Aldose reductase inhibitors from the leaves of Myrdaria dubia (H. B. & K.) McVaugh
ABSTRACT Ellagic acid (1) and its two derivatives, 4-O-methylellagic acid (2) and 4-(alpha-rhamnopyranosyl)ellagic acid (3) were isolated as inhibitors of aldose reductase (AR) from Myrciaria dubia (H. B. & K.) McVaugh. Compound 2 was the first isolated from the nature. Compound 3 showed the strongest inhibition against human recombinant AR (HRAR) and rat lens AR (RLAR). Inhibitory activity of compound 3 against HRAR (IC50 value = 4.1 x 10(-8) M) was 60 times more than that of quercetin (2.5 x 10(-6) M). The type of inhibition against HRAR was uncompetitive.
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ABSTRACT: Diabetic complications are attributed to hyperglycaemic condition which is in turn associated with the polyol pathway and advanced glycation end products. Aldose reductase (AR) is the principal enzyme of polyol pathway which plays a vital role in the development of diabetic complications. AR inhibitory activity can be screened by both in vitro and in vivo methods. In vitro assays for AR enzyme are further classified on the basis of the source of enzyme such as rat lens, rat kidney, cataracted human eye lens, bovine eyes and human recombinant AR enzymes, whereas the in vivo model is based on the determination of lens galactitol levels. A number of synthetic AR inhibitors (ARIs) including tolrestat and sorbinil have been developed, but all of these suffer from drawbacks such as poor permeation and safety issues. Therefore, pharmaceutical companies and many researchers have been carrying out research to find new, potent and safe ARIs from natural sources. Thus, many naturally occurring compounds have been reported to have AR inhibitory activity. The present review attempts to highlight phytochemicals and plant extracts with potential AR inhibitory activity. It also summarizes the classes of compounds which have proven AR inhibitory activity. Phytochemicals such as quercetin, kaempferol and ellagic acid are found to be the most promising ARIs. The exhaustive literature presented in this article clearly indicates the role of plant extracts and phytochemicals as potential ARIs. Copyright © 2013 John Wiley & Sons, Ltd.Phytotherapy Research 03/2014; 28(3). DOI:10.1002/ptr.5000
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ABSTRACT: To evaluate the aldose reductase inhibitory (ARI) activity of different fractions of Hybanthus enneaspermus for potential use in diabetic cataract. Total phenol and flavonoid content of different fractions was determined. ARI activity of different fractions in rat lens was investigated in vitro. The results showed significant level of phenolic and flavonoid content in ethyl acetate fraction [total phenol (212.15±0.79 mg/g), total flavonoid (39.11±2.27 mg/g)] and aqueous fraction [total phenol (140.62±0.57 mg/g), total flavonoid (26.07±1.49 mg/g)] as compared with the chloroform fraction [total phenol (68.56±0.51 mg/g), total flavonoid (13.41±0.82 mg/g)] and petrolium ether fraction [total phenol (36.68±0.43 mg/g), total flavonoid (11.55±1.06 mg/g)]. There was a significant difference in the ARI activity of each fraction, and it was found to be the highest in ethyl acetate fraction [IC50 (49.26±1.76 µg/mL)] followed by aqueous extract [IC50 (70.83±2.82 µg/mL)] and it was least in the petroleum ether fraction [IC50 (118.89±0.71 µg/mL)]. Chloroform fraction showed moderate activity [IC50 (98.52±1.80 µg/mL)]. Different fractions showed significanct amount of ARI activity, where in ethyl acetate fraction it was found to be maximum which may be due to its high phenolic and flavonoid content. The extract after further evaluation may be used in the treatment of diabetic cataract.Asian Pacific Journal of Tropical Biomedicine 02/2012; 2(2):134-9. DOI:10.1016/S2221-1691(11)60207-4
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ABSTRACT: Aldose reductase (AR) has been reported to play an important role in sugar-induced cataract. In the present study, the AR inhibitory activity of Enicostemma hyssopifolium (EH), Gymnema sylvestre, Eclipta alba, and Tinospora cordifolia (TC) were studied along with their effect on sugar-induced cataractogenic changes in sheep lenses in vitro. AR inhibitory activity of the aqueous extracts of plants and their anticataract potentials were evaluated in vitro in sheep lenses, considering the activity of normal sheep lenses as 100%. The concentration of the plant extract that showed maximum activity was selected to further study its effect on galactose-induced polyol accumulation in vitro. The IC 5 0 values of EH and TC were calculated to be 102 and 85 µg/ml, respectively. EH showed a significant inhibition (61.3%) in polyol accumulation followed by TC (53.1%). EH and TC possesses a significant anticataract activity in vitro and its anticataract potential could be related with its AR inhibitory effect.Oriental Pharmacy and Experimental Medicine 09/2009; 9(3):245-251. DOI:10.3742/OPEM.2009.9.3.245