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.
The polyol enzyme aldose reductase (AR) and advanced glycation endproducts (AGEs) play an important role in diabetic complications such as cataracts. The purpose of this study was to investigate four standardized plant extracts used for the treatment of diabetes and related diseases, and their principal components for AR inhibitory activity and to find out their influence in diabetic complications. Thus, Boswellia serrata Triana & Planch. (Burseraceae), Lagerstroemia speciosa (L.) Pers. (Lythraceae), Ocimum gratissimum (L.) (Lamiaceae) and Syzygium cumin (L.) Skeels. (Myrthaceae) and their respective major constituents, boswellic acid, corosolic acid, ursolic acid and ellagic acid, were studied for their inhibitory activity against rat lens AR, rat kidney AR, human recombinant AR and generation of AGEs. In addition, in vivo inhibition of lens galactitol accumulation by the major constituents of the plants in galactose-fed rat has been studied. The results revealed that all the tested extracts and their active ingredients possess significant AR inhibitory actions in both in vitro and in vivo assays with urosolic acid showing the most potent effect. Furthermore, the study indicates the potential of the studied plants and their major constituents as possible protective agents against long-term diabetic complications.
Aldose reductase is the first enzyme in the polyol pathway and catalyzes the reduction of glucose to sorbitol by coupling with the oxidation of NADPH to NADP(+) . This sorbitol accumulation leads to various diabetic complications, including neuropathy, nephropathy, cataracts, and retinopathy. In the present study, aldose reductase inhibitory (ARI) activity of the methanolic as well as standardized extracts of Andrographis paniculata (Burm. f.) Wall. ex Nees (Acanthaceae) and its chief constituent, andrographolide, were studied using in vitro and in vivo methods. In the in vitro method, rat lens as well as kidney homogenates were used for the preparation of enzyme, whereas the effect of these test samples on the galactitol level in the eye lens was studied in a galactosemic rat model in vivo. The results of the study revealed that both extracts of the plant and its major compound, andrographolide, possess ARI activity in vitro. They were also found to significantly decrease galactitol accumulation in vivo.
Objective: The objectives were to study the in-vitro and in-vivo aldose reductase and in-vitro advanced glycation end products formation inhibitory activities of the standardized extracts of Picrorhiza kurroa roots and Hibiscus rosa-sinensis flowers.
Methods:In-vitro Aldose reductase inhibitory activity was studied by using isolated rat lens and kidney Aldose reductase by UV-Visible spectro photo metric method by using Quercetin as reference compound. In-vivo Aldose reductase inhibitory activity was evaluated by using experimental rat models of galactosemia and the final lens galactitol was evaluated by High performance liquid chromatography and Gas chromatography methods by using Quercetin as reference compound. Invitro advanced glycation end products formation inhibitory activity was estimated by using laboratory test reaction with protein and sugars by spectro fluorimetric method by sung aminoguanidine as reference compound. Statistical analysis of the results was done by using Analysis of the variance method.
Results:The plant extracts were found to possess significant aldose reductase and advanced glycation end products formation inhibitory activity.
Conclusions:More study is required for isolation and characterization of the chief chemical constituents responsible for the biological activity of the plant extracts.
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