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Xanthine and Aldehyde Oxidase Inhibitory Activities, and Antihyperuricemic Effects of Fermented Smilax china L. Leaf Extracts and Fractions

발효 청미래덩굴잎 용매 추출물 및 분획물의 xanthine 및 aldehyde oxidase 저해활성과 항고요산혈증 효과

  • Lee, Sang-Il (Dept. of Food, Nutrition and Cookery, Keimyung College) ;
  • Lee, Ye-Kyung (Center for Nutraceutical and Pharmaceutical Materials, Myongji University) ;
  • Kim, Soon-Dong (Center for Nutraceutical and Pharmaceutical Materials, Myongji University) ;
  • Cheng, Jinhua (Center for Nutraceutical and Pharmaceutical Materials, Myongji University) ;
  • Yang, Seung Hwan (Center for Nutraceutical and Pharmaceutical Materials, Myongji University) ;
  • Suh, Joo-Won (Center for Nutraceutical and Pharmaceutical Materials, Myongji University)
  • Received : 2013.08.01
  • Accepted : 2013.09.16
  • Published : 2014.03.31

Abstract

To evaluate the inhibitory effect of xanthine oxidase (XO) and aldehyde oxidase (AO), and antihyperuricemic effect by Aspergillus oryzae fermented Smilax china L. leaf extracts and fractions, we observed extracted yield by each solvent, the content of total polyphenol and total flavonoid (TF), the activities of XO and AO, and serum uric acid level. Extracted yield (g/kg) by 80% ethanol (EtOH) was 13.56, those of n-hexane, dichloromethane (DICM), ethylacetate (EtOAc) and n-butanol fraction (BuOH) were 1.35-3.33. Furthermore, total polyphenol content (mg/g-extract) of EtOAc fraction, BuOH fraction, DICM fraction and EtOH fraction is 478.07-501.26, 259.49-289.02, 165.03-232.27, 134.02-196.54, respectively. Those of fermented EtOAc and DICM fraction was 4.85 and 40.74% higher than that of non-fermented fraction, respectively, while the other fermented fractions were lower than those of non-fermented fractions. And total flavonoid content (mg/g-extract) of EtOAc fraction was higher than those of other fractions. Additionally, TF of fermented EtOAc and BuOH fraction is 10.56 and 60.17% higher, than that of fermented fraction, respectively, although those of the other fermented fractions was lower than that of non-fermented fractions. On the other hand, XO inhibitory activities of all fermented fractions was significantly higher than that of all non-fermented fraction, while those of fermented EtOAc (75.02%) and BuOH fraction (65.59%) was markedly higher than that of non-fermented fraction (39.42 and 5.34%), respectively. In addition, AO inhibitory activities of DICM and EtOAc fraction was 81.82 and 77.93% higher, respectively, than those of the other fractions, and those of fermented fractions as with XO were significantly higher than that of non-fermented fractions. Meanwhile, serum uric acid level (SU) of hyperuricemic control mice (HC, 6.98 mg/dL) was 1.83 folds higher than that of normal control (NC, 3.82 mg/dL). Furthermore, SU in the group treated with EtOAc fraction decreased in a dose dependent manner compared with the allopurinol control group, although those of fermented fractions were significantly lower than those of non-fermented fractions. This study suggests that fermented Smilax china L. leaf extracts may regulate the XO and AO inhibitory activities and antihyperuricemic effect due to aglycone components from glycoside form flavonoids by fermentation of A. oryzae.

Aspergillus oryzae로 발효시킨 청미래덩굴잎 용매추출분획물의 xanthine oxidase (XO) 및 aldehyde oxidase (AO) 저해활성과 항고요산혈증에 미치는 영향을 조사하였다. 용매별 추출수율(g/kg)은 80% ethanol (EtOH)은 13.56이었으며, n-hexane, dichloromethane (DICM), ethylacetate (EtOAc) 및 n-butanol fraction (BuOH)은 1.35-3.33 범위였다. Total polyphenol 함량(mg/g-extract)은 EtOAc fraction 478.07-501.26, BuOH fraction 259.49-289.02, DICM fraction 165.03-232.27, EtOH fraction 134.02-196.54이었으며 EtOAc 및 DICM fraction에서는 발효시킨 경우가 비발효에 비하여 각각 4.85 및 40.74%가 높았으나 그 외 모든 fraction에서는 발효시킨 경우가 낮았다. 총 flavonoid 함량은 EtOAc fraction이 여타 fraction에 비하여 높았다. EtOAc 및 BuOH fraction의 TF 함량은 발효시킨 경우가 비 발효에 비하여 각각 10.56% 및 60.17%가 높았으나 여타 fraction들에서는 발효시킨 경우가 낮았다. XO 저해활성은 모든 분획물에서 발효시킨 경우가 비발효에 비하여 현저하게 높았으며 EtOAc 및 BuOH fraction의 경우 발효시킨 경우는 각각 75.02 및 65.59%로 비발효 경우 39.42 및 5.34% 보다 현저하게 높았다. AO 저해활성은 DICM과 EtOAc fraction에서 각각 81.82 및 77.93%로 여타 fraction들에 비하여 높았으며 XO의 경우와 마찬가지로 발효시킨 경우가 비발효에 비하여 현저하게 높았다. 고요산혈증 mouse의 혈중 요산(SU) 함량에 미치는 영향을 조사한 결과, 고요산혈증 대조군의 SU 함량은 6.98 mg/dL로 정상대조군 (NC)의 3.82 mg/dL에 비하여 1.83배가 높았으나, EtOAc fraction은 투여량에 의존적으로 SU의 함량이 감소하였으며, 발효시킨 경우가 비발효에 비하여 유의적인 감소를 보였다. 이상의 결과, A. oryzae와 청미래덩굴잎의 발효과정을 통해, glycoside형태의 flavonoid를 aglycone화하여 비발효에 비해 높은 XO 및 AO 저해활성과 함께 항고요산혈증 효과를 나타내는 것으로 사료된다.

Keywords

References

  1. Al-Salmy HS (2001) Individual variation in hepatic aldehyde oxidase activity. IUBMB Life 51, 249-53. https://doi.org/10.1080/152165401753311799
  2. Beedham C (1987) Molybdenum hydroxylases: biological distribution and substrate- inhibitor specificity. Prog Med Chem 24, 85-121. https://doi.org/10.1016/S0079-6468(08)70420-X
  3. Bennick A (2002) Interaction of plant polyphenols with salivary proteins. Crit Rev Oral Biol Med 13, 184-96. https://doi.org/10.1177/154411130201300208
  4. Bomalaski JS and Clark MA (2004) Serum uric acid-lowering therapies: where are we heading in management of hyperuricemia and the potential role of uricase. Curr Rheumatol Rep 6, 240-7. https://doi.org/10.1007/s11926-004-0075-3
  5. Cha BC and Lee EH (2007) Antioxidant activities of flavonoids from the leaves of Smilax china Linne. Kor J Pharmacogn 38, 31-6.
  6. Chena L, Yina H, Lanb Z, Maa S, Zhanga C, Yanga Z et al. (2011) Antihyperuricemic and nephroprotective effects of Smilax china L. J Ethnopharmacol 135, 399-405. https://doi.org/10.1016/j.jep.2011.03.033
  7. Clarke SE, Harrell AW, and Chenery RJ (1995) Role of aldehyde oxidase in the in vitro conversion of famciclovir to penciclovir in human liver. Drug Metab Dispos 23, 251-4.
  8. Conklin D, Prough R, and Bhatanagar A (2007) Aldehyde metabolism in the cardiovascular system. Mol Biosyst 3, 136-50. https://doi.org/10.1039/b612702a
  9. Dawson J and Walters M (2006) Uric acid and xanthine oxidase: future therapeutic targets in the prevention of cardiovascular disease? Br J Clin Pharmacol 62, 633-44. https://doi.org/10.1111/j.1365-2125.2006.02785.x
  10. Duan X and Ling F (2008) Is uric acid itself a player or a bystander in the pathophysiology of chronic heart failure? Med Hypotheses 70, 578-81. https://doi.org/10.1016/j.mehy.2007.06.018
  11. Garattini E and Terao M (2011) Increasing recognition of the importance of aldehyde oxidase in drug development and discovery. Drug Metab Rev 43, 374-86. https://doi.org/10.3109/03602532.2011.560606
  12. Guo J, Qian F, Li J, Xu Q, and Chen T (2007) Identification of a new metabolite of astilbin, 3-O-methylastilbin, and its Immunosuppressive activity against contact dermatitis. Clinical Chemistry 53, 465-71. https://doi.org/10.1373/clinchem.2006.077297
  13. Hamzeh-Mivehroud M, Rahmani S, Rashidi MR, Hosseinpour Feizi MA, and Dastmalchi S (2013) Structure-based investigation of rat aldehyde oxidase inhibition by flavonoids. Xenobiotica 43, 661-70. https://doi.org/10.3109/00498254.2012.755228
  14. Hill JO, Lin D, Yakubu F, and Peter JC (1992) Development of dietary obesity in rats: influence of amount andcomposition of dietary fat. Int J Obes Relat Matab Disord 16, 321-33.
  15. Hirao Y, Kitamura S, and Tatsumi, K (1994) Epoxide reductase activity of mammalian liver cytosols and aldehyde oxidase. Carcinogenesis 15, 739-43. https://doi.org/10.1093/carcin/15.4.739
  16. Hokazono H, Toshiro Omori T, and Kazuhisa Ono K (2010) Antihyperuricemic effect of fermented barley extract is associated with increased urinary uric acid excretion. Food Sci Technol Res 16, 295-304. https://doi.org/10.3136/fstr.16.295
  17. Horiuchi H, Ota M, Nishimura S, Kaneko H, Kasahara Y, Ohta T et al. (2000) Allopurinol induces renal toxicity by impairing pyrimidine metabolism in mice. Life Sci 66, 2051-70. https://doi.org/10.1016/S0024-3205(00)00532-4
  18. Huang DY and Ichikawa Y (1994). Two different enzymes are primarily responsible for retinoic acid synthesis in rabbit liver cytosol. Biochem Biophys Res Commun 205, 1278-83. https://doi.org/10.1006/bbrc.1994.2803
  19. Jordan CGM, Rashidi MR, Laljee H, Clarke SE, Brown JE, and Beedham C (1999) Aldehyde oxidase-catalyzed oxidation of methotrexate in the liver of guinea- pig, rabbit and man. J Pharm Pharmacol 51, 411-8. https://doi.org/10.1211/0022357991772619
  20. Kawashima K, Hosoi K, Naruke T, Shiba T, Kitamura M, and Watabe T (1999) Aldehyde oxidasedependent marked species difference in hepatic metabolism of the sedative-hypnotic, zeleplon, between monkeys and rats. Drug Metab Dispos 27, 422-8.
  21. Kitamura S, Nakatani K, Sugihara K, and Ohta S (1999) Strain differences of the ability to hydroxylate methotrexate in rats. Comp Biochem Physiol 122, 331-6. https://doi.org/10.1016/S1095-6433(99)00014-8
  22. Kong LD, Cai Y, Huang WW, Christopher HK, Cheng CHK, and Tan RX (2000) Inhibition of xanthine oxidase by some Chinese medicinal plants used to treat gout. J Ethnopharmacol 73, 199-207. https://doi.org/10.1016/S0378-8741(00)00305-6
  23. Kong LD, Zhou J, Wen YL, Li JM, and Cheng CHK (2002) Aesculin possesses potent hypouricemic action in rodents but is devoid of xanthine oxidase/dehydrogenase inhibitory activity. Planta Med 68, 175-8. https://doi.org/10.1055/s-2002-20262
  24. Kramer HM and Curhan G (2002) The association between gout and nephrolithiasis: the National Health and Nutrition Examination Survey III 1988-1994. Am J Kidney Dis 40, 37-42. https://doi.org/10.1053/ajkd.2002.33911
  25. Kundu TK, Hille R, Velayutham M, and Zweier JL (2007) Characterization of superoxide production from aldehyde oxidase: an important source of oxidants in biological tissues. Arch Biochem Biophys 460, 113-21. https://doi.org/10.1016/j.abb.2006.12.032
  26. Lee SI, Lee YK, Kim SD, Kang YH, and Suh JW (2012) Antioxidative activity of Smilax china L. leaf teas fermented by different strains. Korean J Food Nutr 25, 807-19. https://doi.org/10.9799/ksfan.2012.25.4.807
  27. Lesschaeve I and Noble AC (2005) Polyphenols: factors influencing their sensory properties and their effects on food and beverage preferences. Am J Clin Nutr 81, 330S-5S. https://doi.org/10.1093/ajcn/81.1.330S
  28. Leyva F, Anker SD, Swan JW, Godsland IF, Wingrove CS, Chua TP et al. (1997) Serum uric acid as an index of impaired oxidative metabolism in chronic heart failure. Eur Heart J 18, 858-65. https://doi.org/10.1093/oxfordjournals.eurheartj.a015352
  29. Maia L and Mira L (2002) Xanthine oxidase and aldehyde oxidase: A simple procedure for the simultaneous purification from rat liver. Arch Biochem Biophys 400, 48-53. https://doi.org/10.1006/abbi.2002.2781
  30. McCrystal M, Evans B, Harvey V, Thompson P, Porter D, and Baguley B (1999) Phase 1 study of the cytotoxic agent N-w2-(dimethylamino) ethylxacridine-4- carboxamide. Cancer Chemother Pharmacol 44, 39-44. https://doi.org/10.1007/s002800050942
  31. Meda A, Lamien CE, Romito M, Millogo J, and Nacoulma OG (2005) Determination of the total phenolic, flavonoid and proline contents in burkina fasan honey, as well as their radical scavenging activity. Food Chem 91, 571-7. https://doi.org/10.1016/j.foodchem.2004.10.006
  32. Mercader J, Ribot J, Murano I, Felipe F, Cinti S, Bonet ML et al. (2006). Remodeling of white adipose tissue after retinoic acid administration in mice. Endocrinology 147, 5325-32. https://doi.org/10.1210/en.2006-0760
  33. Minussi RC, Rossi M, Bologna L, Cordi L, Rotilio D, Pastore GM et al. (2003) Phenolic compounds and total antioxidant potential of commercial wines. Food Chem 82, 409-16. https://doi.org/10.1016/S0308-8146(02)00590-3
  34. Mira L, Maia L, Barreira L, and Manso CF (1995) Evidence for free radical generation due to NADH oxidation by aldehyde oxidase during ethanol metabolism. Arch Biochem Biophys 318, 53-8. https://doi.org/10.1006/abbi.1995.1203
  35. Mo SF, Zhou F, Lv YZ, Hu QH, Zhang DM, and Kong LD (2007) Hypouricemic action of selected flavonoids in mice, structure-activity relationships. Biol Pharm Bull 30, 1551-6. https://doi.org/10.1248/bpb.30.1551
  36. Nagao A, Seki M, and Kobayashi H (1999) Inhibition of xanthine oxidase by flavonoids. Biosci Biotechnol Biochem 63, 1787-90. https://doi.org/10.1271/bbb.63.1787
  37. Parks DA and Granger DN (1986) Xanthine oxidase: Biochemistry, distribution and physiology. Acta Physiol Scand Suppl 548, 87-99.
  38. Pryde DC, Dalvie D, Hu Q, Jones P, Obach RS, and Tran TD (2010). Aldehyde oxidase: an enzyme of emerging importance in drug discovery. J Med Chem 53, 8441-60. https://doi.org/10.1021/jm100888d
  39. Rajagopalan KV, Fridovich I, and Handler P (1962) Hepatic aldehyde oxidase. . Purification and properties. J Biol Chem 237, 922-8.
  40. Rott KT and Agudelo CA (2003) Gout. J Am Med Assoc 289, 2857-60. https://doi.org/10.1001/jama.289.21.2857
  41. Schlesinger N (2004) Management of acute and chronic gouty arthritis: present state-of-the-art. Drugs 64, 2399-416. https://doi.org/10.2165/00003495-200464210-00003
  42. Shao B, Guo HZ, Gui YJ, Ye M, Han J, and Guo DA (2007) Steroidal saponins from Smilax china L. and their anti-inflammatory activities. Phytochem 68, 623-30. https://doi.org/10.1016/j.phytochem.2006.10.026
  43. Shaw S and Jayatilleke E (1990) The role of aldehyde oxidase in ethanolinduced hepatic lipid peroxidation in the rat. Biochem J 268, 579-83.
  44. Shekarriz B and Stoller ML (2002) Uric acid nephrolithiasis: current concepts and controversies. J Urol 168, 1307-14. https://doi.org/10.1016/S0022-5347(05)64439-4
  45. Shi M, Yang Y, Wang Q, Zhang Y, Wang Y, and Zhang Z (2012) Production of total polyphenol from fermented soybean curd residue by Lentinus edodes. Int J Food Sci Technol 47, 1215-21. https://doi.org/10.1111/j.1365-2621.2012.02961.x
  46. Shu XS, Gao ZH, and Yang XL (2006) Anti-inflammatory and antinociceptive activities of Smilax china L. aqueous extract. J Ethnopharmacol 103, 327-32. https://doi.org/10.1016/j.jep.2005.08.004
  47. Stirpe F and Della Corte E (1969) The regulation of rat liver xanthine oxidase. Conversion in vitro of the enzyme activity from dehydrogenase (type D) to oxidase (type O). J Biol Chem 244, 3855-63.
  48. Sugihara K, Kitamura S, and Tatsumi K (1996) Involvement of mammalian liver cytosols and aldehyde oxidase in reductive metabolism of zonisamide. Drug Metab Dispos 24, 199-202.
  49. Tayama Y, Sugihara K, Sanoh S, Miyake K, Morita S, Kitamura S et al. (2011) Effect of tea beverages on aldehyde oxidase activity. Drug Meta Pharmacokinet 26, 94-101. https://doi.org/10.2133/dmpk.DMPK-10-NT-078
  50. Weigert J, Neumeier M, Bauer S, Mages W, Schnitzbauer AA, Obed A et al. (2008) Small-interference RNA-mediated knock-down of aldehyde oxidase 1 in 3T3-L1 cells impairs adipogenesis and adiponectin release. FEBS Lett 582, 2965-72. https://doi.org/10.1016/j.febslet.2008.07.034
  51. Wortmann RL (2002) Gout and hyperuricemia. Curr Opin Rheumatol 14, 2281-6.
  52. Wu LS, Wang XJ, Wang H, Yang HW, Jia AQ, and Ding Q (2010) Cytotoxic polyphenols against breast tumor cell in Smilax china L. J Ethnopharmacol 130, 460-4. https://doi.org/10.1016/j.jep.2010.05.032
  53. Yale SH, Yale ES, and Mann DS (1996) Fever, rash and angioedema after a course of allopurinol. Hosp Pract 31, 92-4.

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