新型 Zn(II)-肉桂酸配合物的降血糖和抗氧化性能。

Antidiabetic and Antioxidative Properties of Novel Zn(II)-cinnamic Acid Complex.

机构信息

Centre on Quality of Health and Living (CQHL), Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein, 9300, Free State, South Africa.

Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein, 9300, Free State, South Africa.

出版信息

Med Chem. 2021;17(8):913-925. doi: 10.2174/1573406416666200929143257.

DOI:10.2174/1573406416666200929143257

PMID:32990538

Abstract

BACKGROUND

The role of zinc in diabetes has been a subject of considerable interest due to the insulin-mimetic properties associated with this mineral. On the other hand, phenolic acids are known as plant-derived polyphenols with antioxidative and antidiabetic pharmacological credence.

OBJECTIVE

This study was conducted in order to develop a novel therapeutic nutraceutical with an improved and multi-mode antidiabetic and antioxidative pharmacological property using cinnamic acid and Zn(II) mineral framework.

METHODS

A Zn(II) acetate complex of cinnamic acid was synthesized and characterized using FT-IR and HNMR spectroscopy. Cytotoxicity evaluation was done using Chang liver cells and differentiated L6 myotubes. DPPH and ABTS scavenging, as well as Fe reducing effects, were used to evaluate the antioxidant capacity. The antiglycation, as well as α-glucosidase and α-amylase inhibitory properties, were evaluated. Insulin mimetic property was evaluated as glucose uptake in L6 myotubes, while the complex was docked against GLUT-4 and PKB.

RESULTS

FTIR and HMR suggested that Zn(II) complexed with cinnamic acid through a Zn(O) coordination mode, thus affording the resulting complex 2 cinnamic acid molecules. Hence, complexation increased (p ˂ 0.05) the antiglycation effect of cinnamic acid (IC = 29.3 μM) by 2 folds (IC = 13.9 μM). Also, Zn(II) conferred a potent glucose uptake (EC = 31 μM) and α-glucosidase inhibitory (IC = 59.4 μM) property on cinnamic acid; hence the activity of the complex was 162 and 2.1 folds higher than (p ˂ 0.05) its precursor, respectively. Further molecular docking studies showed that the complex had a stronger interaction with insulin signaling proteins (GLUT-4 and PKB) than its precursor. Interestingly, the complex showed no severe cytotoxicity.

CONCLUSION

Data suggested a structure-activity relationship. Complexation of Zn(II) to cinnamic acid resulted in a complex with improved and multi-facet pharmacological effects, which may be further studied as a safe glycemic control nutraceutical for T2D and glycation-induced complications.

摘要

背景

锌在糖尿病中的作用一直是一个备受关注的话题，因为这种矿物质具有胰岛素模拟特性。另一方面，酚酸是一种已知的植物来源的多酚，具有抗氧化和抗糖尿病的药理学作用。

目的

本研究旨在开发一种新型治疗性营养保健品，该保健品具有改良的多模式抗糖尿病和抗氧化药理学特性，使用肉桂酸和 Zn(II) 矿物质框架。

方法

使用傅里叶变换红外光谱（FT-IR）和核磁共振氢谱（HNMR）光谱合成并表征肉桂酸的 Zn(II) 醋酸盐络合物。使用 Chang 肝细胞和分化的 L6 肌管评估细胞毒性。使用 DPPH 和 ABTS 清除以及铁还原作用评估抗氧化能力。评估了该络合物的抗糖化、α-葡萄糖苷酶和α-淀粉酶抑制特性。胰岛素模拟特性通过 L6 肌管中的葡萄糖摄取进行评估，同时将该络合物对接 GLUT-4 和 PKB。

结果

FTIR 和 HMR 表明，Zn(II) 通过 Zn(O) 配位模式与肉桂酸络合，从而使所得络合物与 2 个肉桂酸分子配位。因此，络合作用将肉桂酸的抗糖化作用（IC = 29.3 μM）提高了 2 倍（IC = 13.9 μM）（p ˂ 0.05）。此外，Zn(II) 赋予肉桂酸（EC = 31 μM）和 α-葡萄糖苷酶抑制作用（IC = 59.4 μM），因此，其活性分别比其前体高 162 倍和 2.1 倍（p ˂ 0.05）。进一步的分子对接研究表明，该络合物与胰岛素信号蛋白（GLUT-4 和 PKB）的相互作用强于其前体。有趣的是，该络合物没有严重的细胞毒性。