Objective. Effects of Syringic acid (SA) extracted from dendrobii on diabetic cataract (DC) pathogenesis were explored. Methods. Both in vitro and in vivo DC lens models were established using D-gal, and proliferation of HLEC exposed to SA was determined by MMT assay. After 60-day treatment with SA, rat lens transparency was observed by anatomical microscopy using a slit lamp. SA protein targets were extracted and isolated using 2-DE and MALDI TOF/TOF. AR gene expression was investigated using qRT-PCR. Interaction sites and binding characteristics were determined by molecule-docking techniques and dynamic models. Results. Targeting AR, SA provided protection from D-gal-induced damage by consistently maintaining lens transparency and delaying lens turbidity development. Inhibition of AR gene expression by SA was confirmed by qRT-PCR. IC50 of SA for inhibition of AR activity was 213.17？μg/mL. AR-SA binding sites were Trp111, His110, Tyr48, Trp20, Trp79, Leu300, and Phe122. The main binding modes involved hydrophobic interactions and hydrogen bonding. The stoichiometric ratio of non-covalent bonding between SA and AR was 1.0 to 13.3. Conclusion. SA acts to prevent DC in rat lenses by inhibiting AR activity and gene expression, which has potential to be developed into a novel drug for therapeutic management of DC. 1. Introduction Increasing population senescence due to improved living standards and diet has increased the incidence rate of diabetic cataract, a frequent cause of vision impairment and blindness . A complex pathogenic mechanism underlies diabetic cataract. Though the exact mechanism remains uncertain, a large body of research indicates that aldose reductase (AR) is a key enzyme involved in DC development . In order to reduce diabetic cataract incidence and slow the progression of diabetic cataract in current patients, further understanding of the mechanistic involvement of AR in diabetic cataract development and progression is required. In diabetic patients, AR activation increases polyalcohol metabolism rates. As a result, glucitol accumulation in the eye caused increased osmotic pressure, alterations to cell membrane permeability, edema, and damage to cells of the optical lens. These changes block the passage of nutrients into the lens, further resulting in reduced amino acid levels accompanied by protein denaturation and polymerization. The end result of this process is cataract formation and progression . Previous studies of the experimental aldose reductase inhibitors GP-1447 and KIOM-79 have demonstrated a relationship between AR
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