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Flavonoids from the leaves of Thuja orientalis inhibit the aldose reductase and the formation of advanced glycation endproducts

Abstract

The purpose of this study is to evaluate the active properties of Thuja orientalis leaves for the treatment of diabetic complications. The ethyl acetate fraction showed a significantly higher inhibition both of recombinant human aldose reductase (rhALR2) inhibitory activity and advanced glycation endproducts (AGEs). The detected antioxidants (compounds 1–4) by online-HPLC-ABTS+ method and other three compounds were isolated using preparative RP-HPLC and Sephadex LH-20 column chromatography. Among the seven compounds, compound 4 (quercitrin) which was isolated from ethyl acetate fraction, was found to show inhibition for both forms of rhALR2 and AGEs. This compound also inhibited oxidative stress which was measured by Photochem® apparatus. In conclusion, the ethyl acetate fraction from T. orientalis demonstrated antioxidant activity as well as inhibitory effects on rhALR2 and AGEs. Quercitrin was shown to be the active compound and hence could be offered as an active material of standardization for the development of natural products for food or medicines.

Abbreviations

ABTS+ :

2,2′-azinobis-(3-ethylbenzothiazolidine-6-sulfonate

AGEs:

advanced glycation endproducts

BSA:

bovine serum albumin; DAD, diode array detection

HPLC:

high performance liquid chromatography

rhALR2:

recombinant human aldose reductase

ROS:

reactive oxygen species

References

  • Ahmed N (2005) Advanced glycation endproducts role in pathology of diabetic complications. Diabetes Res Clin Pract 67, 3–21.

    Article  CAS  Google Scholar 

  • Apati P, Szentmihalyi K, Kristo ST, Papp I, Vinkler P, Szoke E, and Kery A (2003) Herbal remedies of Solidago correlation of phytochemical characteristics and antioxidative properties. J Pharm Biomed Anal 32, 1045–1053.

    Article  CAS  Google Scholar 

  • Brownlee M (2001) Biochemistry and molecular cell biology of diabetic complications. Nature 414, 813–820.

    Article  CAS  Google Scholar 

  • Carper DA, Wistow G, Nishimura C, Graham C, Watanabe K, Fujii Y, Hayashi H, and Hayaishi O (1989) A superfamily of NADPH-dependent reductases in eukaryotes and prokaryotes. Exp Eye Res 49, 377–388.

    Article  CAS  Google Scholar 

  • Chizzola R, Hochsteiner W, and Hajek S (2004) GC analysis of essential oils in the rumen fluid after incubation of Thuja orientalis twigs in the Rusitec system. Res Vet Sci 76, 77–82.

    Article  CAS  Google Scholar 

  • Dunlop M (2000) Aldose reductase and the role of the polyol pathway in diabetic nephropathy. Kidney Int Suppl 77, S3–12.

    Article  Google Scholar 

  • Fernandez M, Caballero J, Helguera AM, Castro EA, and Gonzalez MP (2005) Quantitative structure-activity relationship to predict differential inhibition of aldose reductase by flavonoid compounds. Bioorg Med Chem 13, 3269–3277.

    Article  CAS  Google Scholar 

  • Frank RN, Keirn RJ, Kennedy A, and Frank KW (1983) Galactose-induced retinal capillary basement membrane thickening: prevention by Sorbinil. Invest Ophthalmol Vis Sci 24, 1519–1524.

    CAS  Google Scholar 

  • Jung SH, Kang SS, Shin KH, and Kim YS (2004) Inhibitory effects of naturally occurring flavonoids on rat lens aldose reductase. Nat Prod Sci 10, 35–39.

    CAS  Google Scholar 

  • Jung SH, Lee JM, Lee HJ, Kim CY, Lee EH, and Um BH (2007) Aldose reductase and advanced glycation endproducts inhibitory effect of Phyllostachys nigra. Biol Pharm Bull 30, 1569–1572.

    Article  CAS  Google Scholar 

  • Koleva, II, Niederlander HA, and van Been TA (2000) An on-line HPLC method for detection of radical scavenging compounds in complex mixtures. Anal Chem 72, 2323–2328.

    Article  CAS  Google Scholar 

  • Koleva, II, Niederlander HA, and van Beek TA (2001) Application of ABTS radical cation for selective on-line detection of radical scavengers in HPLC eluates. Anal Chem 73, 3373–3381.

    Article  CAS  Google Scholar 

  • Lou H, Yuan H, Yamazaki Y, Sasaki T, and Oka S (2001) Alkaloids and flavonoids from peanut skins. Planta Med 67, 345–349.

    Article  CAS  Google Scholar 

  • Matsuda H, Morikawa T, Toguchida I, and Yoshikawa M (2002) Structural requirements of flavonoids and related compounds for aldose reductase inhibitory activity. Chem Pharm Bull (Tokyo) 50, 788–795.

    Article  CAS  Google Scholar 

  • Matsuda H, Wang T, Managi H, and Yoshikawa M (2003) Structural requirements of flavonoids for inhibition of protein glycation and radical scavenging activities. Bioorg Med Chem 11, 5317–5323.

    Article  CAS  Google Scholar 

  • Morimitsu Y, Yoshida K, Esaki S, and Hirota A (1995) Protein glycation inhibitors from thyme (Thymus vulgaris). Biosci Biotechnol Biochem 59, 2018–2021.

    Article  CAS  Google Scholar 

  • Niederlander HA, van Beek TA, Bartasiute A, and Koleva, II (2008) Antioxidant activity assays on-line with liquid chromatography. J Chromatogr A 1210, 121–134.

    Article  Google Scholar 

  • Nishikawa T, Edelstein D, and Brownlee M (2000) The missing link: a single unifying mechanism for diabetic complications. Kidney Int Suppl 77, S26–30.

    Article  Google Scholar 

  • Pelter A, Warren R, Hameed N, Khan NU, Ilyas M, and Rahman W (1970) Biflavonyl pigments from Thuja orientalis (Cupressaceae). Phytochemistry 9, 1897–1898.

    Article  CAS  Google Scholar 

  • Robison WG, Jr., Nagata M, Laver N, Hohman TC, and Kinoshita JH (1989) Diabetic-like retinopathy in rats prevented with an aldose reductase inhibitor. Invest Ophthalmol Vis Sci 30, 2285–2292.

    Google Scholar 

  • Rosen P, Nawroth PP, King G, Moller W, Tritschler HJ, and Packer L (2001) The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCOMCBN, the American Diabetes Association and the German Diabetes Society. Diabetes Metab Res Rev 17, 189–212.

    Article  CAS  Google Scholar 

  • Sato S and Kador PF (1990) Inhibition of aldehyde reductase by aldose reductase inhibitors. Biochem Pharmacol 40, 1033–1042.

    Article  CAS  Google Scholar 

  • Stewart AJ, Mullen W, and Crozier A (2005) On-line highperformance liquid chromatography analysis of the antioxidant activity of phenolic compounds in green and black tea. Mol Nutr Food Res 49, 52–60.

    Article  CAS  Google Scholar 

  • Tomlinson DR, Stevens EJ, and Diemel LT (1994) Aldose reductase inhibitors and their potential for the treatment of diabetic complications. Trends Pharmacol Sci 15, 293–297.

    Article  CAS  Google Scholar 

  • Wu JH, Huang CY, Tung YT, and Chang ST (2008) Online RP-HPLC-DPPH screening method for detection of radical-scavenging phytochemicals from flowers of Acacia confusa. J Agric Food Chem 56, 328–332.

    Article  CAS  Google Scholar 

  • Young RJ, Ewing DJ, and Clarke BF (1983) A controlled trial of sorbinil, an aldose reductase inhibitor, in chronic painful diabetic neuropathy. Diabetes 32, 938–942.

    Article  CAS  Google Scholar 

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Correspondence to Sang Hoon Jung.

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Lee, E.H., Song, DG., Lee, J.Y. et al. Flavonoids from the leaves of Thuja orientalis inhibit the aldose reductase and the formation of advanced glycation endproducts. J. Korean Soc. Appl. Biol. Chem. 52, 448–455 (2009). https://doi.org/10.3839/jksabc.2009.078

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  • DOI: https://doi.org/10.3839/jksabc.2009.078

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