Effects of Supercritical Fluid Marc Extracts from Actinidia polygama Max. on Inflammation and Atherosclerosis

개다래 초임계 박추출물이 염증 및 동맥경화에 미치는 영향

  • Yu, Mi-Hee (Department of Food Science and Technology, Keimyung University) ;
  • Chae, In-Gyeong (Department of Food Science and Technology, Keimyung University) ;
  • Choi, Jun-Hyeok (Korea Food Research Institute) ;
  • Im, Hyo-Gwon (Department of Food Science and Technology, Keimyung University) ;
  • Choi, Hee-Don (Korea Food Research Institute) ;
  • Yang, Seun-Ah (The Center for Traditional Microorganism Resources, Keimyung University) ;
  • Lee, Jin-Ho (The Center for Traditional Microorganism Resources, Keimyung University) ;
  • Lee, In-Seon (Department of Food Science and Technology, Keimyung University)
  • 유미희 (계명대학교 식품가공학) ;
  • 채인경 (계명대학교 식품가공학) ;
  • 최준혁 (한국식품연구원) ;
  • 임효권 (계명대학교 식품가공학) ;
  • 최희돈 (한국식품연구원) ;
  • 양선아 (계명대학교 전통미생물자원개발 및 산업화연구(TMR)센터) ;
  • 이진호 (계명대학교 전통미생물자원개발 및 산업화연구(TMR)센터) ;
  • 이인선 (계명대학교 식품가공학)
  • Received : 2010.02.16
  • Accepted : 2010.04.23
  • Published : 2010.08.31

Abstract

The fruit of Actinidia polygama, Mock-chun-ryo in Korea, has been used as traditional medicine for abdominal pain, rheumatic arthritis, and stroke. In a previous study, the ethanol extract of A. polygama Max. showed antiinflammatory activity in RAW 264.7 cells. In this study, we investigated the anti-inflammatory and anti-atherosclerosis effects of supercritical fluid marc extracts from A. polygama Max. Anti-inflammatory extracts were produced from supercritical fluid extraction of the silver vine under the following conditions; pressure, 1,500-4,500 psi, temperature $35-55^{\circ}C$ and extraction time 1-2 hr. To evaluate the anti-inflammatory and anti-atherosclerotic effects of the extracts, we studied nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$), and tumor necrosis factor-alpha (TNF-$\alpha$) levels in RAW 264.7 cells and MMP-9 activity in human aortic smooth muscle cells (HASMC). The Marc 11 extract inhibited the production of NO, $PGE_2$, and TNF-$\alpha$ by lipopolysaccharide in RAW 264.7 cells. Moreover, the marc 11 extract inhibited TNF-$\alpha$-induced MMP-9 activity in HASMC. These results indicate that the Marc 11 extract of A. polygama Max. has the potential for use as an anti-atherosclerosis agent.

개다래(Actinidia polyama Max.)는 복통, 류마티스 관절염, 뇌졸중 치료에 사용되었으며, 최근 소염, 진통, 통풍에 효과가 있다고 알려져 있으나 특유의 강한 향과 맛을 지니고 있어 기능성 식품이나 치료용 약물을 개발하고자 할 때 많은 제약이 따른다. 따라서 개다래를 초임계 추출하여 향과 맛을 개선하고, 본 연구에서는 초임계추출 후 남은 부산물을 이용하여 (박)추출물을 제조하고 항염증 및 항동맥경화 활성을 조사하였다. 개다래 주정 추출물 및 초임계 박 추출물의 NO 소거활성을 비교한 결과, 개다래박 11 추출물 10, $100\;{\mu}g/mL$의 농도에서 36.63, 79.58%의 NO 소거활성을 보여 주정 추출물(4.61, 19.00%)에 비해 훨씬 높은 NO 소거활성을 보였다. 또한 RAW 264.7 세포주에 개다래 초임계 박 11 추출물을 처리하고, LPS를 처리하여 염증을 유발한 후 염증인자인 $PGE_2$의 생성, 그리고 proinflammatory cytokines인 TNF-$\alpha$의 생성량을 측정한 결과, 개다래 박 11 추출물은 LPS로 유도된 염증 인자들을 효과적으로 감소시키는 것으로 나타났다. 또한 박 11 추출물의 MMP-9 활성에 미치는 영향을 알아보기 위해 zymography를 실시한 결과, 추출물 50, $100\;{\mu}g/mL$의 농도에서 MMP-9의 활성이 효과적으로 감소됨을 확인하였으며, MMP-9의 단백질 발현도 억제됨을 확인하였다. 결론적으로 개다래 박 11 추출물은 LPS로 유도된 염증 인자들을 효과적으로 감소시켰으며, TNF-$\alpha$에 의해 증가된 MMP-9의 활성을 억제하는 것으로 나타나 동맥경화를 비롯한 고혈압, 암, 당뇨, 관절염 등의 만성염증성 질환의 예방과 치료에 효과적으로 적용할 수 있을 것으로 생각된다.

Keywords

References

  1. Ross R. Atherosclerosis: An inflammatory disease. New Engl. J. Med. 340: 115-126 (1999) https://doi.org/10.1056/NEJM199901143400207
  2. Libby P, Ridker PM, Maseri A. Inflammation and atherosclerosis. Circulation 105: 1135-1143 (2002) https://doi.org/10.1161/hc0902.104353
  3. Kim HY, Park JY. Oxidative stress and atherosclerosis. J. Korean Soc. Endocrinol. 15: 1-14 (2000)
  4. Sekalska B. Aortic expression of monocyte chemotactic protein-1 (MCP-1) gene in rabbits with experimental atherosclerosis. Ann. Acad. Med. Stetin. 49: 79-90 (2003)
  5. Kodili R, Hajjou M, Berman AB, Bansal MB, Zhang S, Pan JJ, Schecter AD. Chemokines induce matrix metalloproteinase-2 through activation of epidermal growth factor receptor in arterial smooth muscle cells. Cardiovasc. Res. 69: 706-715 (2006) https://doi.org/10.1016/j.cardiores.2005.09.012
  6. Newby AC, Zaltsman AB. Molecular mechanism in intimal hyperplasia. J. Pathol. 190: 300-309 (2000) https://doi.org/10.1002/(SICI)1096-9896(200002)190:3<300::AID-PATH596>3.0.CO;2-I
  7. Cho A, Reidy MA. Matric metalloproteinase-9 is necessary for the regulation of smooth muscle cell replication and migration after arterial injury. Circ. Res. 91: 845-851 (2002) https://doi.org/10.1161/01.RES.0000040420.17366.2E
  8. Lin SJ, Lee IT, Chen YH, Lin Fy, Sheu LM, Ku HH, Shiao MS, Chen JM, Chen YL. Salvianolic acid B attenuates MMP-2 and MMP-9 expression in vivo in apolipoprotein-E-deficient mouse aorta and in vitro in LPS-treated human aortic smooth muscle cells. J. Cell Biochem. 22: 372-384 (2007)
  9. Jung BS, Shin MG. Hyangyak-Dictionary. Younglimsa, Seoul, Korea. p. 386 (1990)
  10. Park EH, Kahn JH. Supressive effects of propolis in rat adjuvant arthritis. Arch. Pharm. Res. 22: 554-558 (1999) https://doi.org/10.1007/BF02975325
  11. Kang HJ. Anti-inflammatory, analgesic, and hypouricemic activities of Actinidia polygama. MS thesis, Kyung Hee Univ. Seoul, Korea (2003)
  12. Bendeck MP, Irvin C, Reidy MA. Inhibition of matrix metalloproteinase activity inhibits smooth muscle cell migration but not neointimal thickening after arterial injury. Circ. Res. 78: 38-43 (1996) https://doi.org/10.1161/01.RES.78.1.38
  13. Wang S, Chen Y, He L, Yang Y, Chen J, Wang X. Inhibition of vascular smooth muscle cell poliferation by serum from rats treated orally with Gastrodia and Uncaria decoction. a traditional Chinese formulation. J. Ethnopharmacol. 114: 458-462 (2007) https://doi.org/10.1016/j.jep.2007.08.039
  14. Nathan C, Xi QW. Nitric oxide synthases: Roles, tolls, and controls. Cell 78: 915-918 (1994) https://doi.org/10.1016/0092-8674(94)90266-6
  15. Korhonen R, Lahti A, Kankaanranta H, Moilane, E. Nitric oxide production and signaling in inflammation. Curr. Drug Targets-Inflamm. Allergy 4: 471-479 (2005) https://doi.org/10.2174/1568010054526359
  16. Bertolini A, Ottani A, Sandrini M. Selective COX-2 inhibitors and dual acting anti-inflammatory drugs: Critical remarks. Curr. Med. Chem. 9: 1033-1043 (2002) https://doi.org/10.2174/0929867024606650
  17. Parente L, Perretti M. Advances in the pathophysiology of constitutive and inducible cyclooxygenases: Two enzymes in the spotlight. Biochem. Pharmacol. 65: 153-159 (2003) https://doi.org/10.1016/S0006-2952(02)01422-3
  18. Guha M, Mackman N. LPS induction of gene expression in human monocytes. Cell. Signal. 13: 85-94 (2001) https://doi.org/10.1016/S0898-6568(00)00149-2