregation and thrombosis. J Orient Neuropsychiatry. 2012 ; 23(1) : 115-29. https://doi.org/10.7231/JON.2012.23.1.115
  27. Tzeng SH, Ko WC, Ko FN, Teng CM. Inhibition of platelet aggregation by some flavonids. Thromb Res. 1987 ; 45 : 477-84. https://doi.org/10.1016/0049-3848(87)90310-0
  28. Ramalingam M, Park YK. Free radical scavenging activities of Cnidium officinale Makino and Ligusticum chuanxiong Hort. methanolic extracts. Pharmacogn Mag. 2010 ; 6(24) : 323-30. https://doi.org/10.4103/0973-1296.71794
  29. Tang SY, Gruber J, Wong KP, Halliwell B. Psoralea corylifolia L. inhibits mitochondrial complex I and proteasome Activities in SH-SY5Y Cells. Ann N Y Acad Sci. 2007 ; 1100 : 486-96. https://doi.org/10.1196/annals.1395.053
  30. Zhang XW, Li WF, Li WW, Ren KH, Fan CM, Chen YY, Shen YL. Protective effects of the aqueous extract of Scutellaria baicalensis against acrolein-induced oxidative stress in cultured human umbilical vein endothelial cells. Pharm Biol. 2011 ; 49(3) : 256-61. https://doi.org/10.3109/13880209.2010.501803
  31. Kim JG, Park SD, Park WH. Influence of Panax notoginseng on the atherosclerosis induced by high-cholesterol feed in Rats. Korean J Orient Physiol Pathol. 2006 ; 20(5) : 1187-95.
  32. Ka MH, Choi EH, Chun HS, Lee KG. Antioxidative activity of volatile extracts isolated from Angelica tenuissimae roots, peppermint leaves, pine needles, and sweet flag leaves. J Agric Food Chem. 2005 ; 53(10) : 4124-9. https://doi.org/10.1021/jf047932x
  33. Jeong EJ, Ma CJ, Lee KY, Kim SH, Sung SH, Kim YC. KD-501, a standardized extract of Scrophularia buergeriana has both cognitive-enhancing and antioxidant activities in mice given scopolamine. J Ethnopharmacol. 2009 ; 121(1) : 98-105. https://doi.org/10.1016/j.jep.2008.10.006
  34. Jung YT, Lee IS, Whang K, Yu MH. Antioxidant effects of Picrasma quassioides and Chamaecyparis obtusa (S. et Z.) ENDL extracts. J Life Sci. 2012 ; 22(3) : 354-9. https://doi.org/10.5352/JLS.2012.22.3.354
  35. Jeon WK, Lee JH, Kim HK, Lee AY, Lee SO, Kim YS, Ryu SY, Kim SY, Lee YJ, Ko BS. Anti-platelet effects of bioactive compounds isolated from the bark of Rhus verniciflua Stokes. J Ethnopharmacol. 2006 ; 106 : 62-9. https://doi.org/10.1016/j.jep.2005.12.015
  36. Yao SK, Ober JC, McNatt J, Benedict CR, Rosolowsky M, Anderson HV, Cui K, Maffrand JP, Campbell WB, Buja LM. ADP plays an important role in mediating platelet aggregation and cyclic flow variations in vivo in stenosed and endothelium-injured canine coronary arteries. Circ Res. 1992 ; 70 : 39-48. https://doi.org/10.1161/01.RES.70.1.39