Screening of Anti-atherosclerotic Effect of Lonicera Flower by Antioxidative and Anti-thrombotic Mechanism

Lonicera Flower의 항산화활성과 LDL 산화 억제효과 및 혈전용해능에 관한 연구

  • Ju, Shin-Tak (Cardiovascular Medical Research Center and Department of Diagnostics, College of Oriental Medicine, Dongguk University) ;
  • Lee, Min-Ja (Cardiovascular Medical Research Center and Department of Diagnostics, College of Oriental Medicine, Dongguk University) ;
  • Lee, Hye-Sook (Cardiovascular Medical Research Center and Department of Diagnostics, College of Oriental Medicine, Dongguk University) ;
  • Jung, Hyun-Jung (Cardiovascular Medical Research Center and Department of Diagnostics, College of Oriental Medicine, Dongguk University) ;
  • Kim, Hyuck (Cardiovascular Medical Research Center and Department of Diagnostics, College of Oriental Medicine, Dongguk University) ;
  • Kim, Jai-Eun (Cardiovascular Medical Research Center and Department of Pathology, College of Oriental Medicine, Dongguk University) ;
  • Park, Sun-Dong (Cardiovascular Medical Research Center and Department of Prescriptionology, College of Oriental Medicine, Dongguk University) ;
  • Park, Won-Hwan (Cardiovascular Medical Research Center and Department of Diagnostics, College of Oriental Medicine, Dongguk University)
  • 주신탁 (동국대학교 한의과대학 기초의과학연구센터 & 진단학교실) ;
  • 이민자 (동국대학교 한의과대학 기초의과학연구센터 & 진단학교실) ;
  • 이혜숙 (동국대학교 한의과대학 기초의과학연구센터 & 진단학교실) ;
  • 정현정 (동국대학교 한의과대학 기초의과학연구센터 & 진단학교실) ;
  • 김혁 (동국대학교 한의과대학 기초의과학연구센터 & 진단학교실) ;
  • 김재은 (동국대학교 한의과대학 기초의과학연구센터 & 병리학교실) ;
  • 박선동 (동국대학교 한의과대학 기초의과학연구센터 & 방제학교실) ;
  • 박원환 (동국대학교 한의과대학 기초의과학연구센터 & 진단학교실)
  • Published : 2008.12.25

Abstract

The flowers and buds of Lonicera Flower (LF), are used in Korean herbal medicine for latent-heat-clearing, antipyretic, detoxicant and anti-inflammatory ailments. This plant is used worldwide for the treatment of many types of inflammatory disease including respiratory infections, diabetes mellitus, rheumatoid arthritis and play an important role in immune reaction. These pharmaceutical effects of LF looks like to be related to its antioxidant capacity and phytochemicals containing in LF. In this study, the antioxidant activity of extract from LF was studied in vitro methods by measuring the antioxidant activity by TEAC, measuring the scavenging effects on reactive oxygen species (ROS) [superoxide anion, hydroxyl radical] and on reactive nitrogen species (RNS) [nitric oxide and peroxynitrite] as well as measuring the inhibitory effect on $Cu^{2+}$ induced human LDL oxidation and the inhibitory effect on collagen induced platelet aggregation. The LF extracts were found to have a potent scavenging activity, as well as an inhibitory effect on LDL oxidation and on platelet aggregation. In conclusion, the LF extracts have anti-oxidative and anti-atherosclerotic effects in vitro system, which can be used for developing pharmaceutical drug against oxidative stress and atherosclerosis.

Keywords

References

  1. 전국한의과대학본초학교수 공편저. 본초학. 영림사, p 198, 2000.
  2. 지형준, 이상인 편저. 대한약전외 한약(생약)규격집 주해서. 한국메디칼인덱스사, pp 87-88, 1988.
  3. 한방약리학 교재편찬위원회 저. 한방약리학. 신일상사, pp 133-134, 2006.
  4. 김철호 저. 한약약리학. 집문당, pp 150-151, 2001.
  5. Lee, J.N., Jeong, S.I., Jang, S.I. Effects of aqueous extract from Lonicera japonica flower on trimellitic anhydride-induced contact hypersensitivity in BALB/c Mice. Kor. J. Herbology. 23(2):51-58, 2008.
  6. Yun, Y.G., Kim, G.M., Lee, S.J., Ryu, S.H., Jang, S.I. Inhibitory effect of aqueous extract from Lonicera japonica flower on LPS-induced inflammatory mediators in RAW 264.7 macrophages. Kor. J. Herbology. 22(3):117-125, 2007.
  7. Xu, Y., Oliverson, B.G., Simmons, D.L. Trifunctional inhibition of COX-2 by extracts of Lonicera japonica: Direct inhibition, transcriptional and post-transcriptional down regulation. Journal of Ethnopharmacology. 111(3):667-670, 2007. https://doi.org/10.1016/j.jep.2007.01.017
  8. Park, H.S. The effects of anti-cancer response of Lonicerae Flos herbal-acupuncture. The Journal of Korean Acupuncture & Moxibustion Society. 22(5):91-97, 2005.
  9. Bae, J.H., Kim, M.S., Kang, E.H. Antimicrobial effect of Lonicerae Flos extracts on food-borne pathogens. KOREAN J. FOOD SCI. TECHNOL. 37(4):642-647, 2005.
  10. Giles, G.I., Tasker, K.M., Jacob, C. Hypothesis: the role of reactive sulfur species in oxidative stress. Free Radical Biology & Medicine, 31: 1279-1283, 2001. https://doi.org/10.1016/S0891-5849(01)00710-9
  11. Espey, M.G., Miranda, K.M., Thomas, D.D., Xavier, S., Citrin, D., Vitek, M.P., David A.W. A chemical perspective on the interplay between NO, reactive oxygen species, and reactive nitrogen oxide species. Ann. N. Y Acad. Sci. 962: 195-206, 2002. https://doi.org/10.1111/j.1749-6632.2002.tb04068.x
  12. Fubini, B., Hubbard, A. Reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation by silica in inflammation and fibrosis. Free Radical Biology & Medicine, 34: 1507-1516, 2003. https://doi.org/10.1016/S0891-5849(03)00149-7
  13. 2006년 사망원인 통계 결과, 통계청 http://www.nso.go.kr
  14. Elisaf, M. The treatment of coronary heart disease: an update. Part 1: An overview of the risk factors for cardiovascular disease. Curr. Med. Res. Opin., 17(1):18-26, 2001.
  15. Raya, A.A., Raya, S.A. Inflammation: A pivotal link between autoimmune diseases and atherosclerosis. Autoimmunity Reviews, 5: 331-337, 2006. https://doi.org/10.1016/j.autrev.2005.12.006
  16. Verstraeta, M., Lijnen, H.R., Collen, D. Thrombolytic agents in development. Drugs, 50: 29-42, 1995. https://doi.org/10.2165/00003495-199550010-00003
  17. Nakajima, N., Mihara, H., Sumi, H. Characterization of potent fibrinolytic enzymes in earthworm, Lumbricus rubellus. Biosci. Biotechnol. Biochem. 57: 1726-1730, 1993. https://doi.org/10.1271/bbb.57.1726
  18. Roberta, R.E., Pellegrini, N., Proteggente, A., Pannala, A., Yang, M., Rice-Evans, C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radical Biology & Medicine, 26: 1231-1237, 1999. https://doi.org/10.1016/S0891-5849(98)00315-3
  19. Miller, N.J., Rice-Evans, C., Davies, M.J., Gopinathan, V., Milner, A.A. A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin. Sci. 84: 407-412, 1993. https://doi.org/10.1042/cs0840407
  20. Blois, M.S. Antioxidant determination by the use of stable free radical. Nature, 26: 1199-1200, 1958.
  21. Gotoh, N. and Niki, E. Rates of interactions of superoxide with vitamin E, vitamin C and related compounds as measured by chemiluminescence. Biochem. Biophys. Acta, 1115: 201-207, 1992. https://doi.org/10.1016/0304-4165(92)90054-X
  22. Halliwell, B. & Gutteridge, J.M. Role of free radicals and catalytic metalions in human disease: an overview. Method Enzymol. 186: 1-85, 1990. https://doi.org/10.1016/0076-6879(90)86093-B
  23. Nagata, N., Momose, K. & Ishida, Y. Inhibitory effects of catecholamines and anti-oxidants on the fluorescence reactionof 4,5-diaminofluorescein, DAF-2, a novel indicator of nitric oxide. J. Biochem. Tokyo, 125: 658-661, 1999. https://doi.org/10.1093/oxfordjournals.jbchem.a022333
  24. Crow, J.P. Dichlorodihydrofluorescein and dihydro- rhodamine 123 are sensitive indicators of peroxynitrite in vitro: implications for intracellular measurement of reactive nitrogen and oxygen species. Nitric Oxide, 1: 145-157, 1997. https://doi.org/10.1006/niox.1996.0113
  25. Yoon, M.A., Jeong, T.S., Park, D.S., Xu, M.Z., Oh, H.W., Song, K.B., Lee, W.S. and Park, H.Y. Antioxidant effect of quinoline alkaloid and 2,4-di-tert-butylphenol isolated from Scolopendra subspinipes. Biol. Pharm. Bull. 29: 735-739, 2006. https://doi.org/10.1248/bpb.29.735
  26. Yagi, K.A. Simple fluometric assay for lipoperoxide in blood plasma. Biochem. Med. 15: 212-216, 1976. https://doi.org/10.1016/0006-2944(76)90049-1
  27. Astrup, T. and Mullertz, S. The fibrin method for estimating of fibrinolytic activity. Arch. Biochem. Biophys. 40: 346-351, 1952. https://doi.org/10.1016/0003-9861(52)90121-5
  28. Fogliano, V., Verde, V., Randazzo, G., Ritieni, A. Method for measuring antioxidant activity and its application to monitoring the antioxidant capacity of wines. J. Agric. Food Chem. 47: 1035-1040, 1999. https://doi.org/10.1021/jf980496s
  29. Nicoletta, P., mauro, S., Barbara, C., Daniele, DR., Sara, S., Marta B., and Furio, B. Total antioxidant capacity of plant foods, beverages and oils consumed in italy assessed by three different in vitro assays. J. Nutr. 133: 2812-2819, 2003. https://doi.org/10.1093/jn/133.9.2812
  30. 남석현, 강미영. 한약재 열수추출물의 항산화효과 검정. 한국농화학회지 43: 141-147, 2000.
  31. Sanchez, C.S., Gonzalez, A.M.T., Garcia-Parrilla, M.C., Granados, J.J.Q., Serrana, H.L.G., Martinez, M.C.L. Different radical scavenging tests in virgin olive oil and their relation to the total phenol content. Anal. Chim. Acta., 593: 103-107, 2007. https://doi.org/10.1016/j.aca.2007.04.037
  32. Chung, S.K. Hydroxyl radical scavenging effects of spices and scavengers from brown mustard. Biosci. Biotech. Biochem. 61: 118-123, 1997. https://doi.org/10.1271/bbb.61.118
  33. Lee, S.O., Lee, H.J., Yu, M.H., Im, H.G., Lee, I.S. Total polyphenol contents and antioxidant activities of methanol extracts from vegetables produced in Ullung Island. Korean J. Food Sci. Technol. 37: 233-240, 2005.
  34. Lee, O.H., Lee, H.B., Son, J.Y. Antimicrobial activities and nitrite scavenging ability of olive leaf fracrions. Korean J. Soc. Food Cook. Sci. 20: 204-210, 2004.
  35. Park, C.S. Antioxidative and nitrite scavenging abilities of medicinal plant extracts. Korean J. Food Preserv. 12: 631-636, 2005.
  36. Channon, K.M., Qian, H., George, S.E. Nitric oxide synthase in atherosclerosis and vascular injury: insights from experimental gene therapy. Arterioscler. Thromb. Opinion in Pharmacology, 4: 110-115, 2004. https://doi.org/10.1016/j.coph.2003.12.004
  37. Virag, L., Szabo, E., Gergely, P., Szabo, C. Peroxynitrite induced cytotoxicity: metabolism and opportunities for intervention, Toxocol. Lett. pp 140-141, 113-124, 2003.
  38. Lee, H.J., Kim, Y.A., Ahn, J.W., Lee, B.J., Moon, S.G., Seo, Y.W. Screening of peroxynitrite and DPPH radical scavenging activities from salt marsh plants. Korean J. Biotechnol. Bioeng. 19: 57-61, 2004.
  39. Berliner, J.A., Heinecke, J.W. The role of oxidized lipoproteins in atherogenesis. Free Radic. Biol. Med. 20: 707-727, 1996. https://doi.org/10.1016/0891-5849(95)02173-6
  40. Raya, A.A., Raya, S.A. Inflammation: A pivotal link between autoimmune diseases and atherosclerosis. Autoimmunity Reviews, 5: 331-337, 2006. https://doi.org/10.1016/j.autrev.2005.12.006
  41. Yokoyama, M. Oxidant stress and atherosclerosis. Current Opinion in Pharmacology, 4: 110-115, 2004. https://doi.org/10.1016/j.coph.2003.12.004
  42. Zhenbao, J., Fei, T., Ling, G., Guanjun, Tao, Xiaolin, Ding. Antioxidant properties of extracts from juemingzi (Cassia tora L.) evaluated in vitro. LWT - Food Science and Technology, 40: 1072-1077, 2007. https://doi.org/10.1016/j.lwt.2006.05.010
  43. Packham, M.A. Role of platelets in thrombosis and hemostasis. Can. J. of Physiol. Pharmacol, 72: 278-284, 1994. https://doi.org/10.1139/y94-043