Inhibition of human lens aldose reductase by flavonoids, sulindac and indomethacin

Chaudhry, Prem S.; Cabrera, José Luis; Juliani, H. Rodolfo; Varma, Shambhu D.

doi:10.1016/0006-2952(83)90417-3

Cited by 91 publications

(41 citation statements)

References 13 publications

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“…Compared to our finding for indomethacin inhibition of rabbit ALR2 (32.8% inhibition at 100 μmol/l), Chaudhry et al 1983 reported one order higher efficacy (34% inhibition at 10 μmol/l concentration) in relation to human ALR2 isolated from eye lenses. The ALR2 inhibition activities of structurally related derivatives were recorded, namely those of 1-indole butanoic acid with IC 50 values ranging from 7.4 to 37 μmol/l (Sun et al 2003), cyano(2-oxo-2,3-dihydroindole-3-ylidene) acetic acid with IC 50 varying from 0.075 to 5.40 μmol/l (Da Settimo et al 2003) and (3-benzoylindol-1-yl)acetic acid with 38% ALR2 inhibition at 1 μmol/l concentration (Nicolaou and Demopoulos 2003).…”

Section: Aldose Reductase Inhibitioncontrasting

confidence: 51%

Substituted derivatives of indole acetic acid as aldose reductase inhibitors with antioxidant activity: structure-activity relationship

Juskova¹,

Májeková²,

Demopoulos³

et al. 2012

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Abstract. Although multiple biochemical pathways are likely to be responsible for the pathogenesis of diabetic complications, substantial evidence suggests a key role for the polyol pathway and oxidative stress initiated by hyperglycemia. Thus aldose reductase, the first enzyme of the polyol pathway, has been identified as a potential target of pharmacological intervention to prevent diabetic complications. Aldose reductase inhibitors endowed with antioxidant activity would be dually beneficial. The aim of the study was to evaluate the structure-activity relationship of commercially available indole derivatives supported by the molecular modeling of their interaction with the enzyme aldose reductase from the viewpoint of the inhibitory effect on the enzyme and their antioxidant activity. The partially purified aldose reductase was prepared from rabbit eye lenses. In vitro inhibiton of the aldose reductase was determined by a conventional method. Antioxidant action of the compounds was documented in a DPPH test. Marked differences were recorded in the aldose reductase inhibition activities of 1-and 3-indole acetic acid derivatives. The interaction energies of the inhibitor vs. enzyme-NADP + complexes, calculated by computer aided molecular modeling, were in agreement with the higher inhibitory efficacy of 1-indole acetic acid in contrast with 3-indole acetic acid. The more efficient 1-indole acetic acid was proved to create stronger electrostatic interaction with NADP + . However, the order of the antioxidant activities of the compounds studied was not in agreement with that of the inhibitory efficacies.

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Section: Aldose Reductase Inhibitioncontrasting

confidence: 51%

Substituted derivatives of indole acetic acid as aldose reductase inhibitors with antioxidant activity: structure-activity relationship

Juskova¹,

Májeková²,

Demopoulos³

et al. 2012

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“…Inhibition of histamine release from mast cells and basophils (Fox et al;Bronner and Landry, 1985), also contributes to quercetin's anti-inflammatory activity. Quercetin also blocks aldose reductase, an enzyme which catalyzes the conversion of glucose to sorbitol, which has been linked to nerve, eye and kidney damage in diabetes mellitus (Chaudry et al;1983).…”

Section: Discussionmentioning

confidence: 99%

Protective effect of quercetin on the morphology of pancreatic β-cells of streptozotocin-treated diabetic rats

Adewole

Caxton-Martins²,

Ojewole³

2007

Afr. J. Trad. Compl. Alt. Med.

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This study was undertaken to investigate the protective effects of quercetin (QCT) on the morphology of pancreatic β-cells against diabetes mellitus and oxidative stress experimentally-induced by streptozotocin (STZ) treatment in Wistar rats. Fifty male and female Wistar rats (200-250 g) were randomly divided into three experimental groups (i. e., control, STZ-treated, and STZ + Quercetin-treated groups). Diabetes was induced in the diabetic groups (B and C) of animals, by a single intraperitoneal injection of STZ (75 mg/kg), while each of the rats in the 'control' group received equal volume of citrate buffer (pH 6.3) solution intraperitoneally. In group C rats, quercetin (QCT, 25 mg/kg/day i. p.) was injected daily for 3 days prior to STZ treatment, and QCT administration continued until the end of the study period (30 days). Diabetes mellitus was confirmed by using Bayer's Glucometer Elite ® and compatible blood glucose test strips. The rats were sacrificed serially until the end of the study period (after 30 days). The pancreases of the sacrificed rats were excised and randomly processed for histological staining and biochemical assays for antioxidant enzymes [such as glutathione peroxidase (GSHPx), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA) and serum nitric oxide (NO)]. In the diabetic state, pancreatic β-cells of STZ-treated group B rats histologically demonstrated an early chromatin aggregation, cytoplasmic vesiculation in the central β-cells, nuclear shrinkage, and lysis of β-cells with distortion of granules. The morphology of QCT-treated rats' pancreases showed viable cellularity with distinct β-cell mass. STZ treatment significantly decreased (p<0.05) GSHPx, SOD, CAT and pancreatic insulin content. However, STZ treatment increased blood glucose concentrations, MDA and serum NO. The QCT-treated group of animals showed a significant decrease (p<0.05) in elevated blood glucose, MDA and NO. Furthermore, QCT treatment significantly increased (p<0.05) antioxidant enzymes' activities, as well as pancreatic insulin contents. Quercetin (QCT) treatment protected and preserved pancreatic β-cell architecture and integrity. In conclusion, the findings of the present experimental animal study indicate that QCT treatment has beneficial effects on pancreatic tissues subjected to STZ-induced oxidative stress by directly quenching lipid peroxides and indirectly enhancing production of endogenous antioxidants.

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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%

“…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 .…”

Section: Introductionmentioning

confidence: 99%

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 human lens aldose reductase by flavonoids, sulindac and indomethacin

Cited by 91 publications

References 13 publications

Substituted derivatives of indole acetic acid as aldose reductase inhibitors with antioxidant activity: structure-activity relationship

Substituted derivatives of indole acetic acid as aldose reductase inhibitors with antioxidant activity: structure-activity relationship

Protective effect of quercetin on the morphology of pancreatic β-cells of streptozotocin-treated diabetic rats

Inhibitory action on aldose reductase by soybean flavonoids

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Inhibition of human lens aldose reductase by flavonoids, sulindac and indomethacin

Cited by 91 publications

References 13 publications

Substituted derivatives of indole acetic acid as aldose reductase inhibitors with antioxidant activity: structure-activity relationship

Substituted derivatives of indole acetic acid as aldose reductase inhibitors with antioxidant activity: structure-activity relationship

Protective effect of quercetin on the morphology of pancreatic β-cells of streptozotocin-treated diabetic rats

Inhibitory action on aldose reductase by soybean flavonoids

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Substituted derivatives of indole acetic acid as aldose reductase inhibitors with antioxidant activity: structure-activity relationship

Substituted derivatives of indole acetic acid as aldose reductase inhibitors with antioxidant activity: structure-activity relationship