石斛酚与丁香酸联合抗白内障作用及其机制研究

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。

Study on anti-cataract effect of gigantol combined with syringic acid and their mechanism

Objective : To study the anti-cataract effect of gigantol combined with syringic acid and their action mechanism. Method : H₂O₂-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.