Journal of Applied Biological Chemistry

  • 제52권4호
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  • Pages.187-194
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  • 2009
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  • 1976-0442(pISSN)
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  • 2234-7941(eISSN)
한국응용생명화학회 (The Korean Society for Applied Biological Chemistry)
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참당귀(Angelica gigas)에서 분리한 pyranocurmarin 성분의 ACAT 저해활성 및 참당귀 부위별 pyranocurmarin 성분의 함량 분석

ACAT (Acyl-CoA:cholesterol Acyltransferase) Inhibitory Effect and Quantification of Pyranocurmarin in Different Parts of Angelica gigas Nakai

  • 김금숙 (농촌진흥청 국립원예특작과학원 인삼특작부) ;
  • 박춘근 (농촌진흥청 국립원예특작과학원 인삼특작부) ;
  • 정태숙 (한국생명공학연구원) ;
  • 차선우 (농촌진흥청 국립원예특작과학원 인삼특작부) ;
  • 백남인 (경희대학교 생명공학원) ;
  • 송경식 (경북대학교 농업생명과학대학)
  • Kim, Geum-Soog (Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, RDA) ;
  • Park, Chun-Geun (Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, RDA) ;
  • Jeong, Tae-Sook (Korea Research Institute of Bioscience & Biotechnology) ;
  • Cha, Seon-Woo (Department of Herbal Crop Research, National Institute of Horticultural & Herbal Science, RDA) ;
  • Baek, Nam-In (Graduate School of Biotechnology, Kyung Hee University) ;
  • Song, Kyung-Sik (College of Agriculture and Life Sciences, Kyungpook National University)
  • 발행 : 2009.12.31
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초록

참당귀 뿌리로부터 2종의 pyranocoumarin 성분을 분리하고 그들의 구조는 NMR 분석에 의해 각각 decursinol angelate(1), decursin(2)로 결정하였다. 이들 화합물에 대하여 hACAT 저해활성을 검정해본 결과, decursinol angelate(1)가 약한 저해활성을 나타낸 반면 decursin(2)은 hACAT1와 hACAT2에 대하여 $IC_{50}$ 값이 각각 137, $168\;{\mu}M$로서 우수한 저해활성을 나타내었다. 한편, 참당귀의 뿌리를 비롯한 꽃, 종자, 잎 등 여러부위에서 decursinol angelate(1), decursin(2)를 정량분석하였는데, 이때 LC/MS/MS(ESI, positive ion mode, MRM mode) 분석을 이용하였다. Decursinol angelate의 함량은 뿌리>잎>종자>꽃 순으로 높았으며, decursin의 함량은 뿌리>종자>꽃>잎 순으로 높게 측정되었다. 이상의 결과들은, 참당귀의 decursin이 동맥경화와 같은 심혈관 질환의 개선과 치료를 위해 유용하게 이용될 수 있음을 시사하였다. 또한 뿌리 이외에 그 동안 이용되지 않고 있던 참당귀 꽃, 잎과 같은 비상용부위에도 기능성물질인 decursin, decursinol angelate이 상당량 함유되어 있음이 구명되어 이러한 부위도 새로운 천연 기능성 소재로서 활용될 수 있음을 기대할 수 있었다.

Two pyranocoumarin constituents have been isolated from Angelica gigas and were identified as decursinol angelate (1) and decursin (2) by means of NMR analysis, respectively. Human acyl-CoA:cholesterol acyltransferase (hACAT) inhibitory activity of decursinol angelate (1) and decursin (2) was evaluated. Decursin (2) showed significantly inhibitory activity against hACAT1 and hACAT2 with $IC_{50}$ value of 137 and $168\;{\mu}M$, respectively, whereas decursinol angelate (1) exhibited weak ACAT inhibitory activity. These results suggested that decusin from A. gigas might be effective for the prevention and the treatment of hypercholesterolemia or atherosclerosis by inhibitory effect on hACAT. The contents of decursinol angelate (1) and decursin (2) were analyzed in various parts of A. gigas including flower, seed, leaf and root using LC/MS/MS (ESI, positive ion mode, MRM mode). The content of decursinol angelate was increased in order of flower, seed, leaf, and root and decursin content was increased in order of flower, seed, leaf, and root. It was expected that unused parts including leaf and flower of A. gigas might be useful as new functional sources by their high contents of decursin and decursinol angelate.

키워드

참고문헌

  1. Brecher P and Chan CT (1980) Properties of Acyl-coA:cholesterol O-acyltransferase in aortic microsomes from atherosclerotic rabbits. BBA-Lipid Lipid Met 617, 458-471 https://doi.org/10.1016/0005-2760(80)90012-0
  2. Chi HJ and Kim HS (1970) Studies on the components of Umbelliferae plants in Korea: pharmacological study of decursin, decursinol and nodakenin. Kor J Pharmacogn 1, 25-32
  3. Cho KH, An S, Lee WS, Paik YK, Kim YK, and Jeong TS (2003) Mass-production of human ACAT-1 and ACAT-2 to screen isoform-specific inhibitor: a different substrate specificity and inhibitory regulation. Biochem Biophys Res Commun 309, 864-872 https://doi.org/10.1016/j.bbrc.2003.08.077
  4. Dong J, Atwood CS, Anderson VE, Siedlak SL, Smith MA, Perry G, and Carey PR (2003) Metal binding and oxidation of amyloid-$\hat{a}$ within isolated senile plaque cores: Raman microscopic evidence. Biochemistry 42, 2768-2773 https://doi.org/10.1021/bi0272151
  5. Epifano F, Molinaro G, Genovese S, Ngomba RT, Nicoletti F, and Curini M (2008) Neuroprotective effect of prenyloxycoumarins from edible vegetables. Neurosci Lett 443, 57-60 https://doi.org/10.1016/j.neulet.2008.07.062
  6. Han SB, Kim YH, Lee CW, Park SM, Lee HY, Ahn KS, Kim IH, and Kim HM (1998) Characteristic immunostimulation by angelan isolated from Angelica gigas Nakai. Immunopharmacology 40, 39-48 https://doi.org/10.1016/S0162-3109(98)00026-5
  7. Hua DH, Huang XD, Tamura M, Chen Y, Woltkamp M, Jin LW, Perchellet EM, Perchellet JP, Chiang PK, Namatame I, and Tomoda H (2003) Syntheses and bioactivities of tricyclic pyrones. Tetrahedron 59, 4795-4803 https://doi.org/10.1016/S0040-4020(03)00687-2
  8. Hutter-Paier B, Huttunen HJ, Puglielli L, Eckman CB, Kim DY, Hofmeister A, Moir RD, Domnitz SB, Frosch MP, Windisch M, and Kovacs DM (2004) The ACAT inhibitor CP-113,818 markedly reduces amyloid pathology in a mouse model of Alzheimer's disease. Neuron 44, 227-238 https://doi.org/10.1016/j.neuron.2004.08.043
  9. Kang SA, Han JA, Jang KH, and Choue RW (2004) DPPH radical scavenger activity and antioxidant effects of Cham-Dang-Gui (Angilica gigas). J Korean Soc Food Sci Nutr 33, 1112-1118 https://doi.org/10.3746/jkfn.2004.33.7.1112
  10. Kang SY and Kim YC (2007) Neuroprotective coumarins from the root of Angelica gigas: Structure-activity relationships. Arch Pharm Res 30, 1368-1373 https://doi.org/10.1007/BF02977358
  11. Kil JS, Kim MG, Choi HM, Lim JP, Boo YM, Kim EH, Kim JB, Kim HK, and Leem KH (2008) Inhibitory effects of Angelicae Gigantis Radix on osteoclast formation. Phytother Res 22, 472-476 https://doi.org/10.1002/ptr.2342
  12. Kim HM, Kang JS, Park SK, Lee K, Kim JY, Kim YJ, Hong JT, Kim Y, and Han SB (2008) Antidiabetic activity of angelan Isolated from Angelica gigas Nakai. Arch Pharm Res 31, 1489-1496 https://doi.org/10.1007/s12272-001-2135-9
  13. Kim JH, Jeong JH, Jeon ST, Kim H, Ock J, Suk K, Kim SI, Song KS, and Lee WH (2006) Decursin inhibits induction of inflammatory mediators by blocking nuclear factor-kappa B activation in macrophages. Mol Pharmacol 69, 1783-1790 https://doi.org/10.1124/mol.105.021048
  14. Konoshima M, Chi HJ, and Hata K (1968) Coumarins from the root of Angelica gigas Nakai. Chem Pharm Bull 16, 1139-1140
  15. Lawrence LR and Gregory SS (2000) Cholesterol esters and atherosclerosisa game of ACAT and mouse. Nat Med 6, 1341-1347 https://doi.org/10.1038/82153
  16. Lee CH, Jeong TS, Choi YK, Hyun BW, Oh GT, Kim EH, Kim JR, Han JI, and Bok SH (2001) Anti-atherogenic effect of citrus flavonoids, naringin and naringenin, associated with hepatic ACAT and aortic VCAM-1 and MCP-1 in high cholesterol-fed rabbits. Biochem Biophys Res Commun 284, 681-688 https://doi.org/10.1006/bbrc.2001.5001
  17. Lee S, Shin DS, Kim JS, Oh KB, and Kang SS (2003a) Antibacterial coumarins from Angelica gigas roots. Arch Pharm Res 26, 449-452 https://doi.org/10.1007/BF02976860
  18. Lee SH, Lee YS, Jung SH, Shin KH, Kim BK, and Kang SS (2003b) Antioxidant Activities of Decursinol Angelate and Decursin from Angelica gigas Roots, Nat Prod Sci 9, 170-173
  19. Lee SL (1994) In Phytology, pp.578-580. Young Lim Pubishing Co., Seoul, Korea
  20. Li L, Cao D, Garber DW, Kim H, and Fukuchi KI (2003) Association of Aortic Atherosclerosis with Cerebral - Amyloidosis and Learning Deficits in a Mouse Model of Alzheimer's Disease. Am J Pathol 163, 2155-2164 https://doi.org/10.1016/S0002-9440(10)63572-9
  21. Lovell MA, Robertson JD, Teesdale WJ, Campbell JL, and Markesbery WR (1998) Copper, iron and zinc in Alzheimer's disease senile plaques. J Neurol Sci 158, 47-52 https://doi.org/10.1016/S0022-510X(98)00092-6
  22. Pappolla MA, Smith MA, Bryant-Thomas T, Bazan N, Petanceska S, Perry G, Thal LJ, Sano M, and Refolo LM (2002) Cholesterol, oxidative stress, and Alzheimer's disease: expanding the horizons of pathogenesis. Free Radic Biol Med 33, 173-181 https://doi.org/10.1016/S0891-5849(02)00841-9
  23. Park KW, Choi SR, Hong HR, Kim JY, Shon MY, and Seo KI (2007a) Biological activities of methanol extract of Angelica gigas Nakai. Korean J Food Preserv 14, 655-661
  24. Park KW, Choi SR, Shon MY, Jeong IY, Kang KS, Lee ST, Shim KH, and Seo KI (2007b) Cytotoxic effects of decursin from Angelica gigas Nakai in human cancer cells. J Korean Soc Food Sci Nutr 36, 1385-139 https://doi.org/10.3746/jkfn.2007.36.11.1385
  25. Puglielli L, Konopka G, Pack-Chung E, Ingano LAM, Berezovska O, Hyman BT, Chang TY, Tanzi RE, and Kovacs DM (2001) Acyl-coenzyme A: cholesterol acyltransferase modulates the generation of the amyloid -peptide. Nat Cell Biol 3, 905-912 https://doi.org/10.1038/ncb1001-905
  26. Puglielli L, Tanzi RE, and Kovacs DM (2003) Alzheimer's disease: the cholesterol connection. Nat Neurosci 6, 345-351 https://doi.org/10.1038/nn0403-345
  27. Refolo LM, Pappolla MA, Malester B, LaFrancois J, Bryant-Thomas T, Wang R, Tint GS, Sambamurti K, and Duff K (2000) Hypercholesterolemia accelerates the Alzheimer's amyloid pathology in a transgenic mouse model. Neurobiol Dis 7, 321-331 https://doi.org/10.1006/nbdi.2000.0304
  28. Rudel LL, Lee RG, and Cockman TL (2001) Acyl coenzyme A:cholesterol acyltransferase types 1 and 2: structure and function in atherosclerosis. Curr Opin Lipidol 12, 121-127 https://doi.org/10.1097/00041433-200104000-00005
  29. Runz H, Rietdorf J, Tomic I, de Bernard M, Beyreuther K, Pepperkok R, and Hartmann T (2002) Inhibition of intracellular cholesterol transport alters presenilin localization and amyloid precursor protein processing in neuronal cells. J Neurosci 22, 1679-1689
  30. Ryu KS, Hong ND, Kim NJ, and Kong YY (1990) Studies on the coumarin constituents of the root of Angelica gigas Nakai-Isolation of decursinol angelate and assay of decursinol angelate and decursin. Kor J Pharmacogn 21, 64-68
  31. Sarker SD and Nahar L (2004) Natural medicine: the genus Angelica. Curr Med Chem 11, 1479-1500 https://doi.org/10.2174/0929867043365189
  32. Seo YJ, Kwon MS, Park SH, Sim YB, Choi SM, Huh GH, Lee JK, and Suh HW (2009) The analgesic effect of decursinol. Arch Pharm Res 32, 937-943 https://doi.org/10.1007/s12272-009-1617-z
  33. Shin S, Jeon JH, Park D, Jang JY, Joo SS, Hwang BY, Choe SY,and Kim YB (2009) Anti-Inflammatory effects of an ethanolextract of Angelica gigas in a carrageenan-airp pouch inflammation model. Exp Anim 58, 431-436 https://doi.org/10.1538/expanim.58.431
  34. Son SH, Kim MJ, Chung WY, Son JA, Kim YS, Kim YC, Kang SS, Lee SK, and Park KK (2009) Decursin and decursinol inhibit VEGF-induced angiogenesis by blocking the activation of extracellular signal-regulated kinase and c-Jun N-terminal kinase. Cancer Lett 280, 86-92 https://doi.org/10.1016/j.canlet.2009.02.012
  35. Song GY, Lee JH, Cho M, Park BS, Kim DE, and Oh S (2007) Decursin suppresses human androgen-independent PC3 prostate cancer cell proliferation by promoting the degradation of betacatenin. Mol Pharmacol 72, 1599-1606 https://doi.org/10.1124/mol.107.040253
  36. Song MC, Yang HJ, Jeong TS, Kim KT, and Baek NI (2008) Heterocyclic compounds from Chrysanthemum coronarium L. and their inhibitory activity on hACAT-1, hACAT-2, and LDLoxidation. Arch Pharm Res 31, 573-578 https://doi.org/10.1007/s12272-001-1195-4
  37. Song SH, Seo BI, Kim HK, and Park JH (2004) The effects of angelicae gigantis radix extract on hydrocortisone acetate induced model of blood stasis. Kor J Herbol 19, 13-21
  38. Yan JJ, Kim DH, Moon YS, Jung JS, Ahn EM, Baek NI, and Song DK (2004) Protection against beta-amyloid peptideinduced memory impairment with long-term administration of extract of Angelica gigas or decursinol in mice. Prog Neuropsychopharmacol Biol Psychiat 28, 25-30 https://doi.org/10.1016/S0278-5846(03)00168-4
  39. Yim D, Singh RP, Agarwal C, Lee S, Chi H, and Agarwal R (2005) A novel anticancer agent, decursin, induces G(1) arrest and apoptosis in human prostate carcinoma cells. Cancer Res 65, 1035-1044

피인용 문헌

  1. Anti-inflammatory Effect of Angelicae Gigantis Radix Water Extract on LPS-stimulated Mouse Macrophages vol.28, pp.5, 2013, https://doi.org/10.6116/kjh.2013.28.5.113
  2. 천궁 및 당귀를 함유한 한방처방제 휘발성 향기추출물의 항염증 효과 vol.37, pp.3, 2009, https://doi.org/10.15230/scsk.2011.37.3.199