Abstract
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.
Highlights
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 [1]
Compared with the control group, Human lens epithelial cell (HLEC) treated with high-concentration D-gal (250 mM) became swollen, evidenced increased numbers of vacuoles and granules, and demonstrated increased numbers of irregular cells
Following exposure to different syringic acid concentrations, HLECs reverted to normal histology in different degrees
Summary
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 [1]. Though the exact mechanism remains uncertain, a large body of research indicates that aldose reductase (AR) is a key enzyme involved in DC development [2]. 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. AR is contemporarily regarded as an important target for aldose reductase inhibitors (ARI) designed to prevent and treat diabetic cataract and neuropathy, though significant challenges face researchers before clinical implementation is possible [7]
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