DOI QR코드

DOI QR Code

Nelumbo nucifera Leaves Inhibit HASMC Proliferation and Migration Activated by TNF-$\alpha$

Human Aortic Smooth Muscle Cell에서 하엽(荷葉)의 항동맥경화 활성 연구

  • Kim, Sun-Mo (Department of Prescriptionology, Collage of Oriental Medicine, Dongguk University) ;
  • Yun, Hyun-Jeong (Cardiovascular Medical Research Center, College of Oriental Medicine, Dongguk University) ;
  • Yi, Hyo-Seung (Cardiovascular Medical Research Center, College of Oriental Medicine, Dongguk University) ;
  • Won, Chan-Wook (Department of Prescriptionology, Collage of Oriental Medicine, Dongguk University) ;
  • Kim, Jai-Eun (Cardiovascular Medical Research Center, College of Oriental Medicine, Dongguk University) ;
  • Park, Sun-Dong (Cardiovascular Medical Research Center, College of Oriental Medicine, Dongguk University)
  • 김선모 (동국대학교 한의과대학 방제학교실) ;
  • 윤현정 (동국대학교 한의과대학 심혈관계질환 천연물개발연구센터) ;
  • 이효승 (동국대학교 한의과대학 심혈관계질환 천연물개발연구센터) ;
  • 원찬욱 (동국대학교 한의과대학 방제학교실) ;
  • 김재은 (동국대학교 한의과대학 심혈관계질환 천연물개발연구센터) ;
  • 박선동 (동국대학교 한의과대학 심혈관계질환 천연물개발연구센터)
  • Published : 2009.12.30

Abstract

Objectives : The proliferation and migration of human aortic smooth muscle cells (HASMC) in response to activation by various stimuli plays a critical role in the initiation and development of atherosclerosis. This study was conducted to examine the effects of Nelumbo nucifera leaves (NNL) on the proliferation and migration of HASMC. Additionally, the mechanisms involved in any observed effects were also evaluated. Methods : Apoptotic cells were measured by staining with FITC-labeled annexin V, followed by flow cytometric analysis. The expression level of apoptosis related proteins was confirmed by western blot. And MMP-9 activity was measured by gelatin zymography and MMP-9 expression was measured by ELISA Results : NNL completely inhibited the proliferation of HASMC via induction of the expression of apoptotic proteins including annexin V, cleaved poly ADP-ribose polymerase (PARP), and caspase-3 and -8. NNL treatment resulted in the release of cytochrome c into cytosol, a loss of mitochondrial membrane potential, a decrease in Bcl-2 and Bcl-xL and an increase in Bax expression. NNL also blocked HASMC migration via suppression of MMP-9. Conclusions : Taken together, these results indicate that NNL has the potential for use as an anti-artherosclerosis agent.

Keywords

References

  1. 김창민 外 完譯. 中藥大辭典. 서울 : 정담. 1997 : 4623-5.
  2. Kim SB, Rho SB, Rhyu DY, Kim DW. Effect of Nelumbo nucifera leaves on hyperlipidemic and atherosclerotic Bio F1B hamster. Kor J Pharmacogn. 2005 ; 36(3) : 229-34.
  3. Shin MK, Han SH. Effects of lotus(Nelumbo nucifera Gertn) leaf powder on lipid concentration in rats fed high fat diet rats. Kor J Food culture. 2006 ; 21(2) : 202-8.
  4. Lin MC, Kao SH, Chung PJ, Chan KC, Yang MY, Wang CJ. Improvement for high fat diet-induced hepatic injuries and oxidative stress by flavonoidenriched extract from Nelumbo nucifera leaf. J Agric Food Chem. 2009 ; 57(13) : 5925-32. https://doi.org/10.1021/jf901058a
  5. Ono Y, Hattori E, Fukaya Y, Imai S, Ohizumi Y. Anti-obesity effect of Nelumbo nucifera leaves extract in mice and rats. J Ethnopharmacol. 2006 ; 106(2) : 238-44. https://doi.org/10.1016/j.jep.2005.12.036
  6. 양웅모, 장문석, 박성규 등. 하엽 및 하엽옥천산이 Streptozotocin으로 유발된 당뇨에 미치는 영향. 동의생리병리학회지. 2006 ; 20(6) : 1497-501.
  7. 이경석, 오창석, 이기영. 연잎추출물의 항균효과. 한국식품영양과학회지. 2006 ; 35(2) : 219-23.
  8. 이경석, 김민규, 이기영. 연잎 에탄올 추출물의 항산화효과. 한국식품영양과학회지. 2006 ; 35(2) : 182-6.
  9. Wu MJ, Wang L, Weng CY, Yen JH. Antioxidant activity of methanol extract of the lotus leaf (Nelumbo nucifera Gertn.). Am J Chin Med. 2003 ; 31(5) : 687-98. https://doi.org/10.1142/S0192415X03001429
  10. 장문석, 김향미, 박성규 등. 연잎, 연꽃 및 연꽃 수술 추출물의 Tyrosinase 활성억제 및 Melanin 생성억제에 의한 미백효과. 대한본초학회지. 2007 ; 22(4) :87-94.
  11. 양웅모, 김향미, 박성규 등. 연잎에탄올추출물이 피부주름에 미치는 영향. 대한한의학방제학회지. 2006 ;14(2) : 67-75.
  12. Oh JH, Choi BJ, Chang MS, Park SK. Nelumbo nucifera semen extract improves memory in rats with scopolamine-induced amnesia through the induction of choline acetyltransferase expression. Neurosci Lett. 2009. 11 ; 461(1) : 41-4. https://doi.org/10.1016/j.neulet.2009.05.045
  13. Yuk CS. Coloured medicinal plants of Korea. Academy Book Co Seoul Korea. 219-30. 1990 ;
  14. Lin HY, Kuo YH, Lin YL, Chiang W. Antioxidative effect and active components from leaves of Lotus (Nelumbo nucifera). J Agric Food Chem. 2009. 12 ; 57(15) : 6623-9. https://doi.org/10.1021/jf900950z
  15. Hyun SK, Jung YJ, Chung HY, Jung HA, Choi JS. Isorhamnetin glycosides with free radical and ONOO-scavenging activities from the stamens of Nelumbo nucifera. Arch Pharm Res. 2006 ; 29(4) : 287-92. https://doi.org/10.1007/BF02968572
  16. Jung HA, Jung YJ, Yoon NY, Jeong da M, Bae HJ, Kim DW, Na DH, Choi JS. Inhibitory effects of Nelumbo nucifera leaves on rat lens aldose reductase, advanced glycation endproducts formation, and oxidative stress. Food Chem Toxicol. 2008 ; 46(12) : 3818-26. https://doi.org/10.1016/j.fct.2008.10.004
  17. Ohkoshi E, Miyazaki H, Shindo K, Watanabe H, Yoshida A, Yajima H. Constituents from the leaves of Nelumbo nucifera stimulate lipolysis in the white adipose tissue of mice. Planta Med. 2007 ; 73(12) : 1255-9. https://doi.org/10.1055/s-2007-990223
  18. Shim SY, Choi JS, Byun DS. Kaempferol isolated from Nelumbo nucifera stamens negatively regulates FcepsilonRI expression in human basophilic KU812F cells. J Microbiol Biotechnol. 2009 ; 19(2) : 155-60. https://doi.org/10.4014/jmb.0804.259
  19. Kashiwada Y, Aoshima A, Ikeshiro Y, Chen YP, Furukawa H, Itoigawa M, Fujioka T, Mihashi K, Cosentino LM, Morris-Natschke SL, Lee KH. Anti-HIV benzylisoquinoline alkaloids and flavonoids from the leaves of Nelumbo nucifera, and structureactivity correlations with related alkaloids. Bioorg Med Chem. 2005 ; 13(2) : 443-8. https://doi.org/10.1016/j.bmc.2004.10.020
  20. Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999. Jan 14 ; 340(2) : 115-26. https://doi.org/10.1056/NEJM199901143400207
  21. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993. Apr 29 ; 362(6423) : 801-9. https://doi.org/10.1038/362801a0
  22. Fischman DL, Leon MB, Baim DS, Schatz RA, Savage MP, Penn I, Detre K, Veltri L, Ricci D, Nobuyoshi M, et al. A randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators. N Engl J Med. 1994. Aug 25 ; 331(8) : 496-501. https://doi.org/10.1056/NEJM199408253310802
  23. Serruys PW, de Jaegere P, Kiemeneij F, Macaya C, Rutsch W, Heyndrickx G, Emanuelsson H, Marco J, Legrand V, Materne P et al. A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group. N Engl J Med. 1994. Aug 25 ; 331(8) : 489-95. https://doi.org/10.1056/NEJM199408253310801
  24. Zhang HS, Wang SQ. Ginsenoside Rg1 inhibits tumor necrosis factor-alpha (TNF-alpha)-induced human arterial smooth muscle cells (HASMCs) proliferation. J Cell Biochem. 2006. Aug 15 ; 98(6) : 1471-81. https://doi.org/10.1002/jcb.20799
  25. Ross R. Cell biology of atherosclerosis. Annu Rev Physiol. 1995 ; 57 : 791-804. https://doi.org/10.1146/annurev.ph.57.030195.004043
  26. Chandrasekar B, Mummidi S, Mahimainathan L, Patel DN, Bailey SR, Imam SZ, Greene WC, Valente AJ. Interleukin-18-induced human coronary artery smooth muscle cell migration is dependent on NF-kappaB- and AP-1-mediated matrix metalloproteinase-9 expression and is inhibited by atorvastatin. J Biol Chem. 2006 ; 281(22) : 15099-109. https://doi.org/10.1074/jbc.M600200200
  27. Rouis M. Matrix metalloproteinases: a potential therapeutic target in atherosclerosis. Curr Drug Targets Cardiovasc Haematol Disord. 2005. Dec ; 5(6) : 541-8. https://doi.org/10.2174/156800605774961979
  28. Cohen JJ, Duke RC, Fadok VA, Sellins KS. Apoptosis and programmed cell death in immunity. Annu Rev Immunol. 1992 ; 10 : 267-93. https://doi.org/10.1146/annurev.iy.10.040192.001411
  29. Heo SK, Yun HJ, Park WH, Park SD. Emodin inhibits TNF-alpha-induced human aortic smoothmuscle cell proliferation via caspase- and mitochondrialdependent apoptosis. J Cell Biochem. 2008. Sep 1 ; 105(1) : 70-80. https://doi.org/10.1002/jcb.21805
  30. Jourdain A, Martinou JC. Mitochondrial outermembrane permeabilization and remodelling in apoptosis. Int J Biochem Cell Biol. 2009. Oct ; 41(10) : 1884-9. https://doi.org/10.1016/j.biocel.2009.05.001
  31. Rouis M. Matrix metalloproteinases: a potential therapeutic target in atherosclerosis. Curr Drug Targets Cardiovasc Haematol Disord. 2005. Dec ; 5(6) : 541-8. https://doi.org/10.2174/156800605774961979
  32. Cho A, Reidy MA. Matrix metalloproteinase-9 is necessary for the regulation of smooth muscle cell replication and migration after arterial injury. Circ Res. 2002 ; 91(9) : 845-51. https://doi.org/10.1161/01.RES.0000040420.17366.2E