Search

Objective: To study the anti-cataract effect of gigantol combined with syringic acid and their action mechanism., Method: H202-induced lens oxidative injury in vitro rat model was establish to observe the impact of gigantol combined with syringic acid on lens transparency under a dissecting microscope. D-galactose-induced cataract rat model was established to observe the impact of gigantol combined with syringic acid on lens transparency under a slit-lamp. UV spectrophotometry was adopted to detect the inhibitory activity of gigantol combined with syringic acid against AR. Molecular docking method was used to detect binding sites, binding types and pharmacophores of gigantol combined with syringic acid in prohibiting aldose reductase., Result: Both in vitro and in vivo experiments showed a good anti-sugar cataract activity in the combination of gigantol and syringic acid and a better collaborative effect than single component-gigantol and syringic acid and positive control drug Catalin. Molecular docking and dynamic simulation showed their collaborative AR-inhibiting amino acid residue was Asn160 and the major acting force was Van der Waals' force, which formed common pharmacophores., Conclusion: Gigantol combined with syringic acid shows good anti-cataract, their action mechanism is reflected in their good collaborative inhibitory effect on AR.

Purpose: To compare the chymotrypsin-like and trypsin-like activity of proteasome in the epithelium of human age-related cataract and normal lens, in order to study the mechanism of the proteasome in the formation and development of age-related cataract., Methods: Cataractous lens were obtained during cataract surgery of Zhongshan Ophthalmic Center, and normal age-matched lens were obtained from Guangdong eye bank. The capsules were frozen and thawed repeatedly to ensure the epithelial cells detached from the capsules, then the capsules were removed. All samples were added with LLVY or VGR, then detected the fluorescent intensity at different time., Results: The proteasome activity of normal lens epithelium was significantly high than cataractous lens epithelium (P < 0.01); the chymotrypsin-like activity of the proteasome of cortical and non-cortical cataract had no difference (P > 0.05); MG-132 can significantly inhibit the proteasome activity of cataractous and normal lens., Conclusion: Compared to normal age-matched lens, chymotrypsin-like and trypsin-like activity of proteasome in the epithelium of age-related cataract lens were significantly declined, indicating that the decrease of the proteasome activity may play an important role in the formation and development of age-related cataract.

Objective: To investigate the effect of antioxidants N-acetyl-L-cysteine and catalase on H(2)O(2)-induced apoptosis of lens epithelial cells and the activity of caspase-3., Methods: Rat lenses were incubated in MEM with 2 mmol/L H(2)O(2) (H(2)O(2) groups) or without H(2)O(2) (control groups), antioxidants 100 micromol/L N-acetyl-L-cysteine and 900 U/ml catalase were used to block the oxidative injury of lens epithelial cells respectively. Lens opacification and apoptosis of lens epithelial cells were detected using transmission electron microscope and AnnexinV-PI staining after 24 hours incubation. The activity of caspase-3 was analyzed by Western blot at the same time., Results: The observations revealed that 2 mmol/L H(2)O(2) could apparently induce lens opacification and lens epithelial cell apoptosis in vitro, the apoptosis rate increased to (31.20 +/- 3.31)% after 24 hours incubation, which is also the time caspase-3 was activated. Treatment with N-acetyl-L-cysteine and catalase could inhibit lens opacification, apoptosis and caspase-3 activation induced by H(2)O(2). The apoptosis rate decreased to (20.90 +/- 3.16)% and (15.02 +/- 2.41)% respectively (P < 0.01)., Conclusion: These data indicate that antioxidants N-acetyl-L-cysteine and catalase, possibly through regulation of the activity of caspase-3, can prevent lens opacification and apoptosis of lens epithelial cells.

This study was designed to evaluate the changes and the role of lens epithelium in sugar cataract formation, in regard to the fact that the highest level of aldose reductase is found in this layer of lens. By light and electron microscopy, we examined the histological changes of central epithelium in lens of rats made diabetic with streptozotocin (STZ) with or without AL1576, an aldose reductase inhibitor, at varying periods of time ranging from 5 to 40 days after intraperitoneal injection of STZ. Also, we examined Na-K-ATPase activity in lens epithelium of rats with diabetes, diabetes plus AL1576 and normal controls at the time of 30 days. The results showed that the first detectable abnormalities occurred after 15 days of STZ injection and were limited to the lens epithelium; cell edema, intracellular vacuoles and extention of rough endoplasmic reticulum pool were remarkable; that AL1576 could prevent almost all of the lesion mentioned above; and that Na-K-ATPase activity in lens epithelium of rats with diabetes increased at the time of 30 days. The findings suggest that lens epithelium may play an important role in sugar cataractogenesis.

Seven Chinese herbal drugs were screened for experimental inhibition of lens aldose reductase activity, among which quercetin exhibited potent enzyme-inhibitory activities in vitro. Its IC50 value was 3.44 x 10(-7) mol/L. It may be helpful in the prophylaxis and treatment of diabetic complications.

Nearly 20 herbs or herbal components were screened for the inhibitory effect of rat lens aldose reductase(AR) with a fluorometric assay of AR activity. Among these Glycyrrhiza uralensis, Salvia miltiorrhiza, Radix astragali, Gentiana scabra, silybin, puerarin and baicalin were found to exhibit markedly inhibitory effects on AR comparable to Sorbinil. The authors suggest that some of the Chinese herbs used in the control of diabetic complications may act through the pharmacologic action of inhibiting AR.