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罗斯科的药理活性:对人血清白蛋白蛋白糖基化的抑制、结构稳定性及功能恢复

Pharmacological Activities of Roscoe: Inhibition of HSA Protein Glycation, Structure Stability and Function Restoration.

作者信息

Khan Mohd Wajid Ali, Sherwani Subuhi, Alshammari Muna H E, Alsukaibi Abdulmohsen K D, Khan Wahid Ali, Haque Ashanul, Alenezi Khalaf M, Shahab Uzma

机构信息

Department of Chemistry, College of Sciences, University of Ha'il, Ha'il 55473, Saudi Arabia.

Medical and Diagnostic Research Center, University of Ha'il, Ha'il 55473, Saudi Arabia.

出版信息

Pharmaceuticals (Basel). 2024 Nov 1;17(11):1469. doi: 10.3390/ph17111469.

Abstract

BACKGROUND

Controlled non-enzymatic glycation reactions are common under normal physiological conditions. However, during elevated blood glucose conditions, the glycation reactions are accelerated, leading to the formation of toxic compounds such as advanced glycation end products (AGEs). Several natural products are now being investigated as protective agents against glycation to preserve blood protein structure and functions.

METHODS

Human serum albumin (HSA) was glycated with 0.05 M α-D-glucose alone or in the presence of Roscoe (ginger) extract (0.781-100 μg/mL) for 10 weeks, and biochemical, biophysical, and computational analyses were carried out.

RESULTS

HSA glycated for 10 weeks (G-HSA-10W) resulted in significant production of ketoamines, carbonyl compounds, and AGE pentosidine. Notable structural alterations were observed in G-HSA-10W, ascertained by ultraviolet (UV), fluorescence, and circular dichroism (CD) studies. Antioxidant, anti-glycating, AGEs inhibitory, and antibacterial effects of ginger extracts were observed and attributed to the presence of various phytochemicals. Molecular docking studies suggested that the compounds 8-shagaol and gingerol exhibited strong and multiple interactions with HSA. Molecular simulation analysis suggests HSA attains a high degree of conformational stability with the compounds gingerol and 8-shogaol.

CONCLUSIONS

These findings showed that ginger extract has an antioxidant function and can prevent glycation-induced biochemical and biophysical alterations in HSA. Thus, aqueous ginger extract can be utilized to combat glycation and AGE-related health issues, especially diabetes, neurological disorders, inflammatory diseases, etc.

摘要

背景

在正常生理条件下,非酶糖基化反应是常见的。然而,在血糖升高的情况下,糖基化反应会加速,导致形成诸如晚期糖基化终产物(AGEs)等有毒化合物。目前正在研究几种天然产物作为抗糖基化的保护剂,以维持血液蛋白质的结构和功能。

方法

将人血清白蛋白(HSA)单独与0.05Mα-D-葡萄糖或在存在罗斯科(姜)提取物(0.781 - 100μg/mL)的情况下糖基化10周,并进行生化、生物物理和计算分析。

结果

糖基化10周的HSA(G-HSA-10W)导致显著产生酮胺、羰基化合物和AGE戊糖苷。通过紫外(UV)、荧光和圆二色性(CD)研究确定,在G-HSA-10W中观察到了明显的结构改变。观察到姜提取物具有抗氧化、抗糖基化、AGEs抑制和抗菌作用,这归因于各种植物化学物质的存在。分子对接研究表明,化合物8-姜辣烯酮和姜辣素与HSA表现出强烈且多样的相互作用。分子模拟分析表明,HSA与化合物姜辣素和8-姜辣烯酮具有高度的构象稳定性。

结论

这些发现表明,姜提取物具有抗氧化功能,可以防止HSA中糖基化诱导的生化和生物物理改变。因此,姜的水提取物可用于对抗糖基化和与AGE相关的健康问题,特别是糖尿病、神经紊乱、炎症性疾病等。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02c2/11597160/85938e96c93b/pharmaceuticals-17-01469-g001.jpg

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