한국식품과학회지 (Korean Journal of Food Science and Technology)

한국식품과학회 (Korean Society of Food Science and Technology)
권호 표지

Mouse에서의 quercetin 경구투여 후의 체내 농도 및 대사체 isorhamnetin의 농도변화

Tissue Concentrations of Quercetin and Its Metabolite Isorhamnetin Following Oral Administration of Quercetin in Mice

  • 박관하 (군산대학교 해양과학대학 수산생명의학과) ;
  • 주종재 (군산대학교 식품영양학과) ;
  • 최선남 (군산대학교 식품공학과)
  • Park, Kwan-Ha (Department of Aquatic Life Medicine, Kunsan National University) ;
  • Choo, Jong-Jae (Department of Food Science & Nutrition, Kunsan National University) ;
  • Choi, Sun-Nam (Department of Food Science & Engineering, Kunsan National University)
  • 발행 : 2005.02.28
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Quercetin을 50 및 100mg/kg의 용량으로 mouse에 경구투여 후 흡수, 대사 및 조직내 농도를 조사하였으며 일부의 시험은 비교를 위해 rat에서도 수행하였다. Quercetin은 mouse에서 신속히 흡수되어 l시간 후면 최고 혈장내 농도에 도달하였으며 4시간 후에는 현저하게 농도가 감소하였다. 주요 대사체인 isorhamnetin의 혈장내 농도도 신속하게 증가하였으나 quercetin 보다는 높은 농도로 유지되는 시간이 길었다. Rat에서 알려진 현상과 같이 quercetin이나 isorhamnetin 모두 유리상태로 존재하지 않고 대부분 glucuronide/sulfate의 포합체 형태로 존재하였다. Quercetin 및 isorhamnetin의 조직내 농도는 투여 1시간 및 6시간 콩히 간장>신장>비장>혈장의 순이었으며 이 순서는 rat에서도 마찬가지였다. 이 연구결과를 통해 mouse에서 quercetin이 경구투여 후 실제로 흡수되며 사람이나 다른 동물종에서 관찰된 것과 같이 quercetin은 신속하게 전환됨을 관찰하였다. 또한 이 결과는 mouse를 이용한 실험에서 지금까지 규명된 quercetin의 다양한 약리효과를 설명하는 데 필요한 자료의 역할을 할 수 있을 것이다.

Absorption, metabolism, and tissue concentrations of quercetin were examined and compared in mice and rats after oral administration of quercetin at 50 or 100 mg/kg. Quercetin was absorbed quickly in mice and reached maximum plasma concentration in I hr post-administration, and declined sharply after 4 hr. Plasma concentration of isorhamnetin, a major metabolite, also increased sharply, indicating rapid metabolic conversion, but elevated level was maintained longer than that of quercetin. Quercetin and isorhamnetin were found predominantly in glucuronide/sulfate-conjugate forms in both mice and rats. Tissue concentrations of quercetin and isorhamnetin in mice and rats were in the order of liver>kidney>spleen>plasma both 1 and 6 hr postadministration. These results show that quercetin is absorbed in mice after oral feeding and quickly metabolized into isorhamnetin as demonstrated in humans and other animal species. The results also can be used to explain various pharmacological activities reported in mouse models.

키워드

참고문헌

  1. Rice-Evans C, Miller NJ. Structure-antioxidant activity relationships of flavonoids and isoflavonoids. pp. 199-219. In: Flavonoids in Health and Disease, Rice-Evans C and Parker L (ed). Marcel Dekker, Inc., New York, USA (1998)
  2. Hertog MGL, Hollman PCH, van de Putte B. Contents of potentially anticarcinogenic flavonoids in tea infusions, wines, and fruit juices. J. Agric. Food Chem. 41: 1242-1246 (1993) https://doi.org/10.1021/jf00032a015
  3. Picinelli A, Suarez B, Mangas JJ. Analysis of polyphenols in apple products. Z. Lebensm. Unters. Forsch. A 204: 48-51 (1997) https://doi.org/10.1007/s002170050035
  4. Price KR, Rhodes MJC. Analysis of the major flavonol glycosides present in four varieties of onion (Allium cepa) and changes in composition resulting from autolysis. J. Sci. Food Agric. 74: 331-339 (1997) https://doi.org/10.1002/(SICI)1097-0010(199707)74:3<331::AID-JSFA806>3.0.CO;2-C
  5. Chen YC, Shen SC, Chow JM, Ko CH, Tseng SW. Flavone inhibition of tumor growth via apoptosis in vitro and in vivo. Int. J. Oncol. 25: 661-670 (2004)
  6. Edenharder R and Grunhage D. Free radical scavenging abilities of flavonoids as mechanism of protection against mutagenicity induced by tert-butyhydroperoxide or cumene hydro peroxide in Salmonella typhimurium TA102. Mut. Res. 9: 1-18 (2003)
  7. Pinot F, el Yaagoubi A, Christie P, Dinh-Xuan AT, Polla BS. Induction of stress proteins by tobacco smoke in human monocytes: modulation by antioxidants. Cell Stress Chaperone 2: 156-161 (1997) https://doi.org/10.1379/1466-1268(1997)002<0156:IOSPBT>2.3.CO;2
  8. Psotova J, Chlopcikova S, Miketova P, Hrbac J, Simanek V. Chemoprotective effects of plant phenolics against anthracyclineinduced toxicity on rat cardiomyocytes: Part III. Apigenin, baicalein, kaempherol, luteolin and quercetin. Phytother. Res. 18: 516-521 (2004) https://doi.org/10.1002/ptr.1462
  9. Daniel RS, Devi KS, Augusti KT, Sudhakaran Nair CR. Mechanism of actionof antiatherogenic and related effects of Ficus bengalensis Linn. flavonoids in experimental animals. Indian J. Exp. Biol. 41: 296-303 (2003)
  10. Duarte J, Perez-Palencia R, Vargas F, Ocete MA, Perez-Vizcaino F, Zarzuelo A, Tamargo J. Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats. Br. J. Pharmacol. 133: 117-124 (2001) https://doi.org/10.1038/sj.bjp.0704064
  11. Soloviev A, Stefanov A, Parshikov A, Khromov A, Moibenko A, Kvotchina L, Balavoine G, Geletii Y. Arrhythmogenic peroxynitrite-induced alterations in mammalian heart contractility and its prevention with quercetin-filled liposome. Cardiovasc. Toxicol. 2: 129-139 (2002) https://doi.org/10.1385/CT:2:2:129
  12. Kahraman A, Inal ME. Protective effects of quercetin on ultraviolet A light-induced oxidative stress in the blood of rat. J. Appl. Toxicol. 22: 303-309 (2002) https://doi.org/10.1002/jat.863
  13. Vessal M, Hemmati M, Vasei M. Antidiabetic effects of quercetin in streptozotocin-induced diabetic rats. Com. Biochem. Physiol. C 135: 357-364 (2003) https://doi.org/10.1016/S1095-6433(03)00090-4
  14. Mahesh T, Menon VP. Quercetin alleviates oxidative stress in streptozotocin-induced diabetic rats. Phytother. Res. 18: 123-127 (2004) https://doi.org/10.1002/ptr.1374
  15. De S, Chakraborty RN, Ghosh S, Sengupta A, Das S. Comparative evaluation of cancer chemopreventive efficacy of alpha-tocopherol and quercetin in a murine model. J. Exp. Clin. Cancer Res. 23: 251-258 (2004)
  16. Naidu PS, Kunkami SK. Quercetin, a bioflavonoid, reverse haloperidol-induced catalepsy. Methods Find. Exp. Clin. Pharmacol. 26: 323-326 (2004) https://doi.org/10.1358/mf.2004.26.5.831321
  17. Janbaz KH, Saeed SA, Gilani AH. Studies on the protective effects of caffeic acid and quercetin on chemical-induced hepatotoxicity in rodents. Phytomedicine 11: 424-430 (2004) https://doi.org/10.1016/j.phymed.2003.05.002
  18. Erlund I, Kosonen T, Alfthan G, Maenpaa, Perttunen K, Kenraali J, Aro A. Pharmacokinetics of quercetin from quercetin aglycone and rutin in healthy volunteers. Eur. J. Clin. Pharmacol. 56: 545-553 (2000) https://doi.org/10.1007/s002280000197
  19. Graefe EU, Derendorf H, Veit M. Pharamcokinetic and bioavailability of the flavol quercetin in humans. Int. J. Clin. Pharmacol. Therapy 37: 219-233 (1999)
  20. Ader P, Wessmann A, Wolffram S. Bioavailability and metabolism of the flavonol quercetin in the pig. Free Rad. Biol. Med. 28: 1056-1067 (2000) https://doi.org/10.1016/S0891-5849(00)00195-7
  21. Khaled KA, El-Sayed YM, Al-Hadiya BM. Disposition of the flavonoid quercetin in rats after single intravenous and oral doses. Drug Dev. Ind. Pharmcol. 29: 397-403 (2003) https://doi.org/10.1081/DDC-120018375
  22. Morrice PC, Wood SG, Duthie GG. High-performance liquid chromatographic determination of quercetin and isorhamnetin in rat tissues using $\beta$-glucuronidase and acid hydrolysis. J. Chromatogr. B 738: 413-417 (2000) https://doi.org/10.1016/S0378-4347(99)00520-4
  23. Piskula MK, Terao J. Quercetin solubility affects its accumulation in rats after oral administration. J. Agric. Food. Chem. 46: 4313-4317 (1998) https://doi.org/10.1021/jf980117v
  24. Wollenber E. Flavones and flavonols. pp. 189-259. In: The Flavonoids: Advances in Research. Harbone TJ and Marby TJ (ed). Chapman and Hall, London, UK (1982)
  25. Hollman PCH, Bijsman MNCP, van Gameren Y, Cnossen EJP, de Vries JHM, Katan MB. The sugar moeity is a major determinant of the absorption of dietary flavonoid glycosides in man. Free Rad. Res. 31: 569-573 (1999) https://doi.org/10.1080/10715769900301141
  26. Day AJ, Dupont MS, Ridley S, Rhodes M, Rhodes MJ, Morgan MR. Deglycosylation of flavonoid glycosides by human small intestine and liver beta-glucosidase activity. FEBS Lett. 436: 71-75 (1998) https://doi.org/10.1016/S0014-5793(98)01101-6
  27. Manach C, Texier O, Morand C, Crespy V, Regerat F, Dcrnigne C, Remesy C. Quercetin is recovered in human plasma as conjugated derivatives which retain antioxidant properties. FASEB Lett. 423: 331-336 (1998)
  28. Manach C, Morand C, Crespy V, Demigne C, Texier O, Regerat F, Remesy C. Comparison of the bioavailability of quercetin and catechin in rats. Free Rad. Biol. Med. 27: 1259-1266 (1999) https://doi.org/10.1016/S0891-5849(99)00159-8
  29. Hallman PC, de Vries JH, van Leeuwen SD, Mengelers MJ, Katan MB. Absorption of dietary quercetin glycosides and quercetin in healthy isolectomy volunteers. Am. J. Clin. Nutr. 62: 1276-1282 (1995)
  30. Hallman PCH, van Trijp JMP, Mengelers MJB, de Vries JHM, Katan MB. Bioavailability of the dietary antioxidant flavonol quercetin in man. Cancer Lett. 114: 139-140 (1997) https://doi.org/10.1016/S0304-3835(97)04644-2
  31. Hertog MGL, Katan MB. Quercetin in foods, cardiovascular disease, and cancer. pp. 199-219. In: Flavonoids in Health and Disease. Rice-Evans C and Parker L (ed). Marcel Dekker, Inc., New York, USA (1998)
  32. Sesink ALA, O'Leary KA, Hollman PCH. Quercetin glucuronides but not glucosides are present in human plasma after consumption of quercetin-3-glucoside or quercetin-4'-glucoside. J. Nutr. 131: 1938-1941 (2001)
  33. Meng X, Maliakal P, Lu H, Lee MJ, Yang CS. Urinary and plasma levels of resveratrol and quercetin in humans, mice, and rats after injestion of pure compounds and grape juice. J. Agric. Food Chem. 52: 935-942 (2004) https://doi.org/10.1021/jf030582e