Reversal of Diabetic Cataract by Sorbinil, an Aldose Reductase Inhibitor

Abstract

Aldose reductase is implicated in the pathogenesis of diabetic cataracts; therefore, inhibition of this enzyme subsequent to cataractogenesis may represent a therapeutic approach for restoration of lens physiology. In the present study, the effect of aldose reductase inhibition subsequent to stage I cataract formation was investigated in the streptozocin-induced diabetic rat. Our results indicated that the aldose reductase inhibitor sorbinil, a spirohydantoin, arrested further progression and promoted a reparative process despite continuation of hyperglycemia and elevated lens glucose. Quantitative analysis of scanning electron micrographs indicated that the afflicted lens regions were contained and their cellular components stabilized with regard to fiber hydration and interdigitation. The reparative process included: normalization of lens sorbitol, gradual recovery of existing fiber contour and interdigitation, production of new fibers, and partial restoration of lens myo-inositol content.

Anthraquinones from the Seeds of Cassia tora with Inhibitory Activity on Protein Glycation and Aldose Reductase

“…Nine anthraquinones, aurantio-obtusin (1), chryso-obtusin (2), obtusin (3), chryso-obtusin-2-O-b-D-glucoside (4), physcion (5), emodin (6), chrysophanol (7), obtusifolin (8), and obtusifolin-2-O-b-D-glucoside (9) were isolated from an EtOAc-soluble extract of the seeds of Cassia tora. The structures of the known compounds were identified by physical and spectroscopic data (mp, 1 H-, 13 C-NMR, and MS) measurement and by comparison with published values.…”

“…18) Previous phytochemical investigation on the seeds of C. tora have resulted in the isolation of several anthraquinone and naphthopyrone derivatives. 13,[16][17][18][19][20] In the present study, further fractionation of the EtOAc-soluble extract of the seeds of C. tora led to the purification of nine anthraquinones (1)(2)(3)(4)(5)(6)(7)(8)(9). The structures of 1-9 were determined by spectroscopic data interpretation and they were subjected to in vitro bioassays to evaluate their inhibitory activity against AGEs and RLAR.…”

“…7) Aldose reductase (AR), the key enzyme in the polyol pathway, also has been demonstrated to play important roles in the pathogenesis of diabetic complications and cataract formation. 8) Thus, the design and discovery of inhibitors of AGEs formation or AR can offer a promising therapeutic approach for the prevention of diabetic or other pathogenic complications. 9,10) In our ongoing project directed toward the discovery of preventive agents for diabetic complications from the herbal medicines, 11) the seeds of Cassia tora was chosen for more detailed investigation, since the EtOAc-soluble fraction of a MeOH extract showed a significant in vitro inhibitory effect on AGEs.…”

Epalrestat Upregulates Heme Oxygenase-1, Superoxide Dismutase, and Catalase in Cells of the Nervous System

“…25) Therefore, the EPS-stimulated Nrf2 activation is most likely achieved by altering Keap1 structure. Unlike EPS, other aldose reductase inhibitors, such as sorbinil and alrestatin, 26,27) failed to increase HO-1 levels (data not shown). This result indicates that sorbinil and alrestatin, which do not have an α,β-unsaturated aldehyde or ketone, have no influence on the Nrf2 pathway.…”

Inhibitory Effects of Isorhamnetin-3-O-.BETA.-D-glucoside from Salicornia herbacea on Rat Lens Aldose Reductase and Sorbitol Accumulation in Streptozotocin-Induced Diabetic Rat Tissues

“…3) Evidence suggests that compounds that inhibit AR could be effective in the prevention of diabetic complications. A number of structurally diverse naturally occurring and synthetic AR inhibitors have been studied in vivo to clarify their effectiveness in the prevention of diabetic complications in experimental animals, 4) as well as in clinical trials. 5) Specific inhibitors of the enzyme may be therapeutically attractive agents for the prevention and/or treatment of diabetic complications.…”