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阐明生物活性蒽醌类化合物对 DNA 晚期糖基化终产物(DNA-AGEs)形成的抑制作用。

Elucidation of inhibitory effects of bioactive anthraquinones towards formation of DNA advanced glycation end products (DNA-AGEs).

机构信息

Department of Chemical and Biological Sciences, National Institute of Technology Meghalaya, Shillong 793003, India.

Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Assam 781039, India.

出版信息

Int J Biol Macromol. 2024 Jun;269(Pt 2):131810. doi: 10.1016/j.ijbiomac.2024.131810. Epub 2024 Apr 26.

Abstract

DNA is essential in biological processes as it directs transcription and translation assisting in RNA and protein synthesis. Extended periods of elevated blood glucose levels cause non-enzymatic DNA glycation, which results in the formation of DNA-AGEs and the production of free radicals, causing structural perturbation of DNA. In this work, we have investigated the glycation of calf thymus (ct-DNA) DNA and examined its inhibition by two anthraquinone derivatives, purpurin and aloin. Ribose sugar served as the glycating agent inducing non-enzymatic glycation of DNA and subsequent DNA-AGEs formation. UV-vis and fluorescence spectroscopic methods were utilized to characterize DNA-AGE formation in vitro. Circular dichroism (CD) spectroscopy was used to observe the structural disruption of DNA caused by glycation. The changes in AGEs fluorescence intensity and melting temperature (T) were measured to assess the inhibition of glycation process by aloin and purpurin. These derivatives demonstrated inhibitory effects via binding to glycating sites of ct-DNA or by scavenging free radicals generated during glycation. The current study elucidates the inhibitory actions of aloin and purpurin on DNA glycation, suggesting their possible applications in mitigating the adverse consequences linked to increased ribose concentrations.

摘要

DNA 在生物过程中至关重要,因为它指导转录和翻译,有助于 RNA 和蛋白质的合成。长期升高的血糖水平会导致非酶促 DNA 糖化,形成 DNA-AGEs 并产生自由基,导致 DNA 结构的扰动。在这项工作中,我们研究了小牛胸腺(ct-DNA)DNA 的糖化,并考察了两种蒽醌衍生物,蒽醌和芦荟素对其的抑制作用。核糖糖作为糖化剂诱导 DNA 的非酶糖化和随后的 DNA-AGEs 形成。利用紫外可见和荧光光谱法对体外 DNA-AGE 的形成进行了表征。圆二色性(CD)光谱用于观察糖化引起的 DNA 结构破坏。通过测量 AGEs 荧光强度和熔点(T)的变化来评估芦荟素和蒽醌对糖化过程的抑制作用。这些衍生物通过与 ct-DNA 的糖化位点结合或清除糖化过程中产生的自由基来表现出抑制作用。本研究阐明了芦荟素和蒽醌对 DNA 糖化的抑制作用,提示它们可能在减轻与核糖浓度升高相关的不利后果方面具有应用潜力。

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