ZN(ii)与阿魏酸的配合物增强了有前途的抗糖尿病和抗氧化协同作用：多模式研究。

Complexation potentiated promising anti-diabetic and anti-oxidative synergism between ZN(ii) and ferulic acid: A multimode study.

机构信息

Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein, Free State, South Africa.

Centre for Quality of Health and Living (CQHL), Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein, Free State, South Africa.

出版信息

Diabet Med. 2022 Sep;39(9):e14905. doi: 10.1111/dme.14905. Epub 2022 Jul 6.

DOI:10.1111/dme.14905

PMID:35748705

Abstract

AIM

This study was done to investigate the anti-diabetic and anti-oxidative synergism between zinc(II) and ferulic acid through complexation.

METHODS

Zinc sulphate was complexed with ferulic acid in a 1:2 molar ratio. The complex was characterized using Fourier-transform infrared spectroscopy, proton NMR and high-resolution mass spectroscopy techniques and evaluated for cellular toxicity. In silico, in vitro, cell-based and tissue experimental models were used to test the anti-diabetic and anti-oxidant activities of the complex relative to its precursors.

RESULTS

A zinc(II)-biferulate.2H O complex was formed. The in vitro radical scavenging, anti-lipid peroxidative and α-glucosidase and α-amylase inhibitory activity of the complex was 1.7-2.1 folds more potent than ferulic acid. Zn(II) complexation increased the anti-glycation activity of ferulic acid by 1.5 folds. The complex suppressed lipid peroxidation (IC = 48.6 and 331 μM) and GHS depletion (IC = 33.9 and 33.5 μM) in both Chang liver cells and isolated rat liver tissue. Its activity was 2.3-3.3 folds more potent than ferulic acid and statistically comparable to ascorbic acid. Zn(II) complexation afforded ferulic acid improved glucose uptake activity in L-6 myotube (EC = 11.7 vs. 45.7 μM) and isolated rat muscle tissue (EC = 501 and 1510 μM). Complexation increased muscle tissue zinc(II) uptake and hexokinase activity. Docking scores of the complex (-7.24 to -8.25 kcal/mol) and ferulic acid (-5.75 to 6.43 kcal/mol) suggest the complex had stronger interaction with protein targets related to diabetes, which may be attributed to the 2 ferulic acid moieties and Zn(II) in the complex. Moreover, muscle tissue showed increased phospho-Akt/pan-Akt ratio upon treatment with complex. The complex was not hepatotoxic and myotoxic at in vitro cellular level.

CONCLUSION

Zn(II) complexation may be promising therapeutic approach for improving the glycaemic control and anti-oxidative potential of natural phenolic acids.

摘要

目的

本研究旨在通过螯合作用研究锌（II）和阿魏酸之间的抗糖尿病和抗氧化协同作用。

方法

硫酸锌与阿魏酸以 1:2 的摩尔比络合。使用傅里叶变换红外光谱、质子 NMR 和高分辨率质谱技术对配合物进行表征，并评估其细胞毒性。使用基于细胞和组织的体内、体外实验模型，相对于其前体测试配合物的抗糖尿病和抗氧化活性。

结果

形成了锌（II）-阿魏酸.2H 2 O 配合物。该配合物的体外自由基清除、抗脂质过氧化、α-葡萄糖苷酶和α-淀粉酶抑制活性比阿魏酸强 1.7-2.1 倍。Zn（II）络合使阿魏酸的抗糖化活性增加了 1.5 倍。该配合物抑制 Chang 肝细胞和分离大鼠肝组织中的脂质过氧化（IC 50 分别为 48.6 和 331μM）和 GSH 耗竭（IC 50 分别为 33.9 和 33.5μM）。其活性比阿魏酸强 2.3-3.3 倍，与抗坏血酸相当。Zn（II）络合使阿魏酸在 L-6 肌管（EC 50 分别为 11.7 和 45.7μM）和分离的大鼠肌肉组织（EC 50 分别为 501 和 1510μM）中的葡萄糖摄取活性增强。络合增加了肌肉组织中的锌（II）摄取和己糖激酶活性。配合物（-7.24 至-8.25kcal/mol）和阿魏酸（-5.75 至 6.43kcal/mol）的对接分数表明，该配合物与与糖尿病相关的蛋白质靶标具有更强的相互作用，这可能归因于配合物中的 2 个阿魏酸部分和 Zn（II）。此外，肌肉组织在接受配合物治疗后磷酸化 Akt/总 Akt 比值增加。该配合物在体外细胞水平上无肝毒性和肌毒性。