Rat lens aldose reductase

Lee H-S. (2002) Rat lens aldose reductase inhibitory activities of Coptis japonica root-derived isoquinoline alkaloids. JAgric Food Chem 50 7013-7016. 

Matsuda H, Morikawa T, Toguchida 1, Harima S, Yoshikawa M. (2002) 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. Chem Pharm Bull 50 972-975. 

Lee YS, Lee S, Lee HS, Kim B-K, Ohuchi K, Shin KH. (2005) Inhibitory effects of isorhamnetin-3-O-P-D-glucoside from Salicornia herbacea on rat lens aldose reductase and sorbitol accumulation in streptozotocin-induced diabetic rat tissues. Biol Pharm Bull 28 916-918. 

Lee, H.S. (2002) Inhibitory activity of Cinnamomum cassia bark derived component against rat lens aldose reductase. Journal of Pharmacy and Pharmaceutical Sciences 5, 226-230. 

Garcinia kola Heckel (seeds) 3",4, 4", 5,5",7,7"-Heptahydroxy-3,8-biflavanone (GBi) (176) GB2 (177) Kolaviron (KV) [a mixture of (C-3,C-8)-linked biflavonoids GBi (177) + GB2 (177) + kolaflavanone (178)]. Traditional medicine in the West and Central African sub-region. Poison antidote. Seeds have been used in traditional African medicine to treat diabetes. Antioxidant and antihepatotoxic properties. KV showed antioxidant, hepatoprotective and hypoglycaemic effects. KV inhibited rat lens aldose reductase (RLAR) activity, had antidiabetic and hypolipidaemic effects, and showed immunomodulatory and immunorestorative properties. Maurice, 1982[186] Iwu et al., 1987[187], 1990[101] Farombi et al., 2000[188] Adefule-Ositelu et al., 2004[189] Adaramo ye and Adeyemi, 2006[190, 191] Nworu et al., 2008[192] Okoko, 2009[113]. 

In connection with the finding that perilloside A 17 inhibits rat lens aldose reductase, an extensive range of monoterpene glucosides and their tetraacetates have been synthesized by standard Koenigs-Knorr methods, and the same approach has been used to prepare the 3- and 25-monoglucuronides of 25-... 

The triterpenoid constituents, 3p,22(3-dihydroxyolean-12-en-29-oic acid (85), tingenone (86), tingenine B (87 22(3-hydroxytingenone), regeol A (88) and triptocalline A (89) isolated from Salacia chinensis L. (family Celastraceae), were examined on rat lens for aldose reductase inhibitory activity the test compounds 85-89 were evaluated to exhibit rat lens aldose reducatse inhibitory activity with IC50 values of 26,13, 7.0,30, and 14 /rM, respectively. ... 

The inhibitory activities of 1 l-oxopyrido[2,l-i>]quinazolinecarboxylic acids on rat lens and human placental aldose reductase were studied. From the specific structural and electronic similarities of diverse aldose reductate inhibitors the pharmacophor requirements for an inhibitor were postulated. ... 

Ou, P, Nourooz-Zadeh J, Tritschler HJ, Wolff S. Activation of aldose reductase in rat lens and metal-ion chelation by aldose reductase inhibitors and lipoic acid. Free Radical Res 1996 25 337-346. 

The roots of S. oblonga have been extensively used for the treatment of diabetes in the Ayurvedic system of traditional Indian medicine. From the ethyl acetate soluble portion of the methanolic extract from the roots of S. oblonga Matsuda et al. isolated compound (14), a friedelane-type triterpene [42]. The methanolic extract and the ethyl acetate soluble portions were found to show inhibitory activity on aldose reductase, which is related to chronic diabetes complications such as peripheral neuropathy, retinopathy and cataracts. Compound (14) was assayed for aldose reductase rat lens inhibitory activity. It showed inhibition percentages of 21.8 % at a concentration of 30 pM and 48.2 % at a concentration of 100 pM. The activity of (14) and other terpenoids isolated from this plant could prove to be the reason for the popular use of the plant in the Ayurvedic system for the treatment of diabetes. 

Tetramethyleneglutaric acid (TMG) (62) and alrestatin (AY-22,284) (63)) are known aldose reductase inhibitors. From natural products, a number of flavonoids have been reported to have aldose reductase inhibitory activity. Quercetin (64 1, R = H), quercitrin (64 2, R = L-rhamnose), rutin (64 3, R = rutinose (6-O-a -L-rhamnosyl-D-glucose)) and myricitrin (65 2, R = L-rhamnose) were much more effective inhibitors of aldose reductase from rat lens than TMG (62) and alrestatin (63) [66]. Quercetin with 3, 4 -dihydroxy substitution in ring C was more potent... 

Tissue Location and Role of Aldose Reductase in Animal Models of Diabetic Complications. Aldose reductase (AR) has been located immunohistochemically in many tissues of the dog and rat, most notably, in corneal epithelium, retina, optic nerve, kidney papillae, aortic endothelium and smooth muscle cells as well as peripheral nerve and lens. AR has also been measured in human and monkey retinal mural cells. These cells are thought to provide the structural support for retinal capillaries and their loss is the first abnormality seen in clinical diabetic retinopathy. In addition, AR-like activity has been reported in a human retinoblastoma cell line and sorbinil inhibits this activity in these cells. Finally, a recent report has demonstrated that AR is present in isolated capillaries from bovine retina and cerebral cortex. Therefore, AR appears to be present in all tissues which are uniquely susceptible to deterioration during prolonged exposure to the hyperglycemia of diabetes. Accumulation of the products of the polyol pathway, sorbitol and fructose, has been demonstrated in these tissues and, where tested, sorbinil and other AR inhibitors have been shown to inhibit this accumulation. 

In these coupled reactions, the overall transformation of glucose to fructose is accompanied by a transfer of hydrogen from NADPH to NAD. Studies on the activity of aldose reductase and sorbitol dehydrogenase as well as the presence of sorbitol in seminal vesicles of several species and rat coagulating gland are consistent with the operation of the sorbitol pathway as a major determinant of seminal fructose biosynthesis (248, 252-260). Nonphosphorylative conversion of glucose to sorbitol has also been demonstrated in placenta (258, 261, 262), smooth muscle of the aorta (263), the lens of the eye (264, 265), erythrocytes (266) and hepatoma-derived (HTC) cells in culture (267), and possibly normal liver cells (267, 268). 

Spontaneous diabetic rats are less suitable for toxicological research, because the onset of a diabetes cannot be influenced. This reduces the repro-ducibility of cataract formation, because during aging, the lens becomes less sensitive to glucose due to an age-dependend decrease in activity of aldose-reductase. This slows down the formation of the diabetic cataract. 

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