Inhibition of lens aldose reductase by flavonoids—Their possible role in the prevention of diabetic cataracts

Varma, Shambhu D.; Kinoshita, Jin H.

doi:10.1016/0006-2952(76)90457-3

Cited by 194 publications

(83 citation statements)

References 14 publications

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“…Since the mid.-1970's, several studies on the inhibition of aldose reductase by flavonoids have been reported. [14][15][16] However, their structure-activity relationships were not discussed satisfactorily because of the limited number of compounds. In the present study, 94 flavonoids and stilbenes were examined to clarify the further structural requirements of flavonoids for aldose reductase inhibitory activity.…”

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confidence: 99%

Structural Requirements of Flavonoids and Related Compounds for Aldose Reductase Inhibitory Activity.

et al. 2002

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The methanolic extracts of several natural medicines and medicinal foodstuffs were found to show an inhibitory effect on rat lens aldose reductase. In most cases, flavonoids were isolated as the active constituents by bioassay-guided separation, and among them, quercitrin (IC 50 ‫51.0؍‬ m mM), guaijaverin (0.18 m mM), and desmanthin-1 (0.082 m mM) exhibited potent inhibitory activity. Desmanthin-1 showed the most potent activity, which was equivalent to that of a commercial synthetic aldose reductase inhibitor, epalrestat (0.072 m mM). In order to clarify the structural requirements of flavonoids for aldose reductase inhibitory activity, various flavonoids and related compounds were examined. The results suggested the following structural requirements of flavonoid: 1) the flavones and flavonols having the 7-hydroxyl and/or catechol moiety at the B ring (the 3,4-dihydroxyl moiety) exhibit the strong activity; 2) the 5-hydroxyl moiety does not affect the activity; 3) the 3-hydroxyl and 7-O-glucosyl moieties reduce the activity; 4) the 2-3 double bond enhances the activity; 5) the flavones and flavonols having the catechol moiety at the B ring exhibit stronger activity than those having the pyrogallol moiety (the 3,4,5-trihydroxyl moiety).

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confidence: 99%

Structural Requirements of Flavonoids and Related Compounds for Aldose Reductase Inhibitory Activity.

et al. 2002

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“…Also, the type of inhibition by these flavonoids is noncompetitive, a factor preferable in therapeutic use over competitive inhibitors. 27,28) Furthermore, previous studies indicate that common feature of aldose reductase inhibitors is a hydrophobic region attached to an acid group. The flavonoids meet these requirements.…”

Section: Chemicalsmentioning

confidence: 99%

Aldose Reductase Inhibitory Compounds from Glycyrrhiza uralensis

Lee

Kim

Jung

et al. 2010

Biological & Pharmaceutical Bulletin

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We evaluated the inhibitory effects of components from the root of Glycyrrhiza uralensis (G. uralensis) on aldose reductase (AR) and sorbitol formation in rat lenses with high levels of glucose as part of our ongoing search of natural sources for therapeutic and preventive agents for diabetic complications. In order to identify the bioactive components of G. uralensis, 5 prenylated flavonoids (semilicoisoflavone B, 7-O-methylluteone, dehydroglyasperin C, dehydroglyasperin D, and isoangustone A), three flavonoids (liquiritigenin, isoliquiritigenin, and licochalcone A), and two triterpenoids (glycyrrhizin and glycyrrhetinic acid) were isolated; their chemical structures were then elucidated on the basis of spectroscopic evidence and comparison with published data. The anti-diabetic complication activities of 10 G. uralensis-derived components were investigated via inhibitory assays using rat lens AR (rAR) and human recombinant AR (rhAR). From the 10 isolated compounds, semilicoisoflavone B showed the most potent inhibition, with the IC 50 values of rAR and rhAR at 1.8 and 10.6 m mM, respectively. In the kinetic analyses using Lineweaver-Burk plots of 1/velocity and 1/concentration of substrate, semilicoisoflavone B showed noncompetitive inhibition against rhAR. The results clearly indicated that the presence of a g g,g g-dimethylchromene ring is partly responsible for the AR inhibitory activity of isoprenoid-type flavonoids. Further, semilicoisoflavone B inhibited sorbitol formation of rat lens incubated with a high concentration of glucose, indicating that this compound may be effective for preventing osmotic stress in hyperglycemia.

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“…Flavonoids that are pres ent in higher plants, mainly legu mi nous, have aroused in ter est be cause of their in hib i tory ac tion on aldose reductase 1,2,3 . Aldose reductase ca tal y ses the re duc tion of glu cose and galactose, pro duc ing sorbitol and dulcitol re spec tively, us ing NADH as a co-factor 4 .…”

Section: Introductionmentioning

confidence: 99%

“…The ex ces sive pres ence of sorbitol in di a betic rats and hu mans causes the for ma tion of cat a racts 2,5,6 . A sim i lar result was also ob served by the pres ence of dulcitol in the lenses of rats main tained on a diet rich in galactose 7 .…”

Section: Introductionmentioning

confidence: 99%

“…Aldose reductase ca tal y ses the re duc tion of glu cose and galactose, pro duc ing sorbitol and dulcitol re spec tively, us ing NADH as a co-factor 4 . This en zyme has been found in many an i mal tis sues, such as the ret ina, blood, the cor nea, the sci atic nerve, the liver, kidneys and sperm.The ex ces sive pres ence of sorbitol in di a betic rats and hu mans causes the for ma tion of cat a racts 2,5,6 . A sim i lar result was also ob served by the pres ence of dulcitol in the lenses of rats main tained on a diet rich in galactose 7 .…”

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confidence: 99%

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Inhibitory action on aldose reductase by soybean flavonoids

Oliveira¹,

Nagem²,

Miranda³

et al. 1997

J. Braz. Chem. Soc.

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Os flavonóides kaempherol, genisteína, naringenina, quercetina, morina, rutina, e quercitrina isolados do cultivar de soja UFV-5' foram testados como inibidores de aldose redutase. Os melhores resultados foram obtidos usando morina e quercitrina.The flavonoids kaempherol, genistein, naringenin, quercetin, morin, rutin and quercitrin iso lated from UFV-5'soybean's cultivars were tested as in hib i tors of aldose reductase. The best re sults were ob tained by us ing morin and quercitrin. Key words: flavonoids, soy bean, aldose reductase In tro duc tionFlavonoids that are pres ent in higher plants, mainly legu mi nous, have aroused in ter est be cause of their in hib i tory ac tion on aldose reductase 1,2,3 . Aldose reductase ca tal y ses the re duc tion of glu cose and galactose, pro duc ing sorbitol and dulcitol re spec tively, us ing NADH as a co-factor 4 . This en zyme has been found in many an i mal tis sues, such as the ret ina, blood, the cor nea, the sci atic nerve, the liver, kidneys and sperm.The ex ces sive pres ence of sorbitol in di a betic rats and hu mans causes the for ma tion of cat a racts 2,5,6 . A sim i lar result was also ob served by the pres ence of dulcitol in the lenses of rats main tained on a diet rich in galactose 7 . In the lenses of di a betic rats the con tent of sorbitol may be as high as 50 µmol/g, while in the lenses of galactosemic rats, the level of dulcitol can rise to ap prox i mately 80 µmol/g wet weight tis sue 4 . It has been dem on strated that cat a ract forma tion ceases un der the sys temic ad min is tra tion of aldose reductase in hib i tors 7,8 . In or der to solve this prob lem several com pounds have been tested 6,8,9,10 , be sides flavonoids 1,3 . The pur pose of the pres ent study is to iso late, pu rify and iden tify flavonoidic com pounds of the UFV-5' soy bean's cultivar, as well as to test their in hib i tory ac tion in aldose reductase in vi tro . Ma te rial and MethodsThe flavonoids kaempherol (I), genistein (II), quercetin (III), naringenin (IV), morin (V), rutin (VI) and quercitrin (VIII) were ex tracted from the UFV-5'soybean's cultivar, fol low ing Hardin's tech nique 11 . The sam ple was heated in a bath-water with ace tic acid for 10 min, and then fil tered. The fil trate was treated with HCl 1 N for one hour, and then ex tracted with an hy drous ethyl ether which was evap o rated giv ing a res i due con tain ing flavonoidic com po nents isolated by chro ma tog ra phy.Ar ti cle

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Inhibition of lens aldose reductase by flavonoids—Their possible role in the prevention of diabetic cataracts

Cited by 194 publications

References 14 publications

Structural Requirements of Flavonoids and Related Compounds for Aldose Reductase Inhibitory Activity.

Structural Requirements of Flavonoids and Related Compounds for Aldose Reductase Inhibitory Activity.

Aldose Reductase Inhibitory Compounds from Glycyrrhiza uralensis

Inhibitory action on aldose reductase by soybean flavonoids

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