Department of Health Sciences, Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9301, Free State, South Africa; Centre for Quality of Health and Living (CQHL), Faculty of Health and Environmental Sciences, Central University of Technology, Bloemfontein 9301, Free State, South Africa.
Division of Microbiology & NCDs, ICMR-Regional Medical Research Centre, 751023 Odisha, India.
Biomed Pharmacother. 2022 Oct;154:113600. doi: 10.1016/j.biopha.2022.113600. Epub 2022 Aug 26.
Zinc and syringic acid have metabolic and antioxidant medicinal potentials. A novel zinc(II)-syringic acid complex with improved anti-hyperglycaemic and antioxidant potential was developed. Zinc(II) was complexed with syringic acid in a 1:2 molar ratio and characterized using FT-IR, H NMR and LC-MS. Different experimental models were used to compare the anti-hyperglycaemic and antioxidant properties between the complex and precursors. A Zn(II)-bisyringate.2HO complex was formed. The in vitro radical scavenging and Fe reducing antioxidant, antiglycation, and α-glucosidase inhibitory activities of the complex were 1.8-5.2 folds stronger than those of the syringic acid precursor and comparable to those of the positive controls. The complex possessed an increased ability to inhibit lipid peroxidation (by 1.6-1.7 folds) and glutathione depletion (2.8-3 folds) relative to syringic acid in Chang liver cells and liver tissues isolated from rats. The complex exhibited a higher glucose uptake effect (EC = 20.4 and 386 µM) than its precursors (EC = 71.1 and 6460 µM) in L6-myotubes and psoas muscle tissues isolated from rats, respectively, which may be linked to the observed increased cellular zinc uptake potentiated by complexation. Tissue glucose uptake activity was accompanied by increased hexokinase activity, suggesting increased glucose utilization. Moreover, treatment increased tissue phospho-Akt/pan-Akt ratio. The complex had strong molecular docking scores than syringic acid with target proteins linked to diabetes. The presence of two syringic acid moieties and Zn(II) in the complex influenced its potency. The complex was not hepatotoxic and myotoxic in vitro. Zinc-syringic acid complexation may be a novel promising therapeutic approach for diabetes and oxidative complications.
锌和丁香酸具有代谢和抗氧化的药用潜力。开发了一种具有改善的抗高血糖和抗氧化潜力的新型锌（II）-丁香酸配合物。锌（II）与丁香酸以 1:2 的摩尔比配位，并通过 FT-IR、H NMR 和 LC-MS 进行了表征。使用不同的实验模型比较了配合物与前体的抗高血糖和抗氧化特性。形成了 Zn(II)-双丁香酸.2HO 配合物。该配合物的体外自由基清除和 Fe 还原抗氧化、抗糖化和α-葡萄糖苷酶抑制活性比丁香酸前体强 1.8-5.2 倍，与阳性对照相当。与丁香酸相比，该配合物在 Chang 肝细胞和大鼠肝脏组织中抑制脂质过氧化（提高 1.6-1.7 倍）和谷胱甘肽耗竭（提高 2.8-3 倍）的能力增强。与前体（L6 肌管中的 EC = 71.1 和 6460 μM，大鼠 psoas 肌肉组织中的 EC = 386 和 6460 μM）相比，该配合物在 L6 肌管和大鼠 psoas 肌肉组织中具有更高的葡萄糖摄取作用（EC = 20.4 和 386 μM），这可能与观察到的配合物增强的细胞锌摄取有关。组织葡萄糖摄取活性伴随着己糖激酶活性的增加，表明葡萄糖利用增加。此外，治疗还增加了组织磷酸化 Akt/总 Akt 比值。该配合物与与糖尿病相关的靶蛋白的分子对接评分强于丁香酸。配合物中两个丁香酸部分和 Zn(II)的存在影响了其效力。该配合物在体外对肝脏和肌肉无毒。锌-丁香酸配合物可能是治疗糖尿病和氧化并发症的一种有前途的新方法。
