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单羟基黄酮对糖基化诱导的晶状体混浊和蛋白质聚集的影响。

Effect of monohydroxylated flavonoids on glycation-induced lens opacity and protein aggregation.

作者信息

Patil Kapil K, Meshram Rohan J, Gacche Rajesh N

机构信息

a School of Life Sciences, Swami Ramanand Teerth Marathwada University , Nanded , Maharashtra , India.

出版信息

J Enzyme Inhib Med Chem. 2016;31(sup1):148-156. doi: 10.1080/14756366.2016.1180593. Epub 2016 May 5.

Abstract

Glycation-induced cataractogenesis and visual impairment is a major ophthalmic concern of altered sugar homeostasis in humans as well as animals. Searching antiglycating agents from natural sources is widely acknowledged as it can be made bioavailable through diet. The present study was designed to understand the positional suitability of hydroxylation in the flavonoid scaffold for maneuvering it as an anticataract agent. Six naturally occurring monohydroxylated flavonoids rataining hydroxylation at 3, 5, 6, 7, 2' and 4' carbon position were evaluated for their effect on glycation induced lens opacity, protein aggregation, carbonyl group formation and nontryptophan fluorescence. The selected flavonoids also evaluated for their aldose reductase inhibition: a key enzyme implicated in cataractogenesis. The results of this study clearly demonstrated the stereo-specificity of hydroxyl substitution and focused the significance of 7-hydroxy substitution as a lead scaffold. Overall, the test flavonoids demonstrated considerable anti-cataract activities in context with studied parameters.

摘要

糖基化诱导的白内障形成和视力损害是人类及动物糖稳态改变所引发的主要眼科问题。从天然来源寻找抗糖基化剂已得到广泛认可,因为它可以通过饮食实现生物利用。本研究旨在了解黄酮类支架中羟基化的位置适宜性,以便将其作为抗白内障药物进行调控。对六种在3、5、6、7、2'和4'碳位置保留羟基化的天然存在的单羟基化黄酮类化合物,评估它们对糖基化诱导的晶状体混浊、蛋白质聚集、羰基形成和非色氨酸荧光的影响。所选黄酮类化合物还评估了它们对醛糖还原酶的抑制作用:醛糖还原酶是一种与白内障形成有关的关键酶。本研究结果清楚地证明了羟基取代的立体特异性,并突出了7-羟基取代作为先导支架的重要性。总体而言,受试黄酮类化合物在所研究的参数方面表现出相当大的抗白内障活性。

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