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目的:探讨石斛酚和丁香酸联合对抗白内障作用并探讨其作用机制。方法:H2O2致离体培养的氧化损伤大鼠晶状体模型,解剖显微镜下观察石斛酚和丁香酸联合对晶状体的透明度的影响;D-半乳糖致糖性白内障大鼠模型,裂隙灯观察石斛酚和丁香酸联合对在体大鼠晶状体透明度的影响;采用紫外分光光度法表征石斛酚和丁香酸联合对醛糖还原酶(AR)的抑制活性;采用分子对接考察石斛酚和丁香酸联合抑制AR的结合位点、结合方式及其药效团。结果:离体及在体实验均表明石斛酚和丁香酸组合具有良好的抗糖性白内障活性,且优于单一组分石斛酚和丁香酸及阳性对照药物白内停,表现良好的协同效果;分子对接及动力学模拟表明二者协同抑制AR的氨基酸残基为Asn160,主要作用力为范德华力,形成共同药效团。结论:石斛酚与丁香酸联合具有良好的抗白内障活性,其作用机制在于二者对AR呈现良好的协同抑制性。
Objective: To investigate the combined effect of gigantol and syringic acid against cataract and to explore its mechanism. Methods: The oxidative damage induced by H2O2 in rat lens model was observed under a dissecting microscope. The effects of the combination of gigantol and syringic acid on the transparency of the lens were observed under microscope. D-galactose-induced cataract induced rat model of cataract. Syringic acid on the transparency of the lens in vivo in rats; UV spectrophotometry was used to characterize the inhibition of aldose reductase (AR) by the combination of gigantol and syringic acid; the molecular docking was used to examine the effects of gigantol and syringic acid on the inhibition of AR Binding sites, binding methods and their pharmacophores. RESULTS: Both in vitro and in vivo experiments showed that the combination of gigantol and syringic acid had good anti-glycogenic cataract activity and was superior to the single component of gigantol and syringic acid and the positive control drug levofloxacin, showing good synergistic effect. Molecular docking and kinetic modeling show that the two inhibit the amino acid residues of AR as Asn160, the main force is van der Waals forces, forming a common pharmacophore. CONCLUSION: The combination of gigantol and syringic acid has good anti-cataract activity. The mechanism of action is that both of them show a good synergistic inhibitory effect on AR.