Structural requirements of flavonoids for inhibition of protein glycation and radical scavenging activities.

To clarify the structural requirements of flavonoids for formation of advanced glycation end-products (AGEs), various flavonoids were examined. The results suggested the following structural requirements of flavonoids for the inhibition of AGEs formation: (1). as the hydroxyl groups at the 3'-, 4'-, 5-, and 7-positions increased in number, the inhibitory activities became stronger; (2). the activities of flavones were stronger than those of corresponding flavonols, flavanones, and isoflavones; (3). methylation or glucosylation of the 4'-hydroxyl group of flavones, flavonols, and flavanones reduced activity; (4). methylation or glycosylation of the 3-hydroxyl group of flavonols tended to increase activity; (5). glycosylation of the 7-hydroxyl group of flavones and isoflavones reduced activity. In addition, various flavonoids with strong AGEs formation inhibitory activity tended to exhibit strong scavenging activity for 1,1-diphenyl-2-picrylhydrazyl and superoxide anion radicals, with several exceptions.

[1]  雅之 吉川,et al.  Salacia属植物のポリフェノール成分:α-グルコシダーゼ及びアルドースレダクターゼ阻害活性成分,Mangiferin,の定量分析 , 2001 .

[2]  N. Sugihara,et al.  The contribution of the pyrogallol moiety to the superoxide radical scavenging activity of flavonoids. , 2002, Biological & pharmaceutical bulletin.

[3]  M. S. Blois,et al.  Antioxidant Determinations by the Use of a Stable Free Radical , 1958, Nature.

[4]  D. T. Kalenda,et al.  Radical scavenging and xanthine oxidase inhibitory activity of phenolic compounds from Bridelia ferruginea stem bark , 2001, The Journal of pharmacy and pharmacology.

[5]  J. McCord.  Superoxide radical: A likely link between reperfusion injury and inflammation , 1986 .

[6]  K. Fukuzawa,et al.  [Biochemical studies of the physiological function of tocopheronolactone. 1]. , 1968, Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan.

[7]  J. Kehrer.  Free radicals as mediators of tissue injury and disease. , 1993, Critical reviews in toxicology.

[8]  Masayuki Yoshikawa,et al.  Structural requirements of flavonoids and related compounds for aldose reductase inhibitory activity. , 2002, Chemical & pharmaceutical bulletin.

[9]  C. Corsaro,et al.  In vitro scavenger activity of some flavonoids and melanins against O2-(.). , 1991, Free radical biology & medicine.

[10]  H. Matsuda,et al.  Antidiabetogenic activity of oleanolic acid glycosides from medicinal foodstuffs. , 2000, BioFactors.

[11]  I. G. Fantus,et al.  Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[12]  H. Shimoda,et al.  Salacia reticulata and its polyphenolic constituents with lipase inhibitory and lipolytic activities have mild antiobesity effects in rats. , 2002, The Journal of nutrition.

[13]  I. Fridovich,et al.  Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). , 1969, The Journal of biological chemistry.

[14]  H. Matsuda,et al.  Synthesis of a Nitrogen Analogue of Salacinol and Its α-Glucosidase Inhibitory Activity , 2001 .

[15]  A. Cerami,et al.  Protein glycation, diabetes, and aging. , 2001, Recent progress in hormone research.

[16]  H. Matsuda,et al.  Absolute stereostructure of potent alpha-glucosidase inhibitor, Salacinol, with unique thiosugar sulfonium sulfate inner salt structure from Salacia reticulata. , 2002, Bioorganic & medicinal chemistry.

[17]  T. Yokozawa,et al.  Protective activity of green tea against free radical- and glucose-mediated protein damage. , 2002, Journal of agricultural and food chemistry.

[18]  H. Lou,et al.  Alkaloids and flavonoids from peanut skins. , 2001, Planta medica.

[19]  M. Brownlee.  Biochemistry and molecular cell biology of diabetic complications , 2001, Nature.

[20]  K. Yoshida,et al.  Protein glycation inhibitors from thyme (Thymus vulgaris). , 1995, Bioscience, biotechnology, and biochemistry.

[21]  T. Yokozawa,et al.  Study on the inhibitory effect of tannins and flavonoids against the 1,1-diphenyl-2 picrylhydrazyl radical. , 1998, Biochemical pharmacology.

[22]  K. Cimanga,et al.  Structure-activity relationship and classification of flavonoids as inhibitors of xanthine oxidase and superoxide scavengers. , 1998, Journal of natural products.

[23]  Y. Sato,et al.  Preparative-scale isolation of four anthocyanin components of black currant (Ribes nigrum L.) fruits. , 2001, Journal of agricultural and food chemistry.

[24]  Y. Kaneda,et al.  Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage , 2000, Nature.

[25]  H. Matsuda,et al.  Medicinal Foodstuffs. XXVI. Inhibitors of Aldose Reductase and New Triterpene and Its Oligoglycoside, Centellasapogenol A and Centellasaponin A, from Centella asiatica (Gotu Kola) , 2001 .

[26]  H. Matsuda,et al.  Antidiabetogenic constituents from several natural medicines , 2002 .

[27]  H. Matsuda,et al.  Antidiabetic principles of natural medicines. V. Aldose reductase inhibitors from Myrcia multiflora DC. (2): Structures of myrciacitrins III, IV, and V. , 2002, Chemical & pharmaceutical bulletin.

[28]  B. Taffe,et al.  Free radicals in tumor promotion , 1986 .

[29]  S. Tsuchiya,et al.  Superoxide production from nonenzymatically glycated protein , 1988, FEBS letters.

[30]  T. Nohara,et al.  DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activity of flavonoids obtained from some medicinal plants. , 2001, Biological & pharmaceutical bulletin.

[31]  Rui M. Rocha,et al.  Structure-antioxidant Activity Relationships of Flavonoids: A Re-examination , 2002, Free radical research.

[32]  H. Matsuda,et al.  Medicinal flowers. VI. Absolute stereostructures of two new flavanone glycosides and a phenylbutanoid glycoside from the flowers of Chrysanthemum indicum L.: their inhibitory activities for rat lens aldose reductase. , 2002, Chemical & pharmaceutical bulletin.

[33]  G. Paolisso,et al.  Oxidative stress and insulin action: is there a relationship? , 1996, Diabetologia.