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血管保护剂抑制非酶性蛋白质糖基化、活性羰基和氧自由基吸收的潜力。

Potential of Vasoprotectives to Inhibit Non-Enzymatic Protein Glycation, and Reactive Carbonyl and Oxygen Species Uptake.

机构信息

Department of Pharmacognosy and Herbal Medicines, Faculty of Pharmacy, Wroclaw Medical University, ul. Borowska 211, 50-556 Wroclaw, Poland.

出版信息

Int J Mol Sci. 2021 Sep 16;22(18):10026. doi: 10.3390/ijms221810026.

Abstract

Reactive carbonyl species (RCS) such as methylglyoxal (MGO) or glyoxal (GO) are the main precursors of the formation of advanced glycation end products (AGEs). AGEs are a major factor in the development of vascular complications in diabetes. Vasoprotectives (VPs) exhibit a wide range of activities beneficial to cardiovascular health. The present study aimed to investigate selected VPs and their structural analogs for their ability to trap MGO/GO, inhibit AGE formation, and evaluate their antioxidant potential. Ultra-high-performance liquid chromatography coupled with an electrospray ionization mass spectrometer (UHPLC-ESI-MS) and diode-array detector (UHPLC-DAD) was used to investigate direct trapping capacity and kinetics of quenching MGO/GO, respectively. Fluorimetric and colorimetric measurements were used to evaluate antiglycation and antioxidant action. All tested substances showed antiglycative effects, but hesperetin was the most effective in RCS scavenging. We demonstrated that rutin, diosmetin, hesperidin, and hesperetin could trap both MGO and GO by forming adducts, whose structures we proposed. MGO-derived AGE formation was inhibited the most by hesperetin, and GO-derived AGEs by diosmetin. High reducing and antiradical activity was confirmed for quercetin, rutin, hesperetin, and calcium dobesilate. Therefore, in addition to other therapeutic applications, some VPs could be potential candidates as antiglycative agents to prevent AGE-related complications of diabetes.

摘要

活性羰基化合物(RCS)如甲基乙二醛(MGO)或乙二醛(GO)是形成晚期糖基化终产物(AGEs)的主要前体。AGEs 是糖尿病血管并发症发展的一个主要因素。血管保护剂(VPs)表现出广泛的有益于心血管健康的活性。本研究旨在研究选定的 VPs 及其结构类似物,以评估它们捕获 MGO/GO 的能力、抑制 AGE 形成的能力,并评估它们的抗氧化潜力。超高效液相色谱-电喷雾电离质谱联用(UHPLC-ESI-MS)和二极管阵列检测器(UHPLC-DAD)分别用于研究直接捕获能力和淬灭 MGO/GO 的动力学。荧光法和比色法用于评估抗糖化和抗氧化作用。所有测试的物质都显示出抗糖化作用,但橙皮素的 RCS 清除效果最有效。我们证明了芦丁、香叶木素、橙皮苷和橙皮素可以通过形成加合物来捕获 MGO 和 GO,我们提出了这些加合物的结构。橙皮素对 MGO 衍生的 AGE 形成的抑制作用最强,而香叶木素对 GO 衍生的 AGEs 的抑制作用最强。槲皮素、芦丁、橙皮素和钙泊三醇具有较高的还原和抗自由基活性。因此,除了其他治疗应用外,一些 VPs 可能是作为抗糖化剂的潜在候选物,以预防糖尿病相关的 AGE 并发症。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2496/8465384/df076c742736/ijms-22-10026-g001.jpg

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